4>EPA
EPA 600
United States
Environmental Protection
Agency
| www.epa.gov/ord
Scientific and Ethical
Approaches for
Observational Exposure Studies
External Review Draft
Office of Research and Development
National Exposure Research Laboratory
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EPA 600/R # TBD
TBD Month YEAR
Scientific and Ethical Approaches for
Observational Exposure Studies
External Review Draft
National Exposure Research Laboratory
Office of Research and Development
U.S. Environmental Protection Agency
Research Triangle Park, NC, 27711
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Notice
This document is a preliminary draft. It has not been formally released by the U.S.
Environmental Protection Agency and should not be construed to represent Agency policy. It is
being circulated for comments on its technical merit and policy implications. Mention of trade
names or commercial products does not constitute endorsement or recommendation for use.
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Abstract
Researchers conduct observational human exposure studies to understand how and the
extent to which people come into contact with pollutants in their everyday lives—through the air
they breathe, the food and liquids they consume, and the things they touch. The U.S.
Environmental Protection Agency's (EPA's) National Exposure Research Laboratory (NERL)
has conducted observational studies for several decades and uses the information and data from
these studies to improve the Agency's understanding of human exposures to chemicals and other
stressors and ultimately to support efforts to improve public health. Because these studies
involve people as research participants, they are complex and raise numerous scientific and
ethical issues that have to be addressed prior to and during their design and implementation. To
ensure that EPA's research continues to be based on the most up-to-date science and the highest
ethical standards, the Agency has developed this document that contains state-of-the-science
approaches for conducting observational human exposure studies. This document is not meant to
represent an official Agency "guidance document," but rather serves as a resource tool and
source of information for NERL and other researchers to rely on as they develop and conduct
observational human exposure studies.
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Foreword
This document is intended as a resource and reference for the U.S. Environmental
Protection Agency's (EPA's) National Exposure Research Laboratory (NERL) scientists as they
develop and implement observational human exposure studies. The authors recognize that this
document also may prove to be useful to others involved in exposure science research, but the
document is not meant to represent an official Agency "guidance document" and should not be
used for that purpose.
Observational studies involve the collection of information about individuals and the
environment around them. NERL scientists and their management team take the protection of
human subjects who participate in their observational studies very seriously. The steps needed to
ensure protection of the human subjects are often complex, and the specific actions will vary
depending on the objectives of the study and details about the participants.
This document does not provide solutions to all scientific and ethical issues that may
arise as such studies are undertaken. That is, it is not possible to identify or address all potential
issues in advance or to develop a comprehensive checklist for all such studies. Rather, this
document attempts to present and discuss the types of i ssues that will need to be considered and
addressed as NERL researchers plan and implement observational human exposure studies. The
researchers will need to work with others—the study team, institutional review board members,
EPA's Human Subjects Research Review Official, the participants and their community, and
other stakeholders—to identify and address all of the relevant issues for their particular study in
order to ensure that the specific elements of the study will respect, safeguard, and protect the
human research subjects.
As EPA employees, NERL scientists face both regulatory and moral obligations to ensure
the protection of the human subjects participating in their observational research. The regulatory
requirements are set forth in EPA's human subjects regulations (40 CFR 26). NERL scientists
are resolved to meet both the "letter" of the law as set forth in the regulations and also the
"spirit" that derives from the most up-to-date thinking and consensus on these sensitive issues.
This document provides information on regulatory requirements and the state of the science for a
number of issues associated with observational human exposure studies to help NERL scientists
meet their goal of conducting observational studies based on the most up-to-date and sound
science and the highest ethical scientific standards.
To gather information for the scientific and ethical approaches for observational human
exposure studies, NERL convened an expert panel workshop on November 28 and 29, 2006, to
discuss state-of-the-science approaches for observational exposure measurement studies. The 11-
member panel discussed their ideas for the content of this document and the state of the science
for various elements of observational exposure studies. The panel agreed that the document
planned by EPA should include the following six major topic areas:
(1) identifying elements to be considered in study conceptualization,
(2) ensuring protection of vulnerable groups,
(3) addressing privacy and other concerns related to personal exposure observational studies,
(4) creating an appropriate relationship between the participant and investigator,
(5) building and maintaining appropriate community and stakeholder relationships, and
(6) designing and implementing strategies for effective communication.
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The structure and content of the current document follow the recommendations of the
Expert Panel. These recommendations include pragmatic steps thatNERL scientists can
undertake during the development and implementation of observational human exposure studies.
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Acknowledgments
This document was developed through the joint efforts of many U.S. Environmental
Protection Agency (EPA) staff. Roy Fortmann, Kent W. Thomas, and Peter Egeghy were
primary authors of the document. Larry Cupitt edited the document and coordinated the reviews.
Linda Sheldon provided extensive input to the development of the document and contributed
through discussions with the authors on issues associated with observational human exposure
studies. Internal EPA reviewers included Pamela Williams, Warren Lux, Michael Firestone,
Gary Bangs, Julian Preston, Hugh Tilson, Ronald Williams, Cathy Fehrenbacher, and Deirdre
Murphy.
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Contents
Notice ii
Abstract iii
Foreword v
Acknowledgments vii
Contents ix
Executive Summary 4-%—- 1
1. Introduction, Purpose, and Scope 9
1.1 Observational Human Exposure Studies 9
1.2 Ethical Issues in Observational Human Exposure Studies 11
1.3 Purpose of This Document 14
1.4 Process for Developing the Document 15
1.5 Organization of the Document 16
1.6 References 17
2. Elements to Be Considered in Study Conceptualization and Planning 19
2.1 Problem Conceptualization 20
2.1.1 Defining the Study Problem 20
2.1.2 Justifying the Study 20
2.2 Planning and Scoping 21
2.2.1 Innovative Study Designs 22
2.2.2 Assessing Benefits and Risks of Study Participation 22
2.2.3 Ensuring That Participant Behaviors Are Not Adversely Changed Because of
Being in the Study 24
2.2.4 Conflicts of Interest (Including Funding) 25
2.3 Study Design 25
2.3.1 Feasibility 26
2.3.1.1 Sample Size Determination 26
2.3.1.2 Quality Assurance Project Plan 27
2.4 Human Subjects Protocol 27
2.5 Independent Scientific and Ethical Review 28
2.5.1 Scientific Peer Review 28
2.5.2 Ethical Review 29
2.6 Internal EPA Review of Scientific and Ethical Issues 30
2.7 Establishing Criteria and Standards for Monitoring Scientific and Ethical Issues
During a Study 30
2.8 References 31
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3. Ensuring Protection of Vulnerable Groups 33
3.1 Identification of Vulnerable Groups 33
3.2 Justification for Involving Vulnerable Persons in Observational Studies 34
3.3 Minimal Risk and Vulnerable Groups 35
3.4 Research Involving Children 35
3.5 Women as Research Subjects 36
3.6 Other Potentially Vulnerable Groups 37
3.7 References 37
4. Privacy, Confidentiality, and Other Concerns Related to Observational Human
Exposure Studies 39
4.1 Privacy Issues 39
4.2 Confidentiality 40
4.2.1 Confidentiality of Information 41
4.2.2 Confidentiality of Participation 42
4.3 Collateral Observations 43
4.3.1 Potential Non-Study Hazards in the Residence 43
4.3.2 Collateral Observations with Mandated Reporting Requirements 43
4.3.3 Hazard Communication 44
4.3.4 Planning and Staff Training 44
4.4 Third-Party Issues 45
4.4.1 Determining Whether a Third Party is a Human Subject 45
4.4.2 Informing Third Parties of Research Activities 46
4.4.3 Research Results and Third Parties 46
4.5 Data and Safety Monitoring and Oversight 46
4.6 References 48
5. Creating an Appropriate Relationship Between the Participant and Researcher
51
5.1 Informed Consent 51
5.1.1 Information 52
5.1.2 Comprehension 54
5.1.3 Voluntary Participation 55
5.2 Payments to Research Participants 56
5.2.1 Regulations and Guidance Regarding Payment to Research Participants...56
5.2.2 Types and Amounts of Incentives or Remuneration Offered in Research
Studies 57
5.2.3 Payments When Children or Other Vulnerable Populations Are Involved ....58
5.2.4 Payments in Observational Human Exposure Studies 60
5.3 Research Rights and Grievance Procedures 61
5.3.1 Ombudsman 61
5.3.2 Community Advisory Board 61
5.4 Creating a Supportive Environment for Research and Interaction 62
5.5 Recruitment Strategies 62
5.6 Retention Strategies 63
5.7 Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk
64
5.8 References 65
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6. Building and Maintaining Appropriate Community and Stakeholder
Relationships 67
6.1 Approaches to Community Involvement 68
6.1.1 Issues in Community Involvement 69
6.1.1.1 Defining "Community." 69
6.1.1.2 Identifying Who Represents the Community 70
6.1.1.3 Building Relationships and Trust 71
6.1.1.4 Importance of Language 72
6.1.1.5 Recognizing and Addressing Cultural Differences 72
6.1.1.6 Honesty, Power Relationships, and Partnerships 72
6.1.1.7 Building a Lasting Infrastructure 73
6.2 Community Involvement and Observational Research 73
6.3 Identifying and Interacting with Other Stakeholders 74
6.4 References 74
6.4.1 Additional Information Resources 76
6.4.2 U.S. Environmental Protection Agency, Office of Environmental Justice
resources: 77
7. Designing and Implementing Strategies for Effective Communication 79
7.1 Communication Strategy and Implementation Plan 79
7.2 Individuals and Groups Involved in the Communications 80
7.3 Communications Timetables—When To Communicate 81
7.4 Communicating at Different Levels 82
7.5 Communications Materials 83
7.6 Educating the Participants and Communities 85
7.7 Reporting Study Results to the Participant and Community 86
7.8 Reporting Unanticipated Results or Observations 88
7.9 Anticipating and Responding to Criticism 90
7.10 Responding to the Media, Public Inquiries, and Other Stakeholders 90
7.11 References 90
7.11.1 Additional Information Resources 91
APPENDIX A 93
APPENDIX B 97
APPENDIX C 101
APPENDIX D List of Acronyms and Abbreviations 103
APPENDIX E Glossary 105
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Executive Summary
Scientists at the U.S. Environmental Protection Agency's (EPA's) National Exposure Re-
search Laboratory (NERL) have conducted observational exposure measurement research for
several decades to understand how people come into contact with chemicals and other stressors
in their everyday lives—through the air they breathe, the food and liquids they consume, and the
things they touch. These studies are performed to determine what chemicals people are exposed
to, the concentrations of the chemicals, the most important sources contributing to people's ex-
posures, the routes and pathways of exposure, and the factors that have the biggest impact on ex-
posure. The studies help explain when, where, why, how, and how often people are exposed to
chemicals in their everyday environments as they go about their daily activities. Information
from these studies helps EPA improve the understanding of people's exposures to chemicals and
other stressors and ultimately supports EPA's efforts to protect public health.
NERL scientists and managers take the protection of human subjects who participate in
their observational studies very seriously. Because observational human exposure studies involve
people as research participants, NERL researchers must act to ensure the protection of the human
subjects throughout the study. Such exposure studies are often complex, and the specific actions
will vary depending on the objectives of the study, the details of the study design and human
subjects research protocol, and the details about the participants and the communities in which
they live. To ensure that the actions of NERL researchers will properly respect, safeguard and
protect the rights and welfare of the participants in their research, NERL scientists need to be
knowledgeable about the scientific and ethical issues that may arise as they plan and conduct
their research, and they also need to be diligent in the application of the most up-to-date and
sound scientific approaches and the highest ethical standards to their research.
This document, therefore, was prepared by NERL scientists as a resource and reference
for EPA's NERL scientists as they develop and implement observational human exposure
studies. The authors recognize that this document also may prove to be useful to others involved
in exposure science research, but the document is not meant to represent an official Agency
"guidance document" and should not be used for that purpose.
As EPA employees, NERL scientists face both regulatory and moral and ethical
obligations to ensure the protection of the human subjects participating in their observational
research. The regulatory requirements are set forth in EPA's human subjects regulations (40 CFR
26). The moral obligations derive from the ethical principles of biomedical ethics. NERL
scientists and managers are resolved to meet both the "letter" of the law as set forth in the
regulations and also the "spirit" that derives from the most up-to-date thinking and consensus on
these sensitive issues.
This document provides information on both the regulatory requirements for the
protection of human subjects and on recent discussions of a number of ethical issues associated
with human subjects research. Knowledge about these requirements and issues will help NERL
scientists meet their goal of conducting observational studies based on the most up-to-date and
sound science and the highest ethical scientific standards.
The ethical and moral issues associated with human subjects research has long been the
subject of a great deal of thought and discussion, both in the U.S. and abroad. Issues in
biomedical ethics continue to be discussed and debated in today's headlines. Spurred by the
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atrocities of World War II concentration camps and by the disclosure of unethical treatment of
undereducated African-American men and other vulnerable groups by medical staff in the United
States, the US and world communities were prompted to establish ethical principles for medical
and scientific experiments that involve people as participants. In the United States, the Belmont
Report (DHEW, 1979) is the foundational document in the development of the ethics of human
subjects. This report lays out the fundamental ethical principles behind research that involves
humans as research subjects. These three basic principles, (1) respect for persons, (2)
beneficence, and (3) justice, have become the cornerstones for regulations involving human
subjects. Ethicists have expanded on those principles since 1979, translating them into ethical
requirements that any human subjects research must be both ethically acceptable and
scientifically sound.1 EPA's Science Advisory Board has affirmed, "Bad science is always
unethical" (U.S. EPA, 2000).
In an effort to ensure that NERL's observational human exposure studies are founded on
the ethical principles of respect for persons, beneficence and nonmaleficence, and justice and
adhering to the principle that bad science is always unethical, scientists and managers from
NERL have assembled this document as a resource and reference for NERL exposure scientists.
These same scientists and managers have sought expert advice, including input from an expert
panel workshop, and have prepared this external review draft of the document to seek both
external peer review, and public input about the state of the sci ence in regard to observational
exposure studies and their ethical implementation.
A number of references, both from the bioethics literature and from U.S. regulations,
have proven useful to the authors as they have developed this document. Those references are
listed in Table 1-4, which is replicated below.
Table 1-4. Important References in Developing This Document:
Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants
Year
Event/Report
Description
1979
The Belmont Report:
Ethical Principles and
Guidelines for the
Protection of Human jr%
Subjects of Research % A.
(DHEW, 1979) ^
The Belmont Report attempts to summarize the basic ethical principles identified by the
legislatively created National Commission for the Protection of Human Subjects of
/BftTieaical and Behavioral Research. It is a statement of basic ethical principles and
guidelines that should assist in resolving the ethical problems that surround the conduct of
¦yjgsearch with human subjects. The three basic ethical principles are (1) respect for persons,
(2) beneficence, and (3) justice.
1991
The Common Rule ;
40 CFR 26^luB^aH A
The Common Rule is a short name for "The Federal Policy for the Protection of Human
Subjects" and was adopted by more than a dozen Federal departments or agencies in 1991.
Each agency incorporated the policy into its own Code of Federal Regulations (CFR), with
EPA adapting it in Title 40 CFR Part 26 Subpart A.
1993
The Institutional Review
Guidebook (HHS, 1993)
The document is intended as a resource and a reference document for IRB members,
researchers, and institutional administrators. It is not designed to tell IRBs whether or not
specific protocols should be approved, rather the Guidebook points out issues to which IRBs
should pay attention and presents, wherever possible, areas where ethicists have arrived at
a consensus on the ethical acceptability of a particular activity or method.
2000
What Makes Clinical
Research Ethical?
(Emanuel et al., 2000)
This journal article lays out seven areas of concern that need to be addressed if clinical
research is deemed to be ethically acceptable: (1) social or scientific value, (2) scientific
validity, (3) fair subject selection, (4) favorable risk-benefit ratio, (5) independent review, (6)
informed consent, and (7) respect for potential and enrolled subjects.
1 See, for example, the writings of Beauchamp and Childress in Principles of Biomedical Ethics (Beauchamp and
Childress, 2001) and the discussion of "What Makes Clinical Research Ethical?" by Emanuel, Wendler, and Grady
(Emanuel et al., 2000).
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Table 1-4. Important References in Developing This Document:
Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants
Year
Event/Report
Description
2001
Principles of Biomedical
Ethics (Fifth Edition)
(Beauchamp and
Childress, 2001)
A classic text in biomedical ethics. Core chapters discuss respect for autonomy,
nonmaleficence, beneficence, and justice. The chapter on Professional-Patient
Relationships discusses issues important to privacy, confidentiality, and protection of
subjects. The fifth edition is an update that reflects developments in philosophical analysis
as well as developments in science and medicine.
2002
International Ethical
Guidelines for Biomedical
Research Involving Human
Subjects (CIOMS, 2002),
Developed by the Council for International Organizations of Medical Sciences pattictilarlylfor
use in developing countries, the guidelines relate mainly to ethical justification and scientific
validity of research; ethical review; informed consent; vulnerability of individual^, groups,
communities, and populations; women as research subjects; equity regarding burdens and
benefits; choice of control in clinical trials; confidentiality; compensation for injury:
strengthening of national or local capacity for ethical review; and obligations of sponsors to
provide health care services.
2003
Protecting Participants and
Facilitating Social and
Behavioral Sciences
Research (NRC, 2003),
This NRC publication targets policymakers, research administrators, research sponsors, IRB
members, and investigators. It examines three key ethical issues: (1) obtaining informed,
voluntary consent from prospective participants; (2) guaranteeing the confidentiality of
information collected from participants, which is a particularly challenging problem in social
sciences research; and (3) using appropriate review procedures for minimal-risk research.
2005
Ethical Considerations for
Research on Housing-
Related Health Hazards
Involving Children, (NRC &
IOM, 2005)
This National Research Council and Institute of Medicine report reviews the challenges and
ethical issues in conducting housing-related health hazards research in the wake of the
Maryland Court of Appeals ruling in the case of Grimes v. Kennedy Krieger Institute that has
led to substantial controversy and eonfusion. The ruling highlighted a range of potential
ethical concerns, such as issues involving adequacy of informed consent, parents'
perception of risk, duties of researchers to child subjects and their parents, the role of IRBs,
and the authority of parents to provide permission for their children to participate in
research. This report offers much needed recommendations and practical guidance for the
ethical conduct of this type of research.
2006
EPA adds Additional
Human Subjects
protections at 40 CFR 26
EPA added additional human subjects protections in the Code of Federal Regulations to
govern its actions. Subparts B-D apply to research conducted or supported by EPA and are
directly applicable to NERL and this document. Subpart B prohibits research involving
intentional exposure of children, pregnant women (and their fetuses), or nursing women.
Subparts C and D provide additional protections for observational research involving
pregnlnt%omen and their fetuses (Subpart C) and for children (Subpart D). Subparts K-M
and O-Q apply to EPA's use of third-party human research data.
2007
International Ethical ^ J
Guidelines for
Epidemiological Research
(CIOMS, 2007)
This document builds on the CIOMS (2002) document (see above) and extends the
Siscussion to address the special features of epidemiological studies.
The authors also have relied extensively on the advice of an expert panel that came
together in November 2006 to provide advice and guidance about the structure and content of
this document. The expert panel consisted of 11 nationally recognized authorities in a diversity
of fields—exposure science, bioethics, epidemiology environmental health, law, community-
based research, community liaison, research in minority communities, public health, toxicology,
pediatrics, children's environmental health, etc.
The Expert Panel Workshop resulted in suggestions for both the structure and the content
of this document (ERG, 2007). Following the advice of the expert panel, this document is
organized in seven sections.
Section 1. Introduction: This section lays out the background for observational exposure
research, the scope of the document, and some of the important scientific and ethical issues
that are critical to human subjects and observational exposure research.
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Section 2. Elements to be considered in study conceptualization: This section establishes that
ethical concerns are to be incorporated in the scientific effort from the very start and should be
an integral element of all phases of study planning and implementation. Development of the
appropriate scientific and ethical approaches begins with study conceptualization, scoping, and
planning and continues throughout the study. As shown in the Figure 2-1 (included here), the
planning process involves the initial identification of the research question and justification of
the research during the problem conceptualization
phase. If human subjects research can be justified
for the study, the scientific and ethical approaches
are developed and described in the study design and
the human subjects research protocol. This
document describes how these approaches must be
integrated and harmonized. It is suggested that, to
the extent possible, researchers consider alternative
and innovative study designs that address the
research question and maximize the benefits to the
study participants and their community.
The document describes the basic elements that
should be included in the study design and in the
human subjects research protocol. Information is
provided to researchers on both scientific peer
review and ethical review and how they are to be
considered together. EPA researchers follow
specific procedures mandated by EPA Order
1000.17A1 and other policies. These include both external peer review and review by
Institutional Review Boards (IRBs), and Agency review by the EPA Human Subjects Research
Review Official (HSRRO).
Section 3. Ensuring protection of vulnerable groups: This section discusses some of the special
protections afforded to vulnerable groups by EPA's human subjects rules and the ethical issues
of involving such groups in observational exposure studies. Researchers need to be cognizant
of speci al requirements and concerns for protection of vulnerable groups throughout the
planning and implementation of these studies. Potentially vulnerable groups include children,
prisoners, pregnant women, handicapped persons, mentally disabled persons, and
economically or educationally disadvantaged persons.
Section 4. Addressing privacy and other concerns related to personal exposure observational
studies: This section lays out the ethical issues and the regulatory requirements, including
observations of nonstudy hazards and the recently discussed issues of third-party involvement
and concerns. NERL's observational human exposure studies are designed to describe people's
contact with chemicals as they go about their every-day lives. Unlike clinical research that
may be conducted in a research facility or institutional setting, observational studies, of
necessity, take place in the participants' "personal" environment—their home, daycare center,
school, vehicle, workplace, and other locations that participants often consider to be personal
and private. This difference in the research setting means that researchers involved in
observational human exposure studies have an even greater challenge in meeting the ethical
obligation to respect the privacy of the participants.
Another important concern is the development of approaches and procedures for dealing
with potential non-study hazards. Research staff may observe potential hazards unrelated to
the research being performed. Examples of potential hazards that might be encountered in a
residential environment include unsecured firearms, unprotected stairways, malfunctioning or
un-vented combustion appliances, unsecured poisons or other dangerous products, and
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Figure 2-1: Stages tn ttie Development of a NERL
Observational Human Exposure Study
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excessive mold growth. The NRC & IOM (2005) report recommends that researchers should
consider such foreseeable observations and potential hazards in advance, develop responses to
the risks, and submit the proposed plans to the IRB for review to ensure that they are
appropriate "in the context of the research and the affected community."
This section also discusses third party issues that can arise in observational studies if (1) the
study collects limited information about or related to individuals other than the study
participants or (2) study activities affect or involve people or organizations other than the study
participants. Third parties could potentially include household members not enrolled in the
study, relatives, members of the community, landlords, etc. Researchers need to be aware of
the potential impact of study activities on third parties and need take third party issues into
account in study planning, IRB review, and communications during all phases of a study
Section 5. Creating an appropriate relationship between participant and investigator: This
section builds on the ethical principles of respect for persons and beneficence to di scuss the
issues around recruitment, informed consent, compensation, and the researcher's need to
support the welfare of the participants. An appropriate relationship must be built on openness
and trust and requires strong and effective bi-directional communication. One of the key
elements is the informed consent process. Informed consent ensures that the participant
understands the range of risks associated with participation and the voluntary nature of
participation, and provides essential protections to the participant. Approaches related to three
"pillars" of informed consent: (1) information, (2) comprehension, and (3) voluntary
participation, are discussed. Compensation of research participants is a very sensitive issue.
The decision whether to remunerate research participants, and the appropriate level of
compensation, is a complex ethical issue, balancing the issue of fairness against the possibility
of undue influence and the loss of free consent. There is little specific guidance regarding
remuneration in Federal human research regulations. This document discusses the recent
observations by various national and international review committees and identifies resources
that researchers can review during consideration of this complex issue. Other topics include
participant recruitment, retention strategies, and research rights and grievance procedures.
Section 6. Building and maintaining appropriate community and stakeholder relationships: The
need to involve the community and stakeholders derives from the principles of fairness,
justice, and equity and of respect for persons. Involving the community in the research effort
can be expected to benefit the community, benefit the research team, and improve the research
both scientifically and ethically. The process of community involvement should be an on-
going process of effective two-way communication that is initiated at the very earliest stages
of study conceptualization and planning. This relationship must also be built on honesty,
openness, and trust. Various approaches are discussed related to issues such as defining the
community, identifying who represents the community, recognizing and addressing cultural
differences, and the importance of language, power relationships, and partnerships.
Section 7. Designing and implementing strategies for effective communication: The discussion
builds on the presumption of an ongoing, interactive dialogue and exchange of ideas between
researchers and participants, community, and stakeholders, and the public, and this final
section focuses on steps that the researcher needs to take for effective communications. The
ethical principle of respect for persons, including respect for one another's autonomy and
welfare, demands that researchers, participants, community members, and stakeholders strive
to establish effective communications and to foster a relationship of trust and respect. The
researchers should make a commitment to effective communications and make the appropriate
investment of time and resources to ensure that the communications are at an appropriate level
and are truly effective. Although it is recognized that the key to effective communication is bi-
directional, much of the focus of the discussion in this document is from the perspective of in-
formation dissemination to participants, communities, and stakeholders. To that end the
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document describes communication strategies, implementation plans, communication groups,
timetables, communication materials, and other tools available to researchers. The document
also discusses issues associated with communication of results to study participants and
communities.
This document does not—indeed, could not—provide solutions to all scientific and
ethical issues that may arise as observational studies are undertaken. No document could identify
and address all potential issues in advance, nor is it possible to develop a comprehensive
checklist for all such studies. Rather, this document attempts to present and discuss the types of
ethical and scientific issues that will need to be considered and addressed as NERL researchers
plan and implement observational human exposure studies. The researchers will need to work
with others—the study team, institutional review board members, EPA's Human Subjects
Research Review Official, the participants and their community, and other stakeholders—to
identify and address all of the relevant issues for any particular study. The authors are confident
that this document will be helpful to NERL scientists in their endeavors to assure that all of
NERL's observational human exposure research will respect, safeguard, and protect the
participants in that research.
References
Beauchamp TL, Childress, JF (2001). Principles of Biomedical Ethics: Fifth Edition. New York, NY: Oxford
University Press.
CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection
of Human Subjects. U.S. Code of Federal Regulations. Available:
http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06.hlml |acccssed 12 June 2007],
CIOMS (The Council for International Organizations of Medical Sciences) (2007). International Ethical Guidelines
for Epidemiological Research (Discussion Draft No. 3. April 2007). World Health Organization. Geneva,
Switzerland. Available: http://www.cioms.cli/070516april_cpi_rcvisions.pdf [accessed 12 June 2007],
CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines
for Biomedical Research Involving Humajt Subjects. World Health Organization. Geneva, Switzerland. Available:
http://www.cioms.ch/frame_guidclincs_nov_2002.htm [accessed 12 June 2007],
Emanuel EJ, WendlerD. Grady C (2000). What Makes Clinical Research Ethical? JAMA 20:2701-2711.
ERG (Eastern Research Group) (2007). Report on the Workshop to Discuss State-of-the-Science Approaches for
Observational Exposure Measurement Studies. Final Report: January 25, 2007.
NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
Research. Washington, DC: The National Academies Press. Available:
http://books.nap.cdu/catalog.php?record_id=10638 [accessed 12 June 2007],
NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
Housing-Related Health Hazards Involving Children. Committee on Ethical Issues in Housing-Related Health
Hazard Research Involving Children, Youth and Families, Bernard Lo and Mary Ellen O'Connell (eds). Board on
Children, Youth, and Families, Division of Behavioral and Social Sciences and Education and Institute of Medicine.
Washington, DC: The National Academies Press. 216 pp. Available at
http://books.nap.edu/catalog.php?record_id=11450 [accessed 12 June 2007],
U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles
and Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of
Human Subjects of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html
[accessed 12 June 2007],
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1 U.S. EPA (U.S. Environmental Protection Agency) (2000) Comments on the Use of Data from the Testing of Human
2 Subjects: A Report by the Science Advisory Board and the FIFRA Scientific Advisory Panel. United States
3 Environmental Protection Agency, Science Advisory Board, EPA-SAB-EC—017.
4
5 U.S. HHS (U.S. Department of Health and Human Services) (1993). The Institutional Review Guidebook. Office for
6 Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm [accessed 12 June 2007],
7
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SECTION 1
Introduction, Purpose, and Scope
Observational human exposure studies are an important research tool for understanding
people's contact with pollutants and other stressors in the environment—their exposure.2 Such
studies allow researchers to collect information about people's exposures to chemicals under
real-world conditions during their normal day-to-day activities. Exposures occur through the air
we breathe, the food we eat, the water and beverages we drink, and the surfaces that we touch as
we go about our daily routines. To understand and characterize people's exposures to chemicals,
two things have to be known: (1) the concentrations of the chemicals in the environment that
people inhale, ingest, or touch; and (2) the human activities that bring people into contact with
the media containing the chemicals.3 This document addresses issues associated with
observational human exposure studies as conducted by the U.S. Environmental Protection
Agency's (EPA's) National Exposure Research Laboratory (NERL), in an effort to understand
and characterize the exposures that people encounter as they go about their daily lives.
Because observational human exposure studies involve human participants, they are
complex in their design and implementation. As in all research involving human participants,
observational human exposure studies carry both regulatory obligations for the protection of
human subjects (40 CFR 26) and ethical obligations to the study participants: namely to respect
their autonomy, not to inflict harm (nonmaleficence), to avoid harm and to maximize their
benefits (beneficence), and to treat all participants fairly (justice). (See, for example, Principles
of Biomedical Ethics (Beauchamp and Childress, 2001). Ethical obligations have to be carefully
considered as they relate to the scientific elements of these studies. Therefore, it is important that
researchers recognize and understand these obligations and use the most up-to-date scientific and
ethical approaches in the design and implementation of observational human exposure studies.
1.1 Observational Human Exposure Studies
Observational human exposure studies differ in a very fundamental way from intentional
exposure studies.4 The studies being addressed in this document are "observational" in that they
involve only the collection of environmental samples, data, and information from study
participants and their everyday environments as they go about their normal activities. These
studies do noI involve intentional exposure of the participants, nor do these studies involve some
manipulation of a person's behavior or of his or her environmental conditions in an attempt to
impact the participant's exposure. In developing this document, NERL held an expert panel
2 Exposure, as it is used throughout this document, is a technical term that is defined as the "contact of a chemical,
physical, or biological agent with the outer boundary of an organism [e.g., a person]. Exposure is quantified as the
concentration of the agent in the medium in contact integrated over the time duration of that contact." (The
definition is taken from Guidelines for Exposure Assessment [EPA/600/Z-92/001, May 1992]). See the Glossary for
more information and the definition of additional terms.
3 The term "chemical" is used in this document as a surrogate term for all stressors, including chemical, physical, or
biological agents.
4 EPA has defined observational research and intentional exposure of a human subject in the Agency's Human
Subjects rules (40 CFR 26 Subparts B and C). "Research involving intentional exposure of a human subject means a
study of a substance in which the exposure to the substance experienced by a human subject participating in the
study would not have occurred but for the human subject's participation in the study" [40 CFR 26.202(a)]. The
regulations also state that"observational research means any human research that does not meet the definition of
research involving intentional exposure of a human subject' (40 CFR 26.302).
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workshop to identify the content and organization of this document (ERG, 2007). The expert
panel recommended that the scope of this document be limited to observational human exposure
measurement studies.
Observational studies are performed for many different purposes. They have been used
extensively in the fields of social behavioral, economic, biological, medical, epidemiological,
and exposure research to collect information that relates one or more variables (e.g., exposure to
a chemical) to its result (e.g., the concentration of an exposure biomarker in blood). There are
many examples of observational human exposure studies that have been conducted over the last
decade, and the reader is referred to the Journal of Exposure Science and Environmental
Epidemiology and to Environmental Health Perspectives for examples of the objectives, designs,
and results of observational studies. NERL researchers have conducted and relied on
observational studies for more than three decades. Common goals in those studies included those
that follow.
• Identify which chemicals or other stressors that people are exposed to during their normal
activities in the environments that they occupy.
• Measure the concentrations of the
chemicals to which they are
exposed.
• Identify the most important routes
and pathways of exposure.
• Identify the factors that impact
people's exposures (i.e., determine
the when, why, how, and how
much that people are exposed to
chemicals in the environment).
These studies involve many
different types of data collection
efforts and typically include
observations, measurements, and
information on the following
subjects.
• Chemical concentrations in
environmental media (air, water,
soil, floor dust, and dust on
surfaces)
• Chemical concentrations in the
diet (food and beverages)
• Biomonitoring (measurements of
biomarkers of exposure in urine,
blood and saliva)
• Time/location/activity information
• Information on personal activities,
product use, diet, occupation, and
other factors that may impact
exposure
• Information on the characteristics
of the environments that study
participants occupy (homes,
schools, offices, public access
buildings, etc.)
Table 1-1. Examples of the Impact of Observational Human
Studies on Pollution Levels and Regulatory Actions
Pollutant
Observational
Study Result
Impact/Action/Result
Particulate
Matter (PM)
Observational
panel studies
Sfemtuistrated the
appropriateness
of ambient
measurement of
fine particles as a
surrogate for a
population's
longitudinal
exposure to fine
PM.
Resolved questions in NAS review of
PM science and provided a "generally
consistent finding that ambient
particle concentrations are a key
determinant of the longitudinal
variation in personal exposure."
(NRC, 2004). These results have
been instrumental in support of the
National Ambient Air Quality Standard
for PM (U.S.EPA, 2004).
Volatile
Organic
Compounds
(VOCs)
EPA's Total
Exposure
Assessment
Methodology
(TEAM) studies
found levels of
about a dozen
common organic
pollutants to be 2
to 5 times higher
inside homes
than outside. Use
of products
containing
organic
chemicals may
result in very high
and persistent
pollutant levels.
EPA, States, and the Consumer
Product Safety Commission worked
together to influence manufacturers to
voluntarily reduce emissions of toxic
chemicals from consumer products,
building materials, and furnishings,
and to develop mitigation strategies
and educational materials to teach
people how to reduce their contact
with chemicals indoors. As a result,
contact with toxic chemicals indoors
has been reduced (see
www.cpsc.gov/CPSCPUB/PUBS/450.
html).
Formaldehyde
Observational
studies found
elevated
formaldehyde
levels indoors
and helped
identify indoor
sources.
EPA worked with HUD, CPSC, and
other agencies to limit formaldehyde
in building or consumer products and
to educate the public on how to
reduce exposures (see
www.epa.gov/iaq/formalde.html).
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The information obtained in observational human exposure studies is used to better
understand people's contact with chemicals in the environment and to improve exposure
assessments and risk assessments. This information is also essential for developing risk
mitigation strategies and for developing educational materials and programs for reducing
exposures and risks to chemicals or other stressors in the environment (see Table 1-1).
1.2 Ethical Issues in Observational Human Exposure Studies
By definition, observational human exposure studies involve human subjects. Whenever
their research involves human subjects, EPA researchers are required to ensure the protection of
the study participants by complying with the Agency's human subjects rules as set forth in
40 CFR 26.
The Common Rule (Subpart A of the rules) represents basic regulatory actions (common
to more than a dozen Federal departments or agencies) that are intended to ensure the protection
of all human subjects. The central requirements of the Common Rule are (1) that people who
participate as subjects in covered research are selected equitably and give their fully informed,
fully voluntary written consent; and (2) that proposed research be reviewed by an independent
oversight group referred to as an institutional review board (IRB) and approved only if risks to
subjects have been minimized and are reasonable in relation to anticipated benefits, if any, to the
subjects and the importance of the knowledge that may reasonably be expected to result.
EPA has adopted additional protections for children and pregnant or nursing mothers in
Subparts B through D. These sections apply to all research either conducted or funded by EPA
and are, therefore, directly applicable to NERL's observational human exposure research.5
Subpart B prohibits EPA from conducting or supporting research that involves intentional
exposure of "a pregnant woman (and, thereby, her fetus), a nursing woman, or a child." NERL
researchers conducting (or funding) observational human exposure research studies must comply
with all of these regulatory requirements, including seeking review and approval by an IRB and
by the Agency's Human Subjects Research Review Official (HSRRO) before beginning any
human subjects research. EPA's human subjects rules also define a variety of fundamental
terms—from "human subject" to "research" to "intentional exposure" to "observational
research." Understanding these regulatory definitions is vital for NERL researchers to comply
with the regulatory requirements.6
To more effectively ensure the protection of human subjects, NERL scientists and
managers need to understand the ethical principles and issues that prompted the development of
the regulatory requirements in the first place and to be knowledgeable about the most recent
thinking and guidance on protection of human subjects.
The Belmont Report (U.S. DHEW, 1979) is a foundational document in the development
of the ethics of human subjects research in the United States. Because of the adverse publicity
and political embarrassment arising from the unethical treatment of African-American men in the
Tuskegee Syphilis Study, Congress passed the National Research Act of 1974, which called on
the Department of Health, Education and Welfare to codify its rules on human subjects research
and established the National Commission for the Protection of Human Subjects of Biomedical
and Behavioral Research. The Commission was charged with identifying the basic ethical
principles that should underlie human subjects research. The Commission published the Belmont
5 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements that have to be met if human subjects
data from a person or group external to EPA and not funded by EPA (a third party) are to be used by EPA in
specified rulemaking actions. These subparts do not apply to NERL researchers and will not be discussed further in
this document.
6 The Glossary lists definitions for a number of important terms; definitions that come from the regulatory language
are identified with their specific CFR citation.
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Report in 1979. This report established three
basic principles, (1) respect for persons,
(2) beneficence, and (3) justice, which have
become the cornerstones for regulations
involving human subjects (see Table 1-2).
In 1981, the Department of Health and
Human Services (HHS) issued regulations
based on the Belmont Report. Ten years later,
the core HHS regulations (Subpart A) were
adopted by almost all of the Federal
departments and agencies that conducted or
sponsored human subjects research as the
"Common Rule."
Since 1991, ethical thought and
regulatory processes for the protection of
human subjects have continued to evolve and
grow. For example, many ethicists expand the
elements contained in the principle of
beneficence from the Belmont Report into two
principles: (1) beneficence, meaning to prevent or remove harm and to maximize the possible
benefits; and (2) nonmaleficence, meaning not to inflict harm (Beauchamp and Childress, 2001).
In 2000, Emanuel,
Wendler, and Grady considered
the ethical principles involved in
clinical research and proposed
seven ethical requirements to be
addressed in research with
humans (Emanuel et al., 2000).
Their published article specifically
addressed clinical research, but
the issues are similar for
observational human exposure
research. Their ethical
requirements are summarized and
briefly explained in Table 1-3.
The requirements are a logical
extension of the ethical principles
enunciated in the Belmont Report
and manifest themselves in
additional requirements for social
or scientific value; for processes
to ensure the scientific integrity of
the research; and for independent
review of the design, the subject
population, and the risk/benefit
ratio. The principle of respect for
subjects also includes additional
emphasis on the welfare of the
subjects.
Table 1-2. The Belmont Report:
Principles and Recommendations
Ethical Principle
Regulatory Manifestation
Respect for Persons
• Individuals should be
treated as autonomous
agents.
• Persons with
diminished autonomy
are entitled to
protection.
Informed Consent
• Subjects must be given
opportunity to choose what will
or will not happen to them
• The consent process must
include (1) information, (2)
comprehension, and (3)
voluntariness
Beneficence
• Human subjects should
not be harmed.
• Research should
maximize possible
benefits and minimize
possible harms.
Assessment of Risks and
Benefits
• The nature and scope of risks
and benefits must be assessed
in a systematic manner.
Justice
• The benefits and risks
of research must be
distributed fairly.
Selection of Subjects
/• Tftefe' must be fair procedures
and outcomes in the selection of
'research subjects.
Table 1-3. Seven Ethical Requirements for Clinical Research
From Emanuel, Wendler, and Grady (2000)
Requirement
Explanation
Social or
scientific value
Evaluation of a treatment, intervention, or theory that will
improve health and well-being or increase knowledge
Scientific
> validity
Use of accepted scientific principles and methods, including
statistical techniques, to produce reliable and valid data
Fair subject
selection
Selection of subjects so that stigmatized and vulnerable
individuals are not targeted for risky research, and the rich
and socially powerful are not favored for potentially beneficial
research
Favorable risk-
benefit ratio
Minimization of risks; enhancement of potential benefits and
risks to the subject are proportionate to the benefits to the
subject and to society.
Independent
review
Review of the design of the research trial, its proposed
subject population, and risk/benefit ratio by individuals
unaffiliated with the research
Informed
consent
Provision of information to subjects about the purpose of the
research, its procedures, potential risks, benefits, and
alternatives, so that the individual understands this
information and can make a voluntary decision whether to
enroll and continue to participate
Respect for
potential and
enrolled
subjects
Respect for subjects by
• permitting withdrawal from the research,
• protecting privacy through confidentiality,
• informing subjects of newly discovered risks or benefits,
• informing subjects of results of the research, and
• maintaining welfare of subjects.
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More recently, there has been increased scrutiny and discussions of the ethics of research
involving human participants,7 and a number of respected institutions have addressed many
important scientific and ethical issues on this topic, including the National Research Council in
its report, Protecting Participants and Facilitating Social and Behavioral Sciences Research
(NRC, 2003), a joint National Research Council and Institute of Medicine (NRC & IOM, 2005)
committee in the report on Ethical Considerations for Research on Housing-Related Health
Hazards Involving Children, the Council for International Organizations of Medical Sciences
(CIOMS) under the World Health Organization in its International Ethical Guidelines for
Biomedical Research Involving Human Subjects (CIOMS, 2002) and in the International Ethical
Guidelines for Epidemiological Research (CIOMS, 2007), and others.
Collectively, these documents have reaffirmed the basic ethical principles asserted in the
Belmont Report and have attempted, in some cases, to expand scientific and ethical reasoning
and understanding to define approaches for dealing with additional elements of human subjects
research. These additional elements, which often have been identified because of specific
incidents or case studies, include issues such as those described below.
• Compensation to participants—How much is adequate and fair, without being an undue
inducement?
• Non-study hazards—What is the researcher's responsibility to identify hazards in the home
that are not part of the study?
• Third-party issues—Are there people other than the participant who may be impacted during
the study and by the study results?
• Community involvement—How should the community be involved in the design and
implementation of studies?
These documents, together with the EPA's regulatory requirements for the protection of human
subjects, serve as important references for the subsequent sections of this document (see Table 1-
4).
Table 1-4. Important References in Developing This Document:
Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants
Year
Event/Report
Description
1979
The Belmont Report: %
Ethical Principles arid
Guidelines for the
Protection of Human
Subjects of Research
(DHEW, 1
The Belmont Report attempts to summarize the basic ethical principles identified by the
legislatively created National Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research. It is a statement of basic ethical principles and
guidelines that should assist in resolving the ethical problems that surround the conduct of
research with human subjects. The three basic ethical principles are (1) respect for persons,
(2) beneficence, and (3) justice.
1991
The Common Rule
26, Subpart A
The Common Rule is a short name for "The Federal Policy for the Protection of Human
Subjects" and was adopted by more than a dozen Federal departments or agencies in 1991.
Each agency incorporated the policy into its own Code of Federal Regulations (CFR), with
EPA adapting it in Title 40 CFR Part 26 Subpart A.
1993
The Institutional Review
Guidebook (HHS, 1993)
The document is intended as a resource and a reference document for IRB members,
researchers, and institutional administrators. It is not designed to tell IRBs whether or not
specific protocols should be approved, rather the Guidebook points out issues to which IRBs
should pay attention and presents, wherever possible, areas where ethicists have arrived at
a consensus on the ethical acceptability of a particular activity or method.
7 The term "human participants" often is used in this document. It denotes the importance of the study participant
being actively engaged in a partnership with the researchers to address the objectives and goals of the study. The
term should be considered to be synonymous with the term "human subject" as used in the Common Rule and in
documents used to describe regulatory requirements for studies involving human subjects.
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Table 1-4. Important References in Developing This Document:
Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants
Year
Event/Report
Description
2000
What Makes Clinical
Research Ethical?
(Emanuel et al., 2000)
This journal article lays out seven areas of concern that need to be addressed if clinical
research is deemed to be ethically acceptable: (1) social or scientific value, (2) scientific
validity, (3) fair subject selection, (4) favorable risk-benefit ratio, (5) independent review, (6)
informed consent, and (7) respect for potential and enrolled subjects.
2001
Principles of Biomedical
Ethics (Fifth Edition)
(Beauchamp and
Childress, 2001)
A classic text in biomedical ethics. Core chapters discuss respect for autonomy,
nonmaleficence, beneficence, and justice. The chapter on Professional-Patient
Relationships discusses issues important to privacy, confidentiality, and protection of
subjects. The fifth edition is an update that reflects developments in philosophical analysis
as well as developments in science and medicine.
2002
International Ethical
Guidelines for Biomedical
Research Involving Human
Subjects (CIOMS, 2002),
Developed by the Council for International Organizations of Medical Sciences particularly for
use in developing countries, the guidelines relate mainly to ethical justificatioti and scientific
validity of research; ethical review; informed consent; vulnerability ?of individuals, groups,
communities, and populations; women as research subjects; equity regarding burdens and
benefits; choice of control in clinical trials; confidentiality; compensation for injury;
strengthening of national or local capacity for ethical review; and obligations of sponsors to
provide health care services.
2003
Protecting Participants and
Facilitating Social and
Behavioral Sciences
Research (NRC, 2003),
This NRC publication targets policymakers, research administrators, research sponsors, IRB
members, and investigators. It examines three key ethical issues: (1) obtaining informed,
voluntary consent from prospective participants; (2) guaranteeing the confidentiality of
information collected from participants, which is a particularly challenging problem in social
sciences research; and (3) using appropriate review procedures for minimal-risk research.
2005
Ethical Considerations for
Research on Housing-
Related Health Hazards
Involving Children, (NRC &
IOM, 2005)
This National Research Council and Institute of Medicine report reviews the challenges and
ethical issues in conducting housing-related health hazards research in the wake of the
Maryland Court of Appeals ruling in the case of Grimes v. Kennedy Krieger Institute that has
led to substantial controversy and confusion. The ruling highlighted a range of potential
ethical concerns, such as issues involving adequacy of informed consent, parents'
perception of risk; duties of researchers to child subjects and their parents, the role of IRBs,
and the authority of parents to provide permission for their children to participate in
research. This report offers much needed recommendations and practical guidance for the
ethical conduct of this type of research.
2006
EPA adds Additional
Human Subjects
protections at 40 CFR 2®<^
EPA added additional human subjects protections in the Code of Federal Regulations to
govern its actions. Subparts B-D apply to research conducted or supported by EPA and are
directly applicable to NERL and this document. Subpart B prohibits research involving
intentional exposure of children, pregnant women (and their fetuses), or nursing women.
Subparts C and D provide additional protections for observational research involving
pregnant women and their fetuses (Subpart C) and for children (Subpart D). Subparts K-M
and O-Q apply to EPA's use of third-party human research data.
2007
International Ethical
Guidelines for
Epidemiological Research
(CIOMS, 20d7)
This document builds on the CIOMS (2002) document (see above) and extends the
discussion to address the special features of epidemiological studies.
1.3 Purpose of This Document
This document is meant to serve as a resource of current scientific and ethical
information for NERL researchers as they develop and conduct observational human exposure
studies. The increased scrutiny of research studies involving human participants makes it
imperative that researchers ensure that their research protocols for protection of human subjects
in observational human exposure studies incorporate the most up-to-date ethical approaches.
Protocols for protecting study participants in research studies have been developed by experts in
both academia and various Federal agencies and adopted by the research community because
they ensure that observational studies meet the highest ethical and scientific standards. However,
because ethical and scientific approaches for human subjects research continue to be refined and
evolve over time, there is a continuing need to evaluate the latest approaches and ensure that
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researchers are using state-of-the-science approaches in their design and implementation of such
studies.
The purpose of this document is to provide information that researchers in EPA's Office
of Research and Development's NERL can use in the design and implementation of
observational human exposure studies to ensure the protection of the human study participants. It
is intended to be a resource tool for NERL's exposure science researchers, but it is not intended
to serve as a "guidelines" document or a "how-to" checklist. The authors have tried to (1)
identify major areas and elements of observational studies for which ethical issues need to be
considered, (2) provide information on the state of the science for selected approaches for
applying ethical principles to the conduct of these studies, and (3) provide sources of information
that researchers can use in the design and implementation of observational human exposure
studies.
This document does not provide solutions to all scientific and ethical issues that may
arise as such studies are undertaken. That is, it is not possible to identify or address all potential
issues in advance or develop a comprehensive checklist for all such studies. Rather, this
document attempts to present and discuss the types of issues that will need to be considered and
addressed as NERL researchers plan and implement observational human exposure studies. The
researchers will need to work with others—the study team, IRB members, EPA HSRRO, the
participants and their community, and other stakeholders—to identify and address all of the
relevant issues for their particular study to ensure that the specific elements of the study will
safeguard and protect the human research subjects.
In addition to being an information resource for NERL researchers, contractors and
grantees funded by NERL will be expected to consider and be familiar with the approaches
presented in this document in the design and implementation of their exposure science research.
Although not its intended audience, this document also may prove to be useful to other
researchers, within and outside of EPA, who are involved in observational human exposure
research.
1.4 Process for Developing the Document
This document was written by exposure science researchers in EPA's NERL, with
substantial input from experts within and outside of the Agency. Information relevant to the
process and the document has been routinely posted on the EPA website at
www.epa.gov/nerl/sots.
NERL staff began this work by hosting a series of stakeholder meetings in the summer of
2006 to seek input on the content and format of the document. In November 2006, NERL
convened an expert panel to provide their advice and guidance about the structure and content of
this document. The expert panel consisted of 11 nationally recognized authorities in a diversity
of fields: exposure science, bioethics, epidemiology environmental health, law, community-
based research, community liaison, research in minority communities, public health, toxicology,
pediatrics, children's environmental health, etc. Details about the expert panel and the workshop
can be found in Appendix A. The summary report from the expert panel may be accessed at
http://www.epa.gov/nerl/sots/workshop-report.pdf.
The structure and content of the current report follow the recommendations of the expert
panel. Specifically, the expert panel recommended that this document should include the
following six major topic areas:
(1) elements to be considered in study conceptualization,
(2) ensuring protection of vulnerable groups,
(3) addressing privacy and other concerns related to personal exposure observational studies,
(4) creating an appropriate relationship between the participant and investigator,
(5) building and maintaining appropriate community and stakeholder relationships, and
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(6) designing and implementing strategies for effective communication.
These recommendations include pragmatic steps thatNERL scientists can undertake
during the development and implementation of observational human exposure studies. Note that
each step may require consideration and application of multiple ethical and scientific principles,
and the same ethical principle may be fundamental to several of the topic areas. As a result, the
same ethical principle may be discussed in several sections throughout this document.
Using the advice of the expert panel, an internal review draft was completed. Based on
the review comments, the internal review draft was revised, and an external review draft was
prepared. This external review draft is submitted for peer reviewed by EPA's Human Subjects
Review Board, a panel of experts chartered to review and advise the Agency on the scientific and
ethical underpinnings of research efforts. This version of the document is also intended to
undergo public comment and review. The document will be revised to respond to both the peer
review and the public comments.
1.5 Organization of the Document
The document is organized along the lines that the expert panel recommended. It has
seven sections, an Introduction followed by a section addressing each of the major topic areas.
The content of each section also is based on recommendations from the Expert Panel Workshop.
Because the authors concluded that the discussion for each topic area needed to be complete in
and of itself (i.e., capable of standing independently without having to reference other sections),
there may be some issues or topics that are discussed in several sections. Appendixes include
additional details about the steps taken to develop this document, and the List of Acronyms and
Abbreviations is followed by a Glossary, which defines important terms.
• Introduction (Section 1): Lays out the background for observational exposure research, the
scope of the document, and some of the important scientific and ethical issues that are critical
to human subjects and observational exposure research
• Study Conceptualization (Section 2): Establishes that ethical concerns are to be incorporated in
the scientific effort from the very start and includes ethical issues such as justifying the study
because of its social and scientific merit and ensuring scientific validity and independent
review
• Protection of Vulnerable Groups (Section 3): Discusses some of the special protections
afforded to vulnerable groups by EPA's human subjects rules and the ethical issues of
involving such groups in observational exposure studies
• Ensuring Privacy and Confidentiality (Section 4): Lays out the ethical issues and the
regulatory requirements, including observations of non-study hazards and the recently
discussed issues of third-party involvement or concerns
• The Participant and the Researcher (Section 5): Builds on the ethical principles of respect for
persons and beneficence to discuss the issues around recruitment, informed consent,
compensation, and the researcher's need to support the welfare of the participants
• Community and Stakeholder Relationships (Section 6): Begins with the principles of fairness,
justice, and equity and of respect for persons to develop approaches to demonstrate respect for
culture and to empower the participants' community to endure, including the need to build
trust in the community and with stakeholders through open and honest communications and
legitimate power sharing
• Strategies for Effective Communication (Section 7): Builds on the presumption of an ongoing,
interactive dialogue and exchange of ideas between researchers and the participants,
community, and stakeholders and focuses on steps that the researcher needs to take for
effective communications. The section discusses communication strategies, implementation
plans, communication tools, reporting of results, and approaches for effective
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communications, two-way communications between the researchers, participants, community,
and other stakeholders.
1.6 References
Beauchamp TL, Childress, JF (2001). Principles of Biomedical Ethics: Fifth Edition. New York, NY: Oxford
University Press.
CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection
of Human Subjects. U.S. Code of Federal Regulations. Available:
http://www.access.gpo.gOv/nara/cfr/waisidx_06/40cfr26_06.html [accessed 12 June 2007],
CIOMS (The Council for International Organizations of Medical Sciences) (2007). International Ethical Guidelines
for Epidemiological Research (Discussion Draft No. 3, April 2007). World Health Organization. Geneva.
Switzerland. Available: http://www.cioms.ch/070516april_epi_revisions.pdf [accessed 12 June 20071.
CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines
for Biomedical Research Involving Human Subjects. World Health Organization. Geneva. Switzerland. Available:
http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007],
Emanuel EJ, WendlerD, Grady, C (2000). What Makes Clinical Research Ethical? JAMA 20:2701-2711.
ERG (Eastern Research Group) (2007). Report on the Workshop to Disci&sStcfie-ofthe-Science Approaches for
Observational Exposure Measurement Studies. Final Report: January 25. 2007.
NRC (National Research Council) (2004) Research Priorities fori'Ai^borne Particulate Matter: IV. Continuing
Research Progress. Washington, DC: The National Academics Press. Available:
http://books.nap.edu/ot)enbook.php?record jd= 10957 |accessed 16 August 2007],
NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
Research. Washington, DC: The National Academics Press. Available:
http://books.nap.edu/catalog.php7record_idH0638 |acccssed 12 June 2007],
NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
Housing-Related Health Hazards Involving Children. Committee on Ethical Issues in Housing-Related Health
Hazard Research Involving Children. Youth and Families, Bernard Lo and Mary Ellen O'Connell (eds). Board on
Children, Youth, and Families. Division of Behavioral and Social Sciences and Education and Institute of Medicine.
Washington, DC: The National Academics Press. 216 pp. Available:
http://books.nap.edu/catalog.php?rccord_id=11450 [accessed 12 June 2007],
U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles
and Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of
Human Subjects of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html
[accessed 12 June 2007J.
U.S.EPA (U.S. Environmental Protection Agency) (2005). Environmental Justice Strategic Plan (Working Draft
June 16. 2005). Environmental Protection Agency. Available: http://www.epa.gov/compliance/resources/
publications/data/planning/strategicplan/ej/outline-strategicplan-publiccomment.pdf [accessed 13 June 2007],
U.S.EPA (U.S. Environmental Protection Agency) (2004). Air Quality Criteria for Particulate Matter.
Environmental Protection Agency, National Center for Environmental Assessment, Office of Research and
Development, EPA/600/P-99/002.
U.S.EPA (U.S. Environmental Protection Agency) (2002), Guidelines for Exposure Assessment. Environmental
Protection Agency, Risk Assessment Forum, EPA/600/Z-92/001.
U.S. HHS (U.S. Department of Health and Human Services) (1993). The Institutional Review Guidebook. Office for
Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm [accessed 12 June 2007],
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SECTION 2
Elements to Be Considered in Study
Conceptualization and Planning
Consideration of the scientific and ethical approaches for observational human exposure
studies begins at the very start of the study and continues throughout the study. Because such
studies involve human participants, researchers will have to consider the ethical issues associated
with the required human subjects review and approval. Consideration of ethical principles and
issues should be an integral part of all elements of the study conceptualization, scoping, and
planning, and should be included as soon as a study is proposed.
This section highlights areas that NERL exposure science researchers should consider as
they develop plans for an observational human exposui
section into context. The first stage in the research
process is to understand the state of exposure science
and EPA's programmatic needs for exposure data.
NERL scientists and managers must decide if an
observational human exposure study is necessary and
justified to meet the Agency's need. If so, then NERL
staff will enter a period of planning and scoping. A
variety of important issues will need to be considered
(identifying and enlisting stakeholders and community
representatives, forming a research team, maximizing
benefits for participants, precluding conflicts of
interest, etc.).
The planning and scoping phase will culminate
in the development of a science-based study design
and a human subjects research protocol. Although the
authors have formally separated them here for
purposes of discussion, these two items have
substantial overlap and are not fully separable. When
integrated and harmonized, moreover, they will serve as the basis for a two-pronged independent
review stage of the process. Peer review will focus on the study design and the science but also
will necessarily incorporate relevant ethical considerations. 1RB review will focus on ethics and
the protection of the human research participants but also will necessarily incorporate evaluation
of the adequacy of the study design and other relevant aspects of the science. The principle
underlying this bifurcated but integrated approach is that unsound science is unethical science.
Exposure of human subjects to any research risk whatsoever, even minimal risk, cannot be
justified if the research will not answer the scientific questions that motivated the research in the
first place.
After independent reviews evaluate both the scientific and ethical aspects of the proposed
research, EPA policy requires that the proposed study undergo internal EPA review and
evaluation by the Agency's HSRRO. Only after HSRRO approval can any research actually
begin. As the NERL study is implemented, project data and concerns of the participants will be
monitored on a continuing basis and compared with previously established standards and criteria
to evaluate whether the study is on target for meeting its objectives, or if some unforeseen
re study. Figure 2-1 puts the text in this
Problem
Conceptualization
Define & Justify
the Study
Planning
&
Scoping
Develop Study
Develop Human
Design
Subjects Protocol
Independent
Review
Peer Review
IRB Review
Scientific & Ethical
Ettiical & Scientific
Review
Review
Agency
HSRRO
Review
HSRRO PaappmvB
' Review Ho Study
\ /
Approve ¦ Conduct Study
Criteria I OK
Implement
Study
&
Monitor Contmue Stixfy
Progress
Implement ' - f
& Monitor
Criteria Exceeded
Terminate Study
Figure 2-1: Stages in the Development of a NERL
Observational Human Exposure Study
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circumstances indicate that the study should be stopped immediately on either scientific or
ethical grounds.
2.1 Problem Conceptualization
Problem conceptualization involves understanding the state of exposure science and
EPA's programmatic needs for exposure data. NERL scientists and managers must decide if an
observational human exposure study is necessary and justified to meet the Agency's need.
2.1.1 Defining the Study Problem
Observational studies historically have been performed for many different purposes and
in many different fields of research - social behavioral, economic, biological, medical,
epidemiological, and exposure science. NERL has used observational human exposure studies to
understand how people come into contact with pollutants in their everyday lives, with the
ultimate goal of protecting public health. NERL's exposure research program addresses critical
science needs directly related to Agency goals for protection of human health. The research
program is driven by key exposure science questions that may be generated from a number of
different sources, including legislative mandates (e.g., the Food Quality Protection Act, the
Clean Air Act, the Safe Drinking Water Act), program offices or research planning groups in the
Agency, scientific peers and researchers, or collaborators. Communities also may identify
concerns about exposures in their locales. NERL's observational human exposure studies collect
data to improve exposure and risk assessments, to develop risk management strategies, and to
substantiate informational and educational materials for use by EPA program offices (e.g., Office
of Pollution Prevention and Toxic Substances, Office of Air and Radiation, Office of Children's
Health Protection).
Emanuel et al. (2000) argue that an ethical research study must provide a worthwhile
social or scientific value. For observational human exposure studies, this means that the study
should provide both a scientific value and a social value to the participants and their community.
Researchers should work with communities to develop studies that can help address community
problems and maximize the benefit to the participants and the community, both of which also
assume a burden for participation in a research study.
2.1.2 Justifying the Study
Justification of any human study includes
both a scientific and an ethical justification.
Emanuel et al. (2000) list seven ethical
requirements that must be met for human subjects
research to be considered ethically acceptable.
Four of those requirements—(1) respect for
subjects, (2) informed consent, (3) favorable
risk/benefit ratio, and (4) fair subject
selection—are founded on the traditional ethical
principles enunciated in the Belmont Report and
codified in the Common Rule. But three
requirements—(1) social or scientific value, (2)
scientific validity, and (3) independent
review—also touch on other related scientific
aspects of the study. Similarly, Guideline 1 from
the CIOMS (2002) document reiterates the
foundational principle that "scientifically invalid
research is unethical." Beyond the traditional ethical expectations of respect for, protection of,
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Text Box 2-1. Elements to be Considered in
Justifying a Study
The research problem and questions to be ad-
dressed in the study,
The objectives of the study and/or the hypotheses to
be tested,
A discussion of why human participants are required
for the study,
Available information on the need for the study (i.e.,
it is not redundant and the research question has
not already been answered),
Available information from the scientific literature
demonstrating the relevance of the proposed study,
A discussion of the general technical approach and
scientific soundness of the approach,
An assessment of the needed competencies and
qualifications of all personnel involved in conducting
the research,
The likelihood of success in meeting the study goals
and objectives (including an evaluation of the accu-
racy, precision, and quality assurance of the data
needed to attain the study goals and objectives),
and
Justification for the investment of time and money.
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and fairness to the research subjects, CIOMS requires investigators and sponsors to ensure that
the research be "scientifically sound," that it "conform to generally accepted, scientific
principles," and that all researchers be "qualified" and "competent."8 Text Box 2-1 identifies a
number of elements that should be considers in justifying an observational human exposure
study.
2.2 Planning and Scoping
Once the study problem has been defined and justified, the first step in planning and
scoping the study is to form the research team. The team should be diverse, including the
technical experts (researchers), stakeholders, and representatives and members of the community
in which the study will be performed. For scientific, ethical, and practical reasons, the
community should be appropriately involved throughout the study, including the scoping and
planning phases. Information on identifying and engaging community members in the process is
described in Section 6 of this document.
Translating the information developed in defining the problem and justifying the study
into a real, workable, feasible study design and human subject protocol is an iterative process
involving input from all of the members of the research team. Scientific and technical expertise
is required to assure the scientific integrity of the research, including developing the conceptual
model9 for the effort and devising a reliable sampling and analysis plan. Stakeholder input is
critical to assuring that the generalizable research information from the study will actually be
applicable for addressing the study problem. Community input is particularly important during
the planning and scoping stage because the community representatives can provide valuable
information about the community members (the future study cohort), the cultures of the
community, community values, community concerns, feasibility of working in the community,
information needed to develop the technical approach, and information on important factors like
pollutant sources and other stressors in the community. (Additional considerations for
communicating and working with both the participants and the community in which they live are
the topics of Sections 5 through 7 of this document.)
In developing the study design and the human subjects protocol, the research team often
will have to deal with a variety of complex issues, including how to maximize benefits for
participants, the community, and the stakeholders, and how to ensure the integrity,
generalizability, and representativeness of the study. Recent events, including court cases and
8 Guideline 1 stales "research can be ethically justifiable only if it is carried out in ways that respect and protect, and
are fair to, the subjects of that research and are morally acceptable within the communities in which the research is
carried out. Moreover, because scientifically invalid research is unethical in that it exposes research subjects to risks
without possible benefit, investigators and sponsors must ensure that proposed studies involving human subjects
conform to generally accepted scientific principles and are based on adequate knowledge of the pertinent scientific
literature." The commentary on the Guideline goes on to say, "Among the essential features of ethically justified
research involving human subjects, including research with identifiable human tissue or data, are that the research
offers a means of developing information not otherwise obtainable, that the design of the research is scientifically
sound, and that the investigators and other research personnel are competent. The methods to be used should be ap-
propriate to the objectives of the research and the field of study. Investigators and sponsors must also ensure that all
who participate in the conduct of the research are qualified by virtue of their education and experience to perform
competently in their roles. These considerations should be adequately reflected in the research protocol submitted
for review and clearance to scientific and ethical review committees."
9 A conceptual framework or model is often an effective approach to describe the relationship between the predicted
exposures of the population and the population stressors, laying out the predicted pathways and routes of exposure
(e.g.., see Cohen Hubal et al., 2000). A conceptual model often is illustrated by a block diagram that represents the
major scientific processes and interactions. The model is often very useful in developing an analysis plan that de-
scribes the hypotheses or objectives of the study, identifies the data needed to address the objectives, and specifies
the analyses that will be done to test the hypotheses or address the objectives.
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human subjects study controversies, have highlighted four issues, in particular, that the authors
suggest should be thoroughly addressed early in the planning and scoping phase of the study.
Those four topic areas—innovative study designs that maximize benefit to the participants,
careful assessment of the risks and benefits of the study, ensuring that the study does not coerce
risky behavior, and avoiding actual or perceived conflicts of interest—are discussed in the
following sections.
2.2.1 Innovative Study Designs
Study designs vary depending on the objectives of the study, existing knowledge on the
research question, and the hazard being studied (NRC & IOM, 2005). Recent ethical discussions
about study designs in human subjects research (cf., Recommendation 7.1, p. 143, NRC & IOM,
2005) and Emanuel et al (2000)) support the development of innovative study designs to
maximize the benefit10 to the study participants, as well as to the community and the greater
society beyond. Observational human exposure studies generally collect data that contribute to
generalizable knowledge that will benefit the community and the society as a whole, but they
often do not provide obvious direct benefit to study participants. Therefore, it is important to
include elements in the study design that can offer benefits to the participants wherever possible.
This is not always straightforward, but one way that participants, as well as communities, can
benefit from observational studies is by incorporating strong educational components into the
conduct of the research. For example, brochures, videos, and other materials that educate study
participants on safety around the home or on how to reduce their exposure to chemicals can be
distributed during the study. EPA's program offices, including the Office of Children's Health
Protection, the Office of Pollution Prevention and Toxics, the Office of Pesticide Programs, the
Office of Drinking Water, and others have Web sites with substantial amounts of informational
material and hardcopy brochures and educational materials available that could be distributed to
study participants. Other organizations, such as the American Lung Association, the American
Cancer Society, the American Academy of Pediatrics, and various environmental groups, have
materials that study participants may not be aware of that could be used as educational materials
when relevant.
In addition, approaches that provide direct benefits to study participants will need to be
tailored to the particular study population and community. Feedback from potential participants
in focus groups and input from community representatives may be useful in identifying these
approaches.
2.2.2 Assessing Benefits and Risks of Study Participation
For all research involving human participants, the Common Rule requires researchers to
ensure that potential risks "are reasonable in relation to the anticipated benefits," and that risks
are minimized (40 CFR 26.111). It is most useful if the assessment of benefits and risks is begun
early in the scoping and planning phase of a study.
Unlike some biomedical research that involves the study of interventions or procedures
that hold out the prospect of direct diagnostic, therapeutic, or preventative benefit for the study
participants, observational human exposure measurement studies often do not have a similar
prospect of direct benefit to the participant. Therefore, the risk/benefit balance is based on the
balance between the risks to the participants and the expected benefits to society (generalizable
knowledge). The risks presented in observational studies have to be reasonable [40 CFR
26.111(a)(2)] in relation to the importance of the knowledge gained. This assessment of the
10 Compensation to participants is never considered a benefit of a study.
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risk/benefit balance, therefore, needs to be performed in the initial scoping and planning of the
study to be included in the justification for the study (Section 2.2).
If there is no prospect of direct participant benefit, and the study participants are children,
moreover, EPA is permitted to conduct or support only those observational exposure studies that
meet the regulatory definition of "minimal risk" found in the Common Rule at 40 CFR 26.102(i)
and reiterated in Subpart D of the EPA Rule at 40 CFR 26.402(g): "Minimal risk means that the
probability and magnitude of harm or discomfort anticipated in the research are not greater in
and of themselves than those ordinarily encountered in daily life or during the performance of
routine physical or psychological examinations or tests." In applying this definition, EPA
adheres to the consensus standard that the reference population for this definition is normal
children living in safe, healthy environments. In its discussion of the perception of risks and
benefits, the NRC & IOM (2005) report on housing health hazards in children notes that the
children participating in these studies may be at risk for physical harms or adverse health
outcomes because they live in housing (or occupy other environments) with health hazards.
However, such risks are not introduced by the research but rather would be present whether or
not the children were involved in a research study. As a consequence, the study would still meet
the regulatory criteria for minimal risk as long as the research /V.st'//'introduced no risks over and
above those minimal risks experienced by normal children living in safe healthy environments.
However, the existence of greater-than-minimal background risks that are not introduced
by the research nonetheless raises additional ethical considerations. The joint NRC & IOM
Committee on research on housing-related health hazards involving children discussed the
ethical arguments that arise when scientists conduct research that observes children in poor-
quality housing. They point out that a researcher's first duty of beneficence under the Common
Rule requires that the risks of the research actions be proportionate to ["reasonable in relation
to", 40 CFR 26.111(a)(2)] the benefits of the research and that the risks be minimized. They
acknowledge, however, that some have argued that the "best interests of the child" also obligates
researchers to "rescue" children from harm and to provide better living conditions. They
conclude that, properly applied, the ethical principle of beneficence does indeed direct
researchers who observe serious harms to child subjects to take steps to try to prevent the harms.
However, they also argue that the researcher's duty does not extend to "personally and directly
prevent harm by removing the child from the harmful environment" (p. 60, NRC & IOM, 2005).
They conclude instead that "it is unrealistic and unfair to hold individual research investigators
responsible for ameliorating the social circumstances that they study" and that "a nuanced
balancing of the benefits and risks of research" is an ethically sound approach that is firmly
established in Federal regulations (p. 60, NRC & IOM, 2005). Balancing the ethical obligation to
mitigate risks and/or harms observed during research with the reasonable limits on an
investigator's moral responsibility for the social circumstances surrounding the research will be
the subject of later sections of this document, particularly Section 4.3.1.
Assessing the risks and benefits of the research study can be very difficult for the
researchers, especially since the researchers and the community or participants may perceive the
risks and benefits quite differently. [See the discussion in NRC & IOM (2005), for example.] To
understand the community's perspective better researcher may find it helpful to discuss the
assessment of risks and benefits with members of the research team, community representatives,
and relevant stakeholders. The research team should consider the use of a Community advisory
board (CAB) to provide input to the assessment of the risks and benefits of the study. The group
could include individuals who are representative of the population to be studied, community
representatives, exposure scientists, and bioethicists. The group should include experts familiar
with the human subjects research regulations, preferably including someone who has served on
IRBs. Obtaining input from the group can be accomplished by submitting the study concept and
general study design to the group for review and feedback, even before a full study design has
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been developed. (See the discussions of CABs in Sections 5 and 6.) Ultimately, it will be the
review by the members of the IRB that will determine whether the balance is appropriate and
justifiable.
2.2.3 Ensuring That Participant Behaviors Are Not Adversely Changed Because of
Being in the Study
The goal of observational human exposure studies is to collect information on people's
exposures to chemicals in their real-world environment as they carry on their normal daily
activities. Researchers who conduct observational studies, however, recognize that participation
in a study may affect people's behavior. This cannot always be avoided, as the simple fact that a
person agrees to participate in a study may impact the participant's activities and schedules. For
example, this occurs when technicians visit homes to collect samples or when participants are
asked to collect samples (e.g., food, urine), or to complete surveys, activity logs, or
questionnaires. These types of changes in behavior may or may not affect the outcome of the
study.
Some changes in behavior during an observational study can affect the study outcome.
The Hawthorne Effect is a well-recognized phenomenon in group-based observational research.
It is an effect on an outcome variable caused by the fact that the participants of the study know
they are participating in the study. The Hawthorne Effect originally referred to the increase in
worker productivity observed when a worker is singled out and made to feel important; the
increased productivity was not related to the environmental factors that were being studied. The
effect was described based on a series of industrial productivity studies from 1927 to 1932.
Similarly, some changes in participant behaviors may change the observations, measurements,
and conclusions from observational studies. For example, participants may do more cleaning in
their home because they do not want the researchers to think they are poor housekeepers: this
could affect the measurement of environmental concentrations in the home. In a study of
chemicals from consumer products, participants may think that because the researchers are
studying the products, they have to be "bad." Therefore, study participants may elect not to use
the products during the study in the same manner as they would normally. Alternatively,
potential participants may choose to use more of the household product to qualify to participate
in the study. As a result, the participant's exposure to the chemicals could be either more or less
than "normal."
Any change in a participant's behavior that is
related to the research question being addressed in the
study may impact the study results. Researchers should try
to anticipate how a study may impact participant behaviors
and ensure that the study design and implementation
protocols do not cause changes in behavior that may cause
harm to a participant during a study. A number of study
elements with the potential to influence participants'
behavior are listed in Text Box 2-2.
It is very difficult to predict in advance how these
elements may be interpreted and acted on by the
participants. Researchers may learn from the experiences of others, including the "lessons
learned" from experts and their publications. They may wish to engage the community
representatives (see Section 6) in a thorough discussion of the issue. Community-based focus
groups or pilot studies also may demonstrate how the various elements of the study may have an
unintended impact. Additionally, researchers can be very careful in the informed consent process
(see Section 5.1), to ensure that participants not only know, but that they understand the facts of
Text Box 2-2. Study elements that
could affect people's behavior
Eligibility criteria,
Recruiting approach and materials,
Enrollment approach,
Compensation package,
Retention strategy,
Types of measurements made and data
collected,
Protocols for data collection,
Protocols for visits to homes,
Interactions with the participants, and
Communications.
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the study (Gilbert, 2006), and that they comprehend that the goal is to observe and measure the
participant's exposures during their normal, everyday activities.
2.2.4 Conflicts of Interest (Including Funding)
It is recommended that potential conflicts of interest among researchers or study
participants be identified at all stages of study planning and implementation, but particularly
early in the study during the planning and scoping stage. There can be many sources of conflicts
of interest, but those related to project funding are the most likely to occur. Other types of
conflict of interest may arise from consulting arrangements of the investigators, employment of
investigators' family members with affected parties, participation in affected advocacy groups,
collaborations or relationships with experts on the IRB or other independent review committees,
institutional conflicts for any contractors who may be involved, or a wide range of other
situations.
It is highly recommended that researchers disclose all potential or apparent conflicts of
interest on their part to the IRB. The CIOMS (2002) guidelines for research protocols involving
human subjects specify that all sponsors of the research be identified, and that the protocol
include actions to disclose and address potential conflicts of interest. Concerns about conflicts of
interest also need to be identified and discussed with the researchers, community, and other
stakeholders to make a determination of the existence of conflicts, and how they should be
avoided or handled.
Even if actual conflicts of interest do
not exist, researchers should recognize that
there can be perceived conflicts of interest that
can be just as damaging as real conflicts of
interest. Perceptions by participants,
community members and representatives,
stakeholder groups, and the public may be
substantially different from the reality of the
situation. This is especially likely to occur
when external sources, such as industry, are
involved in funding research. Even though
researchers may develop agreements with
funding organizations that ensure researcher
autonomy, a perception may exist that the
funding organization will bias the study
(Resnik and Wing, 2007). Concerns about
perceived conflicts of interest should be
discussed with the IRB and other relevant
review committees, in addition to the
researchers, the community, and other
stakeholders.
2.3 Study Design
To facilitate scientific and ethical
review, the research team members should
develop a comprehensive and detailed study
design that describes the technical approach for
the observational study. Although the format
and scope may vary depending on the specific
study, there are a number of basic elements
Text Box 2-3. Elements That May Be Included in a
Study Design
• Introduction and Background, including the purpose and
scope of the study
• The desired outputs and outcomes of the study, including
the objectives and the hypotheses to be tested
• A brief description/overview of the study
• The technical approach and conceptual model that
accounts for
o sources of the chemicals being studied;
o potential routes and pathways of exposure;
o factors that may impact exposure, and other relevant
stressors;
o selection and characteristics of the study participants;
eligibility criteria; and recruitment, retention, and
compensation approaches;
o characteristics of the community in which the study will
be performed;
o environmental conditions, factors, or end points to be
measured, including sampling and analysis
approaches;
o survey design and questionnaires and other survey
instruments, as applicable;
o pilot studies that may be undertaken;
o quality assurance project plan and quality control;
o time frame for the study;
o exposure scenarios to be considered;
o burden of the study on the participants;
o resources available; and
o feasibility
• An analysis plan that considers
o information/data needs, including data storage,
security, access, and release;
o nature of the measurement data (e.g., variability, quality
assurance); and
o hypotheses to be tested and statistical power and
sample size required to test the hypotheses
• Resources required or available
• Project organization and management, including team
members and roles and responsibilities
Schedule
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generally included in the study design.
The study design should contain sufficient detail to allow independent review and
assessment of the scientific soundness of the study and the approaches that will be followed to
ensure that the study meets the highest scientific and ethical standards. The research team can
meet regularly to specifically evaluate the plan. It should be noted that a study design is not the
same as an implementation plan. The latter includes an even greater level of detail describing
how the study will be performed and includes protocols and operating procedures. Text Box 2-3
lists a number of elements that may be appropriate to include in a study design.
2.3.1 Feasibility
The authors consider the evaluation
of the feasibility of accomplishing the
study to be one of the most critical
components of the development of the
study design. If the research team
concludes that the study is not feasible,
there will be no further effort to develop
the study. There may be practical
limitations that preclude conduct of the
study as initially conceived. Evaluation of
the feasibility of a study involves both
scientific and ethical considerations.
Because "scientifically invalid research is
unethical" (Guideline 1, CIOMS, 2002), it
is essential that scientific and ethical
considerations be considered together. Text
Box 2-4 includes some examples of the types
feasibility of a study.
2.3.1.1 Sample Size Determination
One critical issue in assuring that an observational human exposure study is scientifically
valid (and thereby not invalid and unethical) is the issue of sample size. EPA's Science Advisory
Board has stated, "Bad science is always unethical; research protocols that are fundamentally
flawed, such as those with sample sizes inadequate to support reasonable inferences about the
matter in question, are unjustifiable." [p. 2, item (c), U.S. EPA, 2000]
A study has to have an adequate size to meet the study objectives. If the sample size is
too small, the results may not be statistically significant, and the results may not be either valid
or generalizable. Such a result would be a waste of resources or cause undue burden on study
participants without generating the intended generalizable knowledge that will benefit society.
On the other hand, if the study sample size is larger than necessary to meet a study objective, this
also may result in a waste of resources or the imposition of needless burden on participants.
Sample size determination is an important step in planning a study, but it can be a
difficult task (Lenth, 2001). Dr. Russell Lenth, a faculty member of the Department of Statistics
at the University of Iowa, is often cited for his work on sample size determination, including a
Web site where he provides applets for power and sample size calculations
(www.stat.uiowa.edu/~Rlenth/Power/index.html). Lenth notes that there is a surprisingly small
amount of literature on sample size determination, and he provides some suggestions on
approaches to address the issue. .
It is critical that sample size be determined at the time of study conceptualization and
planning and not after the study already has been conducted. Researchers should refer to the
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Text Box 2-4. Is the Study Feasible?
What are the sample size requirements? Carr^rSftigff partici-
pants be enrolled into the study from the proposed community,
considering the eligibility criteria and anticipated response
rate? What is the predicted retention rate if this is a repeated
measurements study? Is that acceptable?
Will the community be receptive to this study?
Are there cultural mores, societal values, or other factors as-
sociated with the community that would make it difficult to
conduct the study in the community? Is the study morally ac-
ceptable to the community?
Is there a community; structure that will allow the research
team to engage the community in the study?
What is the burden on the community?
What is the burden on the participants? Is it acceptable?
What is thejjsk/benefit balance? Is it acceptable, considering
the burden on the participants?
Are there sufficient resources available to conduct a study of
this size?
Are resources available for community outreach and sustained
interactions with the community? Are resources available to
^support community members involved in the study?
of questions that may be asked when evaluating the
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Lenth (2001) article, biostatistics books, and other references (Castelloe, 2000; Kraemer and
Thiemann, 1987; Van Belle et al., 2004; Wackerly et al., 2001) for more information on this
topic.
2.3.1.2 Quality Assurance Project Plan.
Data of unknown or uncertain quality can undermine the scientific integrity of a study
and render an otherwise sound study invalid. NERL scientists must be diligent in the
implementation of the procedures and processes specified in a well-developed quality assurance
project plan (QAPP). A discussion of quality assurance programs and QAPPs is outside of the
scope of this document. There are many good references on the topic, including the EPA Web
site, www, epa. gov/qualitv/.
2.4 Human Subjects Protocol
Institutional Review Boards may
have specific format requirements for their
human subject research protocols.
Traditionally, the human subjects research
protocols for research conducted or funded
by NERL has included descriptions of the
project, including title and description of the
research; the duration of the project; the type
of data to be collected; the objectives of the
study; the number of samples; a description
of the participants and participant
recruitment procedures; the informed
consent procedures and forms; estimates of
participant risk and burden, an assessment of
benefits and the risk/benefit ratio; and
actions to protect the participants. CIOMS
has developed a comprehensive list of items
that they recommend for inclusion in a
human subjects research protocol (Appendix
1, CIOMS, 2002). Many of the items that
they identify are also useful for
observational human exposure studies. (The
CIOMS items can be found in Appendix B
of this document.) The authors recommend
that anyone developing a human subjects
protocol for observational human exposure
studies review and utilize the CIOMS list of
topics, as appropriate. Text Box 2-5
identifies a number of topics that should be
considered in development of the human
subjects research protocol.
In addition, the authors' experience
leads them to suggest that three additional
topics beyond those from the CIOMS (2002)
document also may need to be considered in
a human subject protocol: (1) approaches to
minimize changes in participant behavior
Text Box 2-5. Potential Topics in a
Human Subjects Research Protocol
1. Title
2. Summary in lay language g %.
3. Justification for the study
4. Ethical issues and proposed resolution
5. Summary of previous research
6. Affirmation of Belmont Report and 40 CFR 26 compliance
7. Previous history or use:7of the protocol
I 8. Information on the location/demographics of research
9. Information on funding organization, researcher partners,
and collaborators
I 10. Names, qualifications, and experience of investigators
'11. Objectives, hypotheses, assumptions, and variables
12. Study design
13. Sample size and statistical analysis/power
14. Criteria and justification for subject selection
15. Justification for use of vulnerable groups, if any
16. Process of recruitment
17. Actions to involve the community in a community-based
participatory research program
18. Description and explanation of any and all interventions
19. Measurements or data to be collected
20. Any clinical and other tests
21. Rules or criteria for removing subjects or terminating the
study
22. Adverse events—reporting and responses
23. Potential benefits to subjects and to others
24. Expected benefits of the research to the population
25. Informed consent process and responsibilities
26. Protections for the consent/assent of vulnerable participants
27. Efforts to minimize "therapeutic misconception"
28. Approaches to minimize changes in participant behavior
29. Compensation or incentives
30. Plans for informing subjects about items that could affect
subjects' willingness to continue in the study
31. Plans to inform subjects about the results of the study
| 32. Privacy and confidentiality
33. Security of personal information and when, how, and by
whom private information can be revealed
I 34. All foreseen uses of personal data or biological materials
35. Procedures for monitoring and oversight of the study and
criteria for reporting and responding to adverse events,
including prematurely terminating the study if necessary
36. A list of the references cited in the protocol
if 37. The source and amount of funding
38. Protocols for dealing with financial or other conflicts of
I interest
39. Schedule
40. Arrangements with sponsors regarding publication
rights/procedures
41. Circumstances for not publishing the study findings
42. Procedures for dealing with falsification of data
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because of participation in the study (see Section 2.3.4 above), (2) approaches to minimize
therapeutic misconception (see Section 5.4.1), and (3) actions to involve the community in a
community-based participatory research effort, as appropriate (see Section 6, especially Section
6.10).
2.5 Independent Scientific and Ethical Review
Because issues of science and ethics are intrinsically bound together in human subjects
research (Emanuel et al., 2000: CIOMS, 2002), it is important that scientific and ethical reviews
be considered together, not separately. Scientific reviews are performed to ensure the scientific
soundness of the study, whereas ethical reviews are performed to ensure proper action and the
protection of the human subjects in a research study. A study that is not scientifically sound
could expose study participants to unnecessary risk or inconvenience and burden, with no
additional societal benefits (i.e., no increase in generalizable knowledge). EPA's Science
Advisory Board has stated that "bad science is always unethical" (U.S. EPA, 2000), and CIOMS
declares that "scientifically invalid research is unethical" (CIOMS, 2002)11. It is clear, therefore,
that the ethical review has to consider the scientific aspects of the study also.
There may be multiple levels of review during development of the study design and
human subjects research protocol for an observational human exposure study. The research team
is responsible for the design of the study and for ensuring that adequate peer review is performed
to evaluate both the scientific and ethical approaches for the study. Following completion of a
draft study design, researchers should engage a diverse group of experts to review the study
design and human subjects aspects. The scope of the study should dictate the level of the review
(i.e., internal independent peer review versus external peer review versus both). A small pilot
study to evaluate measurement methods or to collect screening level data in preparation for a
large study may not require as extensive review as a larger study.
When the scientific soundness of the study has been evaluated and found to be feasible,
and the final study design is completed, the human subjects research protocol should be
developed and submitted to the 1RB for review and approval. For studies conducted or supported
by EPA, additional review and certification of the human subjects research protocol is required
by EPA Order 1000.17 Al. (www.epa.izov/oamrtpnc/forms/1000 17a.pdf). Review and approval
of the protocol and associated documents must be obtained from EPA's HSRRO, located in the
EPA Office of the Science Advisor, before any work begins.
2.5.1 Scientific Peer Review
For all studies, regardless of the scope, the research team should solicit review and
comment on the scientific approach by experts external to the research team. A peer review panel
consisting of individuals who were not involved in the design of the study can be formed to
review the scientific soundness of the study. It is important for the panel to consist of individuals
11 CIOMS (2002) Guideline 2 asserts "Ethical review committees—All proposals to conduct research involving
human subjects must be submitted for review of their scientific merit and ethical acceptability to one or more scien-
tific review and ethical review committees. The review committees must be independent of the research team, and
any direct financial or other material benefit they may derive from the research should not be contingent on the out-
come of their review. The investigator must obtain their approval or clearance before undertaking the research. The
ethical review committee should conduct further reviews as necessary in the course of the research, including moni-
toring of the progress of the study." The CIOMS document continues "According to the Declaration of Helsinki
(Paragraph 11), medical research involving humans must conform to generally accepted scientific principles, and be
based on a thorough knowledge of the scientific literature, other relevant sources of information, and adequate labo-
ratory and, where indicated, animal experimentation. Scientific review must consider, inter alia, the study design,
including the provisions for avoiding or minimizing risk and for monitoring safety. Committees competent to review
and approve scientific aspects of research proposals must be multidisciplinary."
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with experience and background appropriate to the study and to include members with
knowledge of the ethical principles for protection of human subjects in these types of studies.
The panel would also benefit from including someone with sufficient background and expertise
in statistics to evaluate whether the study design, sample size, and proposed data analyses are
appropriate and adequate to address the study objectives or test the hypotheses. For small studies,
the peer review panel may consist of individuals within the organization conducting the study if
they have not been involved in developing the study design. For larger and complex studies, it is
recommended that an external peer review panel be convened to review both the scientific and
ethical soundness of the study design.
For research conducted or sponsored by NERL, human subjects research efforts will
undergo both a scientific review and an ethical review. The director of the division conducting or
funding the observational research is the manager with the primary responsibility for ensuring
that the scientific and the ethical reviews are conducted, and that the review comments are
properly addressed. The study design will be reviewed for scientific quality by independent and
knowledgeable reviewers. Depending on the scope of the study, the appropriate NERL associate
director or the NERL laboratory director will make the final determination about (1) the process
for selecting scientific peer reviewers (including the range of disciplines to be included), (2) the
nature and scope of the review process (e.g., charge to the reviewers and scope of the review;
letter reviews, convening a peer panel, or both; the size and nature of the panel review; etc.), and
(3) the adequacy of the responses to the scientific review.
2.5.2 Ethical Review
In the United States, ethical reviews of studies involving human subjects are performed
by IRBs. The Common Rule specifies requirements (40 CFR 26.107 - 115) for IRB
membership, IRB functions and operations, IRB review of research, and other details related to
IRB review and approval of research. Emanuel states that "the independent ethical review of
[human subjects research] should involve individuals with training in science, statistics, ethics,
and law, as well as reflective citizens who understand social values, priorities, and the
vulnerability and concerns of potential subjects" (Emanuel et al., 2000). It is beyond the scope of
this document to include detailed discussions on IRB membership, operations, processes, etc.
The reader is referred to the Common Rule, as well as a number of other available references
(e.g., OHRP, 2007; CFR, 2006; HHS, 1993; NRC, 2003).
It is essential that research with human subjects be carried out or strictly supervised by
suitably trained, qualified, and experienced investigators. For all research subject to the Common
Rule, these qualified researchers are expected to prepare a human subjects research protocol (as
in Section 2.5) and to submit the protocol to be ethically and scientifically appraised by one or
more suitably constituted IRBs, independent of the investigators.
There are a number of other issues associated with IRBs that may impact researchers
conducting observational studies. As an example, there has been concern about the transparency
of IRBs. Questions have been raised about what information the IRB should make available to
the public regarding membership on the IRB for review of individual projects, the discussions
held with the researchers, their concerns about the research protocol, the researchers' response,
etc. Should this information be documented in files that the researchers can make available to the
participants, community, stakeholders, and the public? At the present time, there is no clear
approach on how to address these issues. Because these issues are associated with the IRB, not
the researcher, it is outside the scope of this document to recommend approaches for IRBs to
address these concerns. IRB processes and procedures will continue to evolve, as recommended
by various committees and workgroups (e.g., as reported in NRC & IOM, 2005; NRC, 2003:
HHS, 1993).
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All human subjects research conducted or sponsored by NERL is subject to both the 40
CFR 26 requirements and the procedures set forth in EPA Order 1000.17 Change A1
(www.epa.gov/oamrtpnc/forms/1000 17a.pdf). The EPA order establishes as policy that all
research shall comply with the Common Rule and with the order. All human research studies
must be reviewed and approved by the EPA HSRRO before the work can start.
In NERL, the director of the division conducting or funding the observational research is
the manager with the primary responsibility for developing the human subjects research protocol
and for having that protocol reviewed by an independent IRB acceptable to the EPA HSRRO.
The protocol also shall be reviewed by the NERL HSRRO and by the appropriate NERL
associate director before it is submitted to the IRB. Under 40 CFR 26.109, the IRB can demand
changes to the research protocol and is the final authority for approving or disapproving the
research activity.
2.6 Internal EPA Review of Scientific and Ethical Issues
After IRB approval is obtained, the division director will be the primary manager
responsible for preparing a request for review and approval or exemption of the human subjects
research by the EPA HSRRO. The division director will work with the NERL HSRRO and with
the appropriate NERL associate director to prepare the package, consistent with EPA Order
1000.17 A1 and all other policies or procedures that the EPA HSRRO may have established. The
EPA HSRRO shall be the final authority for approving or disapproving the research effort. The
EPA HSRRO may request additional reviews or establish additional policies and procedures for
seeking review and approval. No human subjects research will begin—not even recruiting of
potential participants—until the EPA HSRRO has approved or exempted the research.
2.7 Establishing Criteria and Standards for Monitoring Scientific and Ethical Issues
During a Study
CIOMS recommends that all human subjects research protocols contain "A description of
the plans for statistical analysis of the study, including plans for interim analyses, if any, and
criteria for prematurely terminating the study as a whole if necessary" (Item 38, Appendix A,
CIOMS, 2002). To be consistent with this recommendation, the research team will need to
develop and implement an approach for monitoring the scientific and ethical issues during the
study so that changes can be made to the study or the study can be stopped if necessary. Criteria
and standards need to be established
against which study activities and results
can be evaluated, and these criteria and
standards need to be incorporated into the
study design, the human subjects research
protocol, and the QAPP.
In developing an approach to
monitor scientific and ethical issues during
the study, the research team may choose to
• identify the individual, team, advisory
committee, or data safety monitoring
board responsible for monitoring the
progress and results of the study;
• develop roles and responsibilities;
• develop a schedule and timeline for the
activities to be conducted;
• develop goals for interim data analysis
and prepare an analysis plan;
Text Box 2-6. Examples of Issues That May Cause a
Study To Be Stopped Early
• Participant recruiting and enrollment—low response rates,
disproportionate enrollment of select groups, problems
associated with advertising, inadequate selection criteria
• Informed consent—difficulties with the process and materials,
poor comprehension
• Participation—poor response to questionnaires, poor compliance
with researcher requests on data collection activities
• Burden—higher than predicted burden
• Changes in participant behaviors - potential changes because of
participation in the study
• Grievances—participant issues
• Retention—high dropout rates
• Community issues—poor interactions, lack of support
• Third-party issues—problems with landlords, spouses, and
others
• Collateral observations—identification of nonstudy hazards,
difficulty reporting
• Unanticipated results—high contaminant concentrations
measured, unexpected results
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• identify what data will be analyzed, how it will be processed and validated, and who will
perform the analyses;
• develop a plan for reporting interim results to the research team;
• develop standards for reporting scientific and ethical issues to the research team; or
• develop criteria for evaluating scientific and ethical issues that arise during the study.
In a well-designed observational study for which the research team has adequately
prepared, it is unlikely that there will be scientific issues requiring that the study be stopped.
Nonetheless, it is important for criteria to be established for when the study needs to be changed
or terminated. An example might be the participant retention rate. In a study with repeated
measurements, a certain sample size is required to obtain statistically significant results. If the
retention rate is poor, and too many participants drop out of the study, it may not be possible to
meet the study objectives, and early termination of the study may be warranted. However, it is
anticipated that the study design would include contingency planning (for example, related to
replacement).
However, developing criteria for study elements that may have associated ethical
concerns as a study progresses will be much more difficult. There are no standard formulas for
dealing with ethical concerns. For example, if the privacy of a number of study participants is
compromised by a technician conducting the measurements in their homes, what criteria should
be used to evaluate the severity of the issues? How many landlord-participant problems are too
many before the study needs to be changed to exclude participants who rent their dwellings?
2.8 References
Castelloe J (2000). Sample size computations and power anal> sis with the SAS System. Paper 265-25 in
Proceedings of the 25th Annual SAS Users' Group International Conference, Cary, NC: SAS Institute, Inc.
CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection
of Human Subjects. U.S. Code of Federal Regulations. Available:
http://www.access.gpo.gov/nara/cfr/waisid.\_06/40cfr26_06.html [accessed 12 June 2007],
CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines
for Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
http://www.cioms.ch/framc_guidclines_nov_2002.htm [accessed 12 June 2007],
Cohen Hubal EA, Sheldon LS. Zufall MJ, Burke JM, Thomas K (2000). The challenge of assessing children's
residential exposure to pesticides../ Expo Anal Environ Epidemiol 10:638-649.
Emanuel EJ, Wcndlcr D. Grady C (2000). What Makes Clinical Research Ethical? JAMA 20:2701-2711.
Gilbert SG (2006). Supplementing the traditional institutional review board with an environmental health and
communiU review board. Environ Health Perspect 114(10): 1626-9.
Kraemcr HC. Thiemann S (1987). How Many Subjects? Statistical Power Analysis in Research. Newbury Park, CA:
Sage Publications.
Lenth RV (2001). Some practical guidelines for effective sample size determination. American Statistician 55(3):
187-193. Available: http://www.stat.uiowa.edu/techrep/tr303.pdf [accessed 13 June 2007],
Menikoff J (2005). Human Subject Testing of Babies, Bugs, and Bombast: A Look Behind the Crash-and-Burn of
the CHEERS Pesticide Study. Medical Research & Law Policy Report 4(14):586-512.
OHRP (Office for Human Research Protections) (2007). U.S. Department of Health and Human Services [Online].
Available: http://www.hhs.gov/ohrp/ [accessed 13 June 2007],
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NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
Research. Panel on Institutional Review Boards, Surveys, and Social Science Research. Constance F. Citro, Daniel
R. Ilgen, and Cora B. Marrell (eds). Committee on National Statistics and Board on Behavioral, Cognitive, and
Sensory Sciences. Washington, DC: The National Academies Press. Available:
http://books.nap.edu/catalog.php?record_id=10638 [accessed 12 June 2007],
NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
Housing-Related Health Hazards Involving Children. Committee on Ethical Issues in Housing-Related Health
Hazard Research Involving Children, Youth and Families, Bernard Lo and Mary Ellen O'Connell (eds). Board on
Children, Youth, and Families, Division of Behavioral and Social Sciences and Education and Institute of Medicine.
Washington, DC: The National Academies Press. 216 pp. Available:
http://books.nap.edu/catalog.php?record_id=11450 [accessed 12 June 2007],
Resnik DB, Wing S (2007). Lessons learned from the Children's Environmental Exposure Research Study. Am J
Public Health 97(3):414-8.
U.S. EPA (U.S. Environmental Protection Agency) (2000) Comments on the Use ofDatafmm the Testing of Human
Subjects: A Report by the Science Advisory Board and the FIFRA Scientific Advisory Panel. U nilcd States
Environmental Protection Agency, Science Advisory Board, EPA-SAB-EC—017. s
U.S. HHS (U.S. Department of Health and Human Services (1993). The Institutional Review Guidebook. Office for
Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.hlm [accessed 12 June 2007],
Van Belle G, Fisher L, Heagerty P, Lumley T (2004). Biostatistics: A Methodology for the Health Sciences (2nd
Edition). New York, NY. John Wiley & Sons, Inc.
Wackerly D, Mendenhall W, Scheaffer R (2001). Mathematical Statistics with Applications (6th Edition). Pacific
Grove, CA: Duxbury Press.
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SECTION 3
Ensuring Protection of Vulnerable Groups
Concern for the protection of vulnerable groups is fundamental to modern ethical thought
and guidelines. The Belmont Report was "meant to provide broad principles that could be used
to generate specific rules and regulations in response to [U.S.] research scandals such as
Tuskegee and Willowbrook.12 It focuses on informed consent, favorable risk-benefit ratio, and
the need to ensure that vulnerable populations are not targetedfor risky research" (emphasis
added; Emanuel et al., 2000).
The Common Rule requires IRBs to assure that "additional safeguards have been
included in the study to protect the rights and welfare of these [vulnerable] subjects'' [at 40 CFR
26.111(b) in CFR, 2006a], If an observational human exposure study includes vulnerable
research participants, it is essential that the investigators be cognizant of the special issues and
requirements of research involving vulnerable populations. Researchers have to justify the
involvement of vulnerable populations in the research study and include the appropriate
safeguards for protection of their safety and welfare. The Common Rule protections are
discussed further in the IRB guidebook (HHS, 1993). EPA regulations include not only the
general protections for vulnerable populations found in the Common Rule (Subpart A) but also
define additional protections for children and for
pregnant or nursing women (and their fetus or
nursing child) in Subparts B, C, and D (CFR,
2006a).
The section begins by identifying or defining
vulnerable groups and then discusses ethical issues
that may be important in conducting observational
exposure studies involving those groups, especially
children and pregnant women. The discussions about
the ethical issues are based largely on EPA's human
subjects regulations and on the recommendations
from the CIOMS document, International Ethical
Guidelines for Biomedical Research Involving
Human Subjects (CIOMS, 2002).
3.1 Identification of Vulnerable Groups
In the U.S. human subjects regulations (45
CFR 46 and 40 CFR 26) do not formally define
vulnerable populations. Instead, the Common Rule
gives examples of potentially vulnerable groups.
(See Text Box 3-1.) In addition, the Department of
Health and Human Services (HHS) extends added human subjects protections to pregnant
12 For more information about these and other research scandals, see Ethical and Policy Issues in Research Involving
Human Participants, Vol. /, Report and Recommendations of the National Bioethics Advisory Commission,
Bethesda, MD, August, 2001. See p. 153 for information about the Willowbrook State School experiments. The
report is available at www.bioethics.gov/reports/past commissions/nbac human part.pdf [Accessed September 3,
2007],
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Text Box 3-1. Potentially Vulnerable Groups
• Children
• Pregnant women (and their
fetuses)
• Nursing women (and their
Common Rule: Ex- neonates)
amples of Vulner- •Prisoners
able Groups • Handicapped persons
(40 CFR 26) • Mentally disabled persons
• Economically disadvantaged
persons
• Educationally disadvantaged
persons
EPA Extends strin-
gent protections to
these groups
(40 CFR 26)
HHS Extends addi-
tional protections to
these groups
(45 CFR 46)
Additional Vulner-
able Groups in NIH
training materials
Children
Pregnant women (and their
fetuses)
Nursing women (and their
neonates
Children
Pregnant women & fetuses
Nursing women & neonates
Prisoners
The terminally ill,
Students and employees
Comatose patients
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women, human fetuses, neonates, prisoners, and children as vulnerable groups (45 CFR 46,
Subparts B, C, and D, see CFR, 2006b). Analogous but somewhat more stringent protections for
children, pregnant or nursing women, and fetuses are specified in Subparts B, C, and D of the
EPA Rule (40 CFR 26). The regulations do not preclude other groups from being considered
vulnerable, however, and the National Institutes of Health (NIH), in its Human Participant
Protections Education for Research Teams online tutorial (NIH, 2002), lists students or
employees and terminally ill or comatose patients
as potentially vulnerable groups. .
As used in this document, vulnerable
persons are those who are relatively (or
absolutely) incapable of protecting their own
interests. Vulnerability refers to a substantial
incapacity to protect one's own interests owing to
such impediments as lack of capability to give
informed consent, lack of alternative means of
obtaining medical care or other expensive
necessities, or being a junior or subordinate
member of a hierarchical group. Vulnerable
persons may have insufficient power, intelligence,
resources, strength, or needed attributes to protect
their own interests (CIOMS, 2002). (See Text Box
3-2.) Because of their incapacity to protect their
own interests, ethically perceptive researchers will
plan and implement special provisions for the
protection of the rights and welfare of the
vulnerable persons.
3.2 Justification for Involving Vulnerable Persons in Observational Studies
The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40
CFR 26.111(a)(3)] and instructs the IRB to consider the "purposes of the research and the setting
in which the research will be conducted." CIOMS goes further and recommends that "Special
justification is required for inviting vulnerable individuals to serve as research subjects"
(Guideline 13, CIOMS, 2002).u
13 In the commentary on Guideline 13 in CIOMS (2002), the committee states that:
The central problem presented by plans to involve vulnerable persons as research subjects is that such plans
may entail an inequitable distribution of the burdens and benefits of research participation. Classes of indi-
viduals conventionally considered vulnerable are those with limited capacity or freedom to consent or to de-
cline to consent. They are the subject of specific guidelines in the CIOMS document (Guidelines 14, 15) and
include children, and persons who, because of mental or behavioral disorders, are incapable of giving in-
formed consent. Ethical justification of their involvement usually requires that investigators satisfy ethical
review committees that
•the research could not be carried out equally well with less vulnerable subjects;
•the research is intended to obtain knowledge that will lead to improved diagnosis, prevention or treatment of
diseases or other health problems characteristic of, or unique to, the vulnerable class—either the actual sub-
jects or other similarly situated members of the vulnerable class;
•research subjects and other members of the vulnerable class from which subjects are recruited will ordinar-
ily be assured reasonable access to any diagnostic, preventive or therapeutic products that will become
available as a consequence of the research;
•the risks attached to interventions or procedures that do not hold out the prospect of direct health-related
benefit will not exceed those associated with routine medical or psychological examination of such persons
unless an ethical review committee authorizes a slight increase over this level of risk (Guideline 9); and,
34
Text Box 3-2. Potentially Vulnerable Groups
Identified in International Guidance
(Guideline 13, Council for International Organi-
zations of Medical Sciences. 2002)
• Junior or subordinate members of a hierarchical group;
examples include employees, students, members of
the armed forces, police, and others who work for, or
closely with re-searchers; they may have expectations
of preferential treatment if they agree to participate or
fear of disapproval or retaliation if they refuse to par-
ticipate in a study. f~%
• Elderly persons, who may acquire attributes that define
them as vulnerablea/vith advancing age.
• Residents of nursing homes.
• People receiving welfare benefits or social assistance.
• People with low or no incomes (poor and unemployed).
• Homeless persons.
• Nomads.
• Refugees or displaced persons.
• Some ethnic and racial minority groups.
• People with incurable diseases (in clinical studies).
• The politically powerless.
» Members of communities unfamiliar with modern medi-
cal concepts (applies to clinical studies)
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CIOMS recommendations, although written to address biomedical research, also are
generally applicable to observational human exposure studies. The authors of this document
consider the CIOMS requirement that that the research could not be carried out equally well with
less vulnerable subjects to be particularly important. EPANERL researchers should include
vulnerable groups in observational exposure studies only if their participation is critical to the
success and applicability of the research. Even then, EPA and NERL researchers will have to
meet stringent standards for protecting the rights and safety of the vulnerable participants. For
example, EPA regulations governing observational research with children are even more
stringent than the CIOMS Guideline. If such research does not hold out the prospect of direct
benefit to the child, no increase whatsoever over minimal risk is permitted.
3.3 Minimal Risk and Vulnerable Groups
EPA has codified protections for children, pregnant or nursing women, and fetuses in
Subparts B, C, and D of the EPA human subjects rule (40 CFR 26). Subpart B strictly prohibits
research involving intentional exposure of children or pregnant or nursing women (and,
therefore, exposure of her fetus).
EPA's regulations do allow for observational research involving fetuses and pregnant
women (40 CFR 26 Subpart C) or children (40 CFR 26 Subpart D) but with additional
protections in place and with strict limitations on research that presents more than minimal risk14
(CFR, 2006a). When considering vulnerable groups, The Institutional Review Board Guidebook
(HHS, 1993) states that "IRBs should therefore determine whether the proposed subject
population would be more sensitive or vulnerable to the risks posed by the research as a result of
their general condition or disabilities. If so, the procedures would constitute more than minimal
risk for those subjects."
When conducting observational human exposure studies, it is recommended that
researchers consult these regulations and guidebooks. NERL researchers also will need to ensure
that all of the requirements in Subparts B, C, and D of the EPA Human Subjects Rule are met.
3.4 Research Involving Children
Children have long been recognized as a vulnerable group in research studies. EPA and
HHS both extend special protections to children (CFR,
2006a,b). There are many books, reports, and research
manuscripts that specifically address issues associated
with research involving children (e.g., NRC & IOM,
2005; IOM, 2004; Kodish, 2005; NRC, 2003; AAP, 2003)
CIOMS has drafted guidelines for including
children in biomedical research (Guideline 14, CIOMS,
2002). The guidelines require an investigator to provide
the assurances shown in Text Box 3-3 before undertaking
research involving children.
The participation of children in some
observational studies is critical to characterizing
children's exposures to chemicals in the environment. It is
•when the prospective subjects are either incompetent or otherwise substantially unable to give informed
consent, their agreement will be supplemented by the permission of their legal guardians or other appropri-
ate representatives.
14
Minimal risk is defined at 40 CFR 26.102(i) and again at 40 CFR 402(g). It "means that the probability and mag-
nitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily
encountered in daily life or during the performance of routine physical or psychological examinations or tests."
35
Text Box 3-3. Assurances Required by
CIOMS Before Research Involving
Children May Begin
¦ the research might not equally well be carried
out with adults;
¦ the purpose of the research is to obtain
knowledge relevant to the health needs of
children;
¦ a parent or legal representative of each child
has given permission;
¦ the agreement (assent) of each child has
been obtained to the extent of the child's
capabilities; and
¦ a child's refusal to participate or continue in
the research will be respected.
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well recognized that children are not "little adults" and that their exposures to chemicals differ
(and in some cases are higher) from those of adults. Children are behaviorally and
physiologically different from adults. Their interaction with their environment, through activities
such as playing on floors, mouthing of hands and objects, and handling of food, may increase
contact with contaminated surfaces. Children have proportionately higher breathing rates,
relative surface area, and food intake requirements that also may increase exposure. Differences
in absorption, metabolism, storage, and excretion may result in higher biologically effective
doses to target tissues. Immature organ systems may be more susceptible to toxicological
challenges. Windows of vulnerability, when specific toxicants may permanently alter the
function of an organ system, are thought to exist at various stages of development. Because the
factors influencing children's exposures to chemicals are not well characterized (Cohen Hubal et
al., 2000), it is sometimes important that observational studies involve children.
Because they are so vulnerable, there has long been concern about including children in
research studies, and biomedical research often excluded children. However, in recent years,
there has been concern that excluding children from research is not ethical. NIH has a Policy and
Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects
(NIH, 1998) whose goal is to increase participation of children in research. The policy of NIH is
that children have to be included in all human subjects research, conducted or supported by NIH,
unless there are scientific and ethical reasons not to include them. Proposals or applications to
NIH for research have to present an acceptable justification if children will be excluded from a
research study. Of course, as discussed above, if the research topic is irrelevant to children, the
CIOMS guidelines would recommend that they be excluded from the research.
Observational human exposure studies conducted by NERL are not expected to involve
greater than minimal risk. It will be the responsibility of the NERL researchers to present
adequate information for the IRB to demonstrate that the research does not involve greater than
minimal risk. Researchers designing observational research studies should carefully evaluate the
risks and benefits specific to their study and the participants involved. In developing the study
design and human subjects protocols, researchers need to ensure that the protocols ensure the
protection of the rights and welfare of the participant children, and that risks and harm are
minimized. The perception of risks and benefits, both by the individual and by the family or
community, may influence the risk/benefit determination. It may prove useful for the research
team to consult with other experienced researchers who have conducted similar studies and with
members of the IRB to ensure that the information included in the human subjects research
protocol is adequate for the IRB s review.
It is recommended that researchers consider all of the potential issues associated with
involvement of children in their studies in developing the study design and research protocols,
including the role of the family. EPA's human subjects rule for observational research not
involving greater than minimal risk to children (40 CFR 26.404) (i.e., the kinds of observational
exposure studies that NERL exposure research is likely to entail) focuses on obtaining assent of
the children and permission of their parents or guardians. But the role of the family goes far
beyond their involvement in the informed consent process. In observational human exposure
studies, even when children are the participants, the parents or guardian play a key role in the
collection of data and information during the study. For studies with very young children, family
members supply all of the information relevant to the child. NERL researchers need to ensure
that both the child and the parents or guardians and other caregivers are fully informed and are
willing participants. Without their willing participation, the research cannot be successful.
3.5 Women as Research Subjects
Women are routinely included as research participants in observational human exposure
studies. However, pregnant women and their fetuses are vulnerable groups and require special
36
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protections. EPA's human subjects rule prohibits intentional dosing studies and provides
additional controls for observational research (40 CFR 26, Subparts B and C).
CIOMS (2002) includes two guidelines for biomedical research involving women as
research subjects. The first of these, number 16, states that women should not be excluded from
biomedical research because of the potential for becoming pregnant during a study. The
document continues, "A general policy of excluding from such clinical trials women biologically
capable of becoming pregnant is unjust in that it deprives women as a class of persons of the
benefits of new knowledge derived from the trials." The second CIOMS guideline, number 17,
asserts that, if involved in a research study, pregnant women should be fully informed, and
included only if the research benefits pregnant women and is thoroughly supported by reliable
evidence in animal studies.
Although the CIOMS guideline specifically addresses biomedical research, the ethical
concepts behind the guidelines may be generally applicable to observational exposure studies.
EPA's human subjects rule is completely consistent with the HHS rule in adding additional
protections for pregnant women and fetuses involved in observational research (40 CFR 26.304
and 45 DFR 46.204). The U.S. Federal human subject rules reflect requirements that are similar
to the CIOMS recommendations by adding additional protections to include previous studies that
assess the risk to pregnant women and fetuses [subparagraph (a)]; scientific necessity (providing
benefit to the woman or fetus, or developing "important biomedical knowledge which cannot be
obtained by any other means") [subparagraph (b)]; "any risk is the least possible for achieving
the objectives of the research" [subparagraph (c)]; plus others.
3.6 Other Potentially Vulnerable Groups
HHS specifies additional protections for prisoners as a potentially vulnerable group in
Subpart C of 45 CFR 26. Additional requirements for other vulnerable groups in research studies
are not specifically defined in either EPA's or HHS' human subjects rules. Nonetheless, other
groups (as discussed above in Section 3.1) may be considered to be vulnerable and, as such, may
warrant additional consideration and protection as required in the Common Rule. For these other
potentially vulnerable groups, such as employees, students, handicapped persons, mentally
disabled persons, and economically or educationally disadvantaged persons, nursing home
residents or otherwise incapacitated elderly, etc., the Common Rule requires researchers and
IRBs to fully evaluate the protocols to ensure that the safety and welfare of the groups will be
protected.
3.7 References
AAP (American Academy of Pediatrics Committee on Environmental Health) (2003). Pediatric and Environmental
Health. (2nd Edition). Elk Grove Village, IL: American Academy of Pediatrics.
CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection
of Human Subjects. U.S. Code of Federal Regulations. Available:
hllp://\\\\\\.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06.html [accessed 12 June 2007],
CFR (Code of Federal Regulations) (2006b). 45 CFR Subtitle A Department of Health and Human Services Part 46
Protection of Human Subjects. U.S. Code of Federal Regulations. Available:
http://www.access.gpo.gov/nara/cfr/waisidx_06/45cfr46_06.html [accessed 13 June 2007],
CIOMS (The Council for International Organizations of Medical Sciences) (2005). Special Ethical Considerations
for Epidemiological Research. Superseded by International Ethical Guidelines for Epidemiological Research
(Discussion Draft No. 3, April 2007). World Health Organization. Geneva, Switzerland. Available:
http://www.cioms.ch/070516april_epi_revisions.pdf [accessed 12 June 2007],
37
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40
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CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines
for Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007],
Cohen Hubal EA, Sheldon LS, Burke JM, McCurdy TR, Berry MR, Rigas ML, Zartarian VG, Freeman NCG
(2000). Children's exposure assessment: a review of factors influencing children's exposure, and the data available
to characterize and assess that exposure. Environ Health Perspect 108(6):475-486.
Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 20:2701-2711.
IOM (Institute of Medicine) 2004. Ethical Conduct of Clinical Research Involving Children. Marilyn J. Field and
Richard E. Behrman (eds). Washington, DC: The National Academies Press.
Kodish E (ed) (2005). Ethics and Research With Children—A Case-Based Approach. . New York. NY: Oxford
University Press.
NB AC (National Bioethics Advisory Commission) (2001) Ethical and Policy Issues in Research Involving Human
Participants, Volume /, Report and Recommendations of the National Bioethics Advisory Commission, Bethesda,
MD, August 2001. Available: www.bioethics.gov/reports/past commissions/nbac human parl.pdf [accessed 3
September 2007],
NIH (National Institutes of Health) (2002) Human Participant Protections Education for Research Teams [online
tutorial]. Available: http://cme.cancer.gov/clinicaltrials/learning/humanparlicipanl-protections.asp [accessed 12 June
2007],
NIH (National Institutes of Health) (1998). NIH Policy and (iuidc'lines on The Inclusion of Children as Participants
in Research Involving Human Subjects. Available: hllp://granls.nih.gov/grants/guide/notice-files/not98-024.html
[accessed 13 June 2007],
NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
Research. Panel on Institutional Review Boards. Surveys, and Social Science Research. Constance F. Citro, Daniel
R. Ilgen, and Cora B. Marrell (eds). Committee on National Statistics and Board on Behavioral, Cognitive, and
Sensory Sciences. Washington, DC: The National Academies Press. Available:
http://books.nap.edu/catalog.php?record_id= 10638 |acccssed 12 June 2007],
NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
Housing-Related Health Hazards Involving Children. Committee on Ethical Issues in Housing-Related Health
Hazard Research Involving Children. Youth and Families, Bernard Lo and Mary Ellen O'Connell (eds). Board on
Children, Youth, and Families. Division of Behavioral and Social Sciences and Education and Institute of Medicine.
Washington, DC: The National Academies Press. 216 pp. Available:
http://books.nap.cdu/catalog.php?rccord_id=11450 [accessed 12 June 2007],
U.S. HHS (U.S. Department of Health and Human Services) (1993). The Institutional Review Guidebook. Office for
Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm [accessed 12 June 2007],
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SECTION 4
Privacy, Confidentiality, and Other Concerns Related
to Observational Human Exposure Studies
Observational human exposure studies are designed to describe people's contact with
pollutants as they go about their everyday lives. Of necessity then, observational studies take
place in the locations that participants often consider to be personal and private. Clinical research
studies generally are conducted in a research facility, a clinic, a hospital, or some other
institutional or medical setting. Survey research may be conducted by mail, over the phone, or in
another "neutral" setting. But, observational human exposure studies are conducted in the
participants' "personal" environment—their home, daycare center, school, vehicle, workplace, or
other environments that people occupy during their routine daily activities. This difference in the
research setting means that researchers involved in observational human exposure studies have
an even greater challenge in meeting the ethical obligation to respect the privacy of the
participants.
When exposure science researchers like those at NERL enter a home to carry out their
studies, the "expectations and constraints may be strikingly different than when research is
carried out in a medical setting" (p. 64, NRC & 10M, 2005). The legal precept of freedom from
unreasonable search and seizure, and the historic and deeply rooted principle that "a man's home
is his castle" contribute to a belief in of the "sanctity of the home" (see the discussion on pp. 62-
66, NRC & IOM, 2005).
The joint NRC & IOM report, Ethical
Considerations for Research on Housing-Related
Health Hazards Involving Children, discusses the
ethical issues associated with entering a participant's
home to conduct research and explores the
researchers' responsibilities that derive from
conducting research in people's homes (NRC &
IOM, 2005). These housing-related discussions are
particularly relevant to observational human
exposure studies which often include environmental
and biological measurements in people's homes or
personal locations. Many of the topics identified in
that report are discussed in this section. (See Text
Box 4-1.)
4.1 Privacy Issues
Privacy refers to an expectation that a person is free from intrusion into personal matters
and is free from the presence or view of others. The Institutional Review Board Guidebook
defines privacy as "control over the extent, timing, and circumstances of sharing oneself
(physically, behaviorally, or intellectually) with others" (HHS, 1993). Beauchamp and Childress
find that the right to privacy is based on the principle of respect for autonomy. "We often respect
persons by respecting their autonomous wishes not to be observed, touched, or intruded upon.
... A loss of privacy occurs if others use any of several forms of access, including intervening
in zones of secrecy, anonymity, seclusion, or solitude" (pp. 295-296, Beauchamp and Childress,
2001).
Text Box 4-1. Topics in Section 4
Privacy Issues
Confidentiality
Confidentiality of Information
Confidentiality of Participation
Collateral Observations
Potential Non-study Hazards in the Residence
Collateral Observations with Mandated Reporting
Requirements
Hazard Communication
Planning and Staff Training
Third-Party Issues
Determining Whether a Third Party is a Human
Subject
Informing Third Parties of Research Activities
Research Results and Third Parties
Data and Safety Monitoring and Oversight
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Although research participants may agree to allow researchers to enter their home or
other zone of personal space to conduct their research measurements, they have not abrogated
their right to privacy. "When individuals voluntarily grant others some form of access to
themselves, their act is an exercise of the right to privacy, not a waiver of that right" (p. 297,
Beauchamp and Childress, 2001). Researches should remember that they are guests in the homes
for a specific purpose. "When people visit a home, there are social expectations about what is
acceptable behavior. People who are invited into a home are expected to be sensitive to and
respectful of the host's customs and values." (p. 65, NRC & IOM, 2005).
By their very nature, observational studies encroach on the privacy of a research
participant. Entry in a participant's home (or other personal zones) does represent a loss of
privacy, but researchers should be careful to ensure that their presence does not become a
violation of the individual's right to privacy. The relationship between the researcher and the
participant may be complicated, and there may be conflicts between the researcher's role and
their ethical obligations (NRC & IOM, 2005). In entering a participant's personal space, it may
be difficult, or impossible, to avoid making observations unrelated to the research question,
thereby further intruding on the participant's personal privacy. Indeed, there may be ethical and
legal obligations for the researchers to respond to those observations. Beauchamp and Childress
suggest that "policies carefully specify the conditions of access that will and will not count as a
loss of privacy or a violation of the right to privacy. The policy should accurately define the
zones that are considered private and not to be
invaded, and should also identify interests that
legitimately may be balanced against privacy
interests" (Beauchamp and Childress, 2001).
Observational studies also may infringe on
the privacy of other individuals, for example, other
members of the participant's family or household.
Researchers should strive to minimize the
intrusion and loss of privacy and to show respect
for the privacy of study participants and third
parties at all times. It is incumbent on the
researcher to recognize privacy issues in the
design and implementation of the research study.
The NRC & IOM report suggests that researchers
anticipate the ethical issues that arise from
conducting research in a person's home, and that
they take steps to correct them (1) by thinking
through the issues as part of the study design; (2)
by discussing the issues during the informed
consent process; and (3) by ensuring that the
frontline staff that enter into a participant's home
"understand their role as members of the research
team, how that role differs from the role of
neighbor or friend, and how they should respond
when they make observations that are not part of the
4.2 Confidentiality
Confidentiality and privacy are not the same thing. Confidentiality refers to limits on the
dissemination of information disclosed by a person in a special professional relationship, such as
the doctor-patient relationship or the participant-researcher relationship (Beauchamp and
Childress, 2001). The Institutional Review Board Guidebook defines confidentiality as "pertains
40
Text Box 4-2. Privacy Issues
• Researchers should develop an anticipatory plan for
flow to deal with privacy issues during the study. The
plan should include a list of potential observations that
could be of concern and a plan for how they will be
handled.
• The plan needs to address both the legal and ethical
obligations of the researcher in response to situations
where privacy is compromised.
• Privacy issues will vary depending on the culture of the
population being studied. What one individual or group
may find as an invasion of privacy, another group may
not have a concern about.
• Privacy issues involve individual participants and may
extend to third parties, including the community.
• Researchers may find a meeting with community rep-
resentatives to learn about the community residents
and potential privacy issues to be helpful. Community
representatives can help the researcher identify poten-
tial privacy issues and offer advice on how to ad-dress
them.
• Research may wish to respect the privacy of occupants
sharing the study participant's household or other
study locations by providing advance notification of
study visits and by giving them the opportunity not to
be present during those visits.
• Field staff should be trained on how to minimize
breaches of privacy and how to handle privacy issues.
• The informed consent process and form has to address
how the researcher will handle privacy issues such as
collateral observations of household hazards
protocol" (p. 66, NRC & IOM, 2005).
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to the treatment of information that an individual has disclosed in a relationship of trust and with
the expectation that it will not be divulged to others without permission in ways that are
inconsistent with the understanding of the original disclosure" (HHS, 1993). Emanuel et al. state
that one way to respect the privacy of the participants is "by managing the information in
accordance with confidentiality rules" (p. 2707, Emanuel et al, 2000). Confidentiality in research
also may extend to limiting dissemination of the knowledge that an individual is participating in
a research study.
As part of the research planning process, researchers are responsible for developing
procedures to protect confidentiality and to define limits on the researcher's ability to provide or
protect confidentiality. Explaining plans or procedures for protecting confidentiality and their
limits15 to prospective research participants is an integral part of the informed consent process.
4.2.1 Confidentiality of Information
Many types of information may be
collected in observational human exposure studies.
Information may be collected through
questionnaires, staff observations of residential or
other environments, diaries, personal sample
collection, environmental or residential sample
collection, and collection of biological specimens.
Measurement data from the collected samples
become part of the information for a participant.
The specific information to be obtained to address
the research questions should be determined in the
development of the study design and research
protocol.
Disclosure of information that can be
linked to an individual may cause harm or distress
to that individual. Researchers are responsible for
developing safeguards to protect the
confidentiality of information and physical samples collected from research participants. (See,
for example, Guideline 18, ClOMS, 2002.) 16
Researchers also should be aware that certain combinations of information from a study
may sometimes lead to the indirect identification of the individual. Certain combinations of
demographic information, for example, may make it relatively simple to identify an individual.
Precise geographic location information may be sufficient to pinpoint a residence. Researchers
' " Beauchamp and Childress discuss when—for example, because of risks to others evidenced by biomarkers of in-
fectious disease, etc.—one may be ethically justified in infringing on an individual's privacy and confidentiality (pp.
293-312. Bcauchamp and Childress, 2001). They also discuss similar ethical issues that may arise in regard to ge-
netic data. ClOMS Guideline 18 (CIOMS, 2002) provides suggestions for safeguarding or disclosing genetic infor-
mation. If exposure scientists collaborate with medical researchers or epidemiologists and obtain such information,
they need to be cognizant of the relevant ethical issues and of the CIOMS guidelines.
16 Guideline 18 states "The investigator must establish secure safeguards of the confidentiality of subjects' research
data. Subjects should be told the limits, legal or other, to the investigators' ability to safeguard confidentiality and
the possible consequences of breaches of confidentiality." Additional CIOMS commentary on the confidentiality
guideline states: "Confidentiality between investigator and subject. .. . Prospective subjects should be informed of
limits to the ability of researchers to ensure strict confidentiality and of the foreseeable adverse social consequences
of breaches of confidentiality. Some jurisdictions require the reporting to appropriate agencies of, for instance, cer-
tain communicable diseases or evidence of child abuse or neglect. .. . These and similar limits to the ability to main-
tain confidentiality should be anticipated and disclosed to prospective subjects."
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Text Box 4-3. Approaches for Protecting
Personally-Identifiable Information
• • Developing procedures for safeguarding information
prior to collecting the information
• Ensuring that data or samples are anonymous by not
collecting or by destroying identifying information or
linkages
• Restricting access to identifying information to only
those requiring access
• Assigning codes to participants, data, and samples
rather than using identifiers
• Physically separating identifying information and link-
| age files from other study information
I « Securing identifying information in locked files with
| limited access
I • Restricting identifying information from computers that
I are networked with other computers or electronic sys-
I terns
I • Restricting identifying information from computers that
I are not kept in secure locations with limited access
I • Training research staff members on human subject
J protection and on information security procedures
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may use several strategies to reduce the likelihood of indirect identification when study results
are reported.
• Redact from publications, reports, or public data sets information that might be used to
indirectly identify a research participant.
• Generalize exact information; for example, replace birth date with age or year of birth or
classify age as part of a range.
• Aggregate information across individuals; for example, only report data in cells of sufficient
size to make individual linkages unlikely.
• Reduce the specificity of geographic coordinate information to a level that a specific residence
or other location can not be identified.
Another step that can help protect confidentiality is to obtain a Certificate of
Confidentiality. Certificates of Confidentiality are issued by NIH to protect identifiable research
information from forced disclosure. They allow the investigator and others who have access to
research records to refuse to disclose identifying information on research participants in any
civil, criminal, administrative, legislative, or other proceeding, whether at the Federal, State, or
local level. Certificates of Confidentiality may be granted for studies collecting information that,
if disclosed, could have adverse consequences for subjects or damage their financial standing,
employability, insurability, or reputation. By protecting researchers and institutions from being
compelled to disclose information that would identify research subjects, Certificates of
Confidentiality help achieve the research objectives and promote participation in studies by
assuring confidentiality and privacy to participants. Any research project that collects personally
identifiable, sensitive information and that has been approved by an IRB is eligible for a
certificate. Federal funding is not a prerequisite for a certificate. A Certificate of Confidentiality
does not diminish, however, the investigator's need to protect the personally identifiable
information as described above.
4.2.2 Confidentiality of Participation
In some types of research, the knowledge that a person is participating in a particular
research study could, potentially, put the participant at risk for harm or distress. This topic is
discussed in The Institutional Review Board Guidebook, with special emphasis on behavioral and
social research that deals with sensitive topics (HHS, 1993). The guidebook describes the need
for additional safeguards to protect and prevent disclosure of the identity of participants,
including the use of Certificates of Confidentiality for sensitive matters.
Observational human exposure studies often pose particular challenges with regard to
limiting dissemination of the knowledge of an individual's participation in the study. Visiting the
research participant's residence to collect samples or to make observations will necessitate
informing other family members or occupants about the visit and study procedures. Research
participants may be asked to wear personal monitors over time periods ranging from a day to a
week or more. Wearing these devices in public places, schools, or workplaces may identify them
as a study participant or generate questions regarding the activity. Field staff visits to the
participant's home or setting up outdoor sample collection devices around the home also might
disclose their participation. And, in some cases, third parties outside of the home have to be
asked for permission or be informed that monitoring activities are taking place.
Researchers and IRBs should consider whether knowledge of an individual's
participation by others might create potential for harm or distress in an observational human
exposure study. Such risks might be limited to possible discomfort in attracting unwanted
attention; this may be particularly true for adolescents. However, in some cases, the potential
risks could be greater, for example, in cases where participation could provoke an adverse
reaction from a landlord or employer. Oftentimes study protocols can be structured to minimize
these potential risks. Through the informed consent process, prospective participants should be
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made aware of the limits of the researcher's ability to protect knowledge of their participation in
the study and of the possible risks of disclosure.
4.3 Collateral Observations
In the course of conducting an observational human exposure study, research staff may
observe potentially unsafe conditions or situations that are unrelated to the research study. Such
"collateral observations" may involve physical hazards in the study participant's residential
environment or evidence of situations, such as child abuse, that have to be reported to proper
authorities. In preparing for the research study, it is recommended that researchers carefully plan
for possible collateral observations, including their identification, staff training, and hazard
communication and reporting. This may be a major element in the data and safety monitoring
and oversight for the study. The informed consent process should reflect procedures used to
manage collateral observations. Potential participants should be informed of situations in which
confidentiality might be breached, such as statutory requirements for reporting abuse or
imminent harm to self or others.
4.3.1 Potential Non-Study Hazards in the Residence
Research staff conducting observational human exposure studies often will spend time in
and around study participant residences. In the course of visiting a residence or conducting
study-related observations, research staff may observe potential hazards unrelated to the research
being performed. Some hazards may be associated with the potential for physical injury, whereas
others may be related to exposure to chemical or biological agents. Some situations may be
potential hazards only for young children, whereas other conditions may present potential
hazards for all residents or occupants.
The NRC & IOM recommend that researchers
should consider such foreseeable observations and
potential hazards in advance, develop responses to the
risks, and submit the proposed plans to the IRB for review
to ensure that they are appropriate "in the context of the
research and the affected community." The NRC & IOM
also advise that field staff should be trained in how to
assess and respond to such risks (Recommendations 7.3
and 7.4, NRC & IOM, 2005). For other behaviors and
risks that have not been specifically identified in advance,
procedures should be included in the data and safety
monitoring and oversight provisions of the study design
and research protocol to address these issues. The
fundamental ethical principle of beneficence would
motivate researchers who observe serious harms to take steps to try to prevent those harms, even
for observations that are not directly related to the study. The steps that they may take can range
from immediate action to prevent an imminent and serious danger to statutory reporting of
observations (see Section 4.3.2 below) to reporting the observation to the data and safety
monitoring and oversight authority for advice on how to respond (see Section 4.5 below). (The
reader is also referred to pages 59-61 and 134-144 of NRC & IOM [2005] report for a more
thorough discussion of researchers' responsibilities in such cases.)
4.3.2 Collateral Observations with Mandated Reporting Requirements
Some collateral observations may have statutory requirements for reporting to designated
authorities. Examples of such observations include
• observed child or elder abuse or evidence of such abuse or neglect,
i I
Text 4-4. Potential Hazards that Might
Be Encountered in a Residential
Environment
| • Unsecured firearm |
| • Uncovered electrical outlets J
| • Unprotected stairways |
• Missing child-protective cabinet latches f
• Lack of window guards f
| • Missing or inoperable smoke alarm I
I • Housing code violations ?
| • Chipping or flaking paint - potential for lead f
exposure in older homes f
I • Malfunctioning or un-vented combustion J
| appliances - potential for CO exposure |
• Unsecured poisons or other dangerous prod-
I ucts I
| • Excessive mold growth |
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• statements or actions of intent to harm self or others, and
• certain communicable diseases
Because different reporting statutes often pertain in different states, it is necessary for
researchers to learn and understand the applicable reporting requirements for the study location.
In the case of abuse, it is also important to understand what actions or situations are considered
abusive in a particular state. Although direct physical harm or violence might be obvious to a
research staff member, there are other conditions of neglect that might be more difficult to
recognize or to know when to report.
4.3.3 Hazard Communication
It is difficult for researchers to determine when and how to communicate with study
participants or third parties about collateral observations related to potential hazards. A hazard
might present such an imminent threat to health or safety that staff would need to communicate
immediately with the participant or take action to mitigate the threat. In some cases, such as
instances of abuse with attendant statutory reporting requirements, it may be necessary to breach
confidentiality. More often, however, a potential hazard identified as a result of collateral
observation may not be an imminent threat or pose a potential risk that is situation-dependent or
is related to third parties. A number of considerations in hazard communication come into play
regarding confidentiality, privacy, the ability of the researcher to provide accurate and effective
information regarding the hazard and hazard mitigation, and the ability of the study participant or
others to effectively mitigate the hazard without unintended adverse consequences. The National
Academy of Science Committee on Ethical Issues in Housing-Related Health Hazard Research
Involving Children, Youth, and Families discussed many of these issues in depth (NRC & IOM,
2005).
Different communities, cultures, or demographic groups can have different risk
perceptions, which may affect how collateral observations are assessed and reported from one
study location to the next. The American Academy of Pediatrics Committee on Environmental
Health has prepared information regarding perception, identification, and communication of
environmental health risks (AAP, 2003). Researchers likely will benefit from including
community members on the research team in developing the study design and research protocol
or from consultation with community boards regarding identification of hazards and hazard
communication.
It is important that any advice that the researcher might provide to study participants
regarding hazard mitigation should be carefully considered. Considerations in recommending an
action may include whether the mitigation approach has been shown to be effective, whether the
study participant can understand and effectively implement the action, and whether unintended
adverse consequences might result from taking an action. In some cases, it may be reasonable to
refer the participant to another organization that can provide expert advice or assistance.
4.3.4 Planning and Staff Training
As part of the study planning process and protocol development, it is important that
researchers be cognizant of the kinds of collateral observations that might occur in the
implementation of the study protocol and to develop plans as to how such observations would be
handled. Researchers may choose to include a systematic approach in hazard identification, such
as using a home-hazard checklist that becomes an ancillary part of the study protocol.
Alternatively, collateral observations could be handled on a case-by-case basis.
Staff experience and training is a critical consideration for managing collateral
observations. Staff members that visit study participant residences may not have expertise or
experience in identifying many of the potential hazards without adequate training. It is especially
important to consider staff experience and training in hazard communication. Consistency in
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communication is very important, and researchers may decide to use materials prepared by other
organizations that have expertise regarding a particular hazard.
Researchers and IRBs will need to work together to determine how best to maintain
participant privacy and confidentiality while meeting obligations to research participants
regarding hazards identified through collateral observation. The informed consent process is
likely to be a key element in informing participants about how collateral observations will be
handled. Potential participants should be informed of situations in which confidentiality might be
breached, such as statutory requirements for reporting abuse or imminent harm to self or others.
It is recommended that the informed consent process include any procedures or plans for
identifying and reporting on hazards not directly related to the research question.
4.4 Third-Party Issues
• Third-party issues can arise in observational human
exposure studies in two ways. First, the study may
collect limited information about or related to
individuals other than the study participants. Second,
study activities may affect or involve people or
organizations other than the study participants.
Examples of activities that may involve or affect
third parties in observational human exposure studies
could include, but are not limited to the following:
• Asking the participant about demographic, occupational,
smoking, or product use information for other household members
• Collecting residential environmental samples in multiperson households
• Collecting environmental samples in common areas of multifamily housing units
• Collecting personal or environmental samples in a day care, school, health care, or
occupational setting
• Measuring chemical occurrences or concentrations that may be of interest or import to other
household members or to the community
• Collecting activity or dietary information about a community
It is important for researchers and research staff to understand whether and to what extent
the research involves or affects third parties, and how third-party involvement might affect the
study participants. Study planning; IRB review; and communication before, during, and after the
study can take third-party issues into account.
4.4.1 Determining Whether a Third Party is a Human Subject
It is up to the IRB to determine whether a third party is a human subject afforded human
subject protections under the Common Rule. A third party would meet the Common Rule
definition of a human subject [40 CFR 26.102(f)] if individually identifiable private information
about them is collected (CFR, 2006). When this occurs, the informed consent of the third party
must be obtained, or, if certain criteria are met, the IRB may determine that informed consent
may be waived. It can be difficult to determine whether information about a third party is both
individually identifiable and private. Discussions of this issue and recommendations for
determining whether third-party information is identifiable and private have been submitted to
the Office of Human Research Protections of HHS by NIH (2001) and the National Human
Research Protections Advisory Committee (NHRPAC)(2002).
Whether or not a third party is determined to be a human subject, the researcher should
treat research information about a third party as confidential.
I Text Box 4-5. Potential Third-Parties
In Exposure Studies
• Household members not enrolled in the study
• Relatives |
• Care givers for children or elders
• School staff,,
• Employers
• Other members of the community
• Building managers or facility operators
| • Landlords
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4.4.2 Informing Third Parties of Research Activities
Obtaining permission from or informing third parties of certain types of activities may be
needed in some observational human exposure research studies. For example, household
members living with a study participant need to be informed about home study visits and
residential sample collection activities. Study activities that occur outside of the participant's
home or yard may require informing or gaining permission from third parties. A study may
include collection of environmental samples (i.e., ambient air, dust, soil) from outdoor common
areas of multifamily housing where the study participant lives. Issues regarding privacy,
permission, and incentives for third parties in housing-related studies have been discussed in the
NRC & IOM (2005) report.
Observational studies also may include cases when study participants are asked to collect
personal samples (i.e., wearing a personal air monitor) over a time period that includes time they
spend in a school, day care, or workplace. Such monitoring might require informing or gaining
permission from an organization's staff or an employer. In each case, the researcher and IRB
have to consider whether obtaining permission from or informing a third party is appropriate
and, if so, to define the procedures for doing so. The researcher and IRB have to also consider
the potential impact of third-party knowledge of research activities on confidentiality and risk for
the study participant and have to ensure that it is clearly and fully explained in the informed
consent process.
4.4.3 Research Results and Third Parties
Prior to initiating a research study, researchers should consider whether research results
may be provided to third parties. In some studies, there may be reasons to inform household
members living with a study participant about specific residential measurement results. In
community research studies, aggregated or summary research results may provide a benefit to
the community. In this case, it would be beneficial to seek out the advice of community
representatives regarding results reporting prior to the study. Researchers also should determine
whether there are State or local reporting requirements for some types of measurement results
above specified action levels (i.e., blood-lead levels, heavy metal concentration in soil). It is
important that the researcher and IRB ensure that confidentiality and privacy of study
participants are carefully considered in any case where reporting study results to third parties is
contemplated or may be required. Ideally, the informed consent process would make clear
whether, under what conditions, and how research results might be provided to third parties.
4.5 Data and Safety Monitoring and Oversight
The Common Rule requires for IRB approval that, "When appropriate, the research plan
makes adequate provision for monitoring the data collected to ensure the safety of subjects." [40
CFR 26.1 1 1(a)(6)],
Data and safety monitoring plans (DSMPs) are developed and applied in all clinical trial
research studies. Clinical trials are prospective studies designed to answer specific questions
about the effects or impact of particular biomedical or behavioral interventions. The DSMPs are
used to insure the safety of participants, the validity of data, and appropriate termination of
studies for which significant benefits or risks have been uncovered or when it appears that the
trial cannot be concluded successfully (NCI, 2001). Depending on the study scope and potential
risks and benefits, a data safety monitoring board (DSMB) may be created to assess procedures
for data and safety monitoring and to independently assess safety and outcomes on an ongoing
basis during the study.
Formal independent monitoring boards or committees, like DSMPs, have not seen
widespread use in observational studies, although much of the information included in DSMPs
often has been captured in the research protocols. Researchers and IRBs may, however, consider
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using monitoring and oversight boards to help assure participant safety and research integrity in
observational human exposure research, particularly in complex longitudinal studies and in
studies that include vulnerable subjects.
At least two NIH institutes have developed guidelines for monitoring and oversight in the
observational research that they sponsor.
(1) The National Heart Lung and Blood Institute (NHLBI) has developed an interim policy on
the creation and role of observational study monitoring boards (OSMBs) for observational
research sponsored by that institute (NHLBI, 2007). OSMBs may be established for large or
complex observational studies on a case-by-case basis. The role of the OSMB is "to help
assure the integrity of the study by closely monitoring data acquisition for
comprehensiveness, accuracy, and timeliness; and monitoring other concerns such as
participant confidentiality."
(2) The National Eye Institute (NEI) has developed guidelines for data monitoring and oversight
committees (DMOCs) for observational research (NEI, 2001). The role of the DMOC is to
"assist the NEI and the study investigators in protecting the interests of study participants and
in preserving the integrity and credibility of the study."
When appropriate, formal procedures for routine monitoring of scientific and ethical
issues will need to be incorporated into observational research and approved by the IRB to
ensure participant safety and the integrity of the research. Even though most observational
human exposure research is considered low-risk, there is often a need to determine whether
appropriate threshold values for biological or environmental levels of chemicals exist or can be
determined that, if the threshold value is exceeded, it would trigger reporting or other actions.
The safety of measurement procedures and equipment also has to be considered. Unanticipated
adverse events also may be encountered in some types of observational studies. Participant
consent and understanding of the research effort, participant recruitment, participant retention,
and data accuracy and quality should all be monitored to ensure the scientific integrity of
research results.
The authors already have discussed (Section 2.8) the needs (1) to establish, in advance,
criteria and standards for monitoring the research program in regard to both scientific and ethical
issues; (2) to establish who will monitor and oversee the research progress (the monitoring and
oversight authority, be it an individual, team, or review committee); and (3) to establish the roles,
responsibilities, and authorities of the researchers and of the monitoring and oversight authority.
The planning also should include steps to meet the Institute of Medicine recommendations that
researchers should "anticipate risks and behaviors that may be observed in the home . . . [and]
develop anticipatory plans that specify how to assess and respond to risks when they are
identified, and educate their staffs about the plan" (Recommendation 7.3, p. 144, NRC & IOM,
2005).
Once the procedures and organization for monitoring and oversight of the observational
study are approved by the IRB, it is the responsibility of the researchers and of the monitoring
and oversight authority to ensure that the planned actions are implemented. Implementation of
the monitoring and oversight function may include the following.
• Ensuring that procedures for identifying, reporting, and responding to anticipated or
unanticipated adverse events and safety issues are in place and are being followed
• Assessing and responding to risks when they are identified
• Evaluating the performance and knowledge of the staff regarding identification of potential
risks and the actions they should take
• Implementing procedures for monitoring the informed consent process, participant behaviors,
participant recruitment, participant retention, procedures to protect privacy and confidentiality,
and other human requirements for adherence to the research protocol and compliance with
ethical standards and with EPA's human subjects rules
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• Ensuring that measurements and samples are collected as planned, and that data are reported
on a timely basis
• Evaluating whether the observed measurements exceed the pre-established threshold values
and, if so, ensuring that reporting procedures and plans to respond to the potential risks are
completed on a timely basis
• Ensuring that quality assurance plans that define procedures for assessing and ensuring study
protocol compliance are being met
• Ensuring data quality targets are met through independent internal or external auditing
requirements
• Taking all warranted oversight actions to ensure the safety of the participants and the integrity
of the study, including terminating the research study if appropriate
/
4.6 References
AAP (American Academy of Pediatrics Committee on Environmental Health) (2003). Pediatric and Environmental
Health. (2nd Edition). Elk Grove Village, IL: American Academy of Pediatrics.
Beauchamp TL, Childress JF (2001). Principles of Biomedical Ethics. New York. NY: Oxford University Press.
CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I—Environmental Protection Agency Part 26
Protection of Human Subjects. U.S. Code of Federal Regulations. Available:
http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06.html |accessed 8 August 2007],
CIOMS (Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
http://www.cioms.ch/frame_guidelines_nov_2002.htm |acccssed 12 June 2007],
Emanuel EJ, WendlerD, Grady C (2000). What Makes Clinical Research Ethical'.' .JAMA 20:2701-2711.
NCI (National Cancer Institute) (2001). EssentialBlements of a Data and Safety Monitoring Plan for Clinical Trials
Funded by the National Cancer Institute. Available: hllp://www3 .cancer, gov/rrp/dsm ess.html [accessed April
2007],
NEI (National Eye Institute) (2001). National Eve Institute Guidelines for Data Monitoring and Oversight of
Observational Studies. Available: http://www.nei.nih.gov/funding/datastudies.asp [accessed April 2007],
NHLBI (National Heart Lung and Blood Institute) (2007). Monitoring Boards for Data and Safety (Interim Policy).
Policy effective date: 14 May 2007. Available: http://public.nhlbi.nih. gov/ocr/home/GetPolicv.aspx?id=8 [accessed
September 2007],
NHRPAC (National Human Research Protections Advisory Committee) (2002). Clarification of the status of third
parties when refePmced by human subjects in research. Available:
http:/A\ w w.hlis. gov/ohrp/nhrpac/documents/third.pdf [accessed April 2007],
NIH (National Institutes of Health) (2001). Protection of third party information in research: Recommendations of
the National Institutes of Health to the Office for Human Research Protections. Available:
http://www.nih.gov/sigs/bioethics/nih third party rec.html [accessed March 2007],
NIH (National Institutes of Health) (1998). NIH Guide: NIH Policy for Data and Safety Monitoring. Available:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html [accessed April 2007],
NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
Housing-Related Health Hazards Involving Children. Committee on Ethical Issues in Housing-Related Health
Hazard Research Involving Children, Youth and Families, Bernard Lo and Mary Ellen O'Connell (eds). Board on
Children, Youth, and Families, Division of Behavioral and Social Sciences and Education and Institute of Medicine.
Washington, DC: The National Academies Press. 216 pp. Available:
http://books.nap.edu/catalog.php?record_id=11450 [accessed 12 June 2007],
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2 U.S. FDA (U.S. Food and Drag Administration) (2001). Draft Guidance for Clinical Trial Sponsors on the
3 Establishment of Clinical Trial Data Monitoring Committees. U.S. Department of Health and Human Services, Food
4 and Drag Administration, Rockville, MD. Available: http://www.fda.gov/cber/gdlns/clindatmon.pdf. [accessed April
5 2007],
6
7 U.S. HHS (U.S. Department of Health and Human Services) (1993). The Institutional Review Guidebook. Office for
8 Human Research Protections. Available: www.hhs.gov/ohrp/irb/irb guidebook.htm [accessed 12 June 2007],
9 .
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SECTION 5
Creating an Appropriate Relationship Between
the Participant and Researcher
In observational human exposure studies, the researcher and the participant routinely
interact with each other, often in the participant's home or other private setting and often
repeatedly over several days. The nature and setting of the interactions mean that exposure
researchers should give special consideration to the many scientific and ethical issues that shape
the relationship between participants and the researchers. In these studies, it is recommended that
a strong relationship, built on openness and trust, should be developed between the researcher
and participant. The nature of that relationship and the ethical principles underpinning an
appropriate relationship are the focuses of this section of the document.
This relationship should be established on the ethical values of respect for the
participant's autonomy and respect for their welfare. Emanuel and his co-authors find that these
two ethical values translate into specific responsibilities for an ethical researcher in regard to
informed consent and respect for potential and enrolled subjects (Emanuel et al., 2000). They
describe the ethical principles for these responsible actions thusly, "Respect for potential and
enrolled subjects is justified by multiple principles including beneficence, nonmaleficence, and
respect for persons. Permitting subjects to withdraw and providing them additional information
learned from the research are key aspects of respecting subject autonomy. Protecting
confidentiality and monitoring well-being are motivated by respect for persons beneficence, and
nonmaleficence." Section 4 already has described some of the particular concerns regarding
privacy, confidentiality, and other issues related to observational studies. This section further
describes elements of the relationship between researchers and participants that are important to
consider and address during design and implementation of a study.
Of course, the relationship between the researchers and the individual participants does
not exist in isolation. The researcher-participant relationship may influence, and be influenced
by, the relationship with the community in which the participant lives. Good, two-way
communications are critical for the development and nourishment of an appropriate researcher-
participant relationship. Although those two topics are the subject of the next sections of this
document, elements from those topics will unavoidably color the discussions in this section also.
5.1 Informed Consent
In observational human exposure studies, informed consent ensures that the participant
understands the range of risks associated with participation and the voluntary nature of
participation and provides essential protections to the participant. The three "pillars" of informed
consent are (1) information; (2) comprehension; and (3) voluntary participation, or
"voluntariness" (U.S. DHEW, 1979/ Informed consent requires "provision of information to
subjects about the purpose of the research, its procedures, potential risks, benefits, and
alternatives, so that the individual understands this information and can make a voluntary
decision whether to enroll and continue to participate" (Emanuel et al., 2000).
The NRC & IOM document, Ethical Considerations for Research on Housing-Related
Health Hazards Involving Children (NRC & IOM, 2005), contains a comprehensive and very
useful discussion of informed consent procedures and requirements in Chapter 6. The IOM
report, Responsible Research: A Systems Approach to Protecting Research Participants, also
includes a thoughtful discussion of participant-investigator interactions and the informed consent
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process (IOM, 2002). CIOMS also includes recommendations for both the process and content of
informed consent (CIOMS, 2002). The reader should refer to those documents for additional
information about this topic.
Federal regulations governing research
that is either Federally conducted or Federally
funded (i.e., all human subjects research at
NERL) are codified in the Common Rule. The
regulations set forth requirements for both the
content of an informed consent and the process
for obtaining and documenting an individual's
informed consent. General regulatory
requirements for the elements of informed
consent are codified in the Common Rule at 40
CFR 26.116(a)(l)-(8) (CFR, 2006). The
regulations also prescribe the use of a written
consent form and describe how informed
consent is to be documented (at 40 CFR
26.117). The regulatory requirements for
informed consent highlight a number of issues
that a NERL researcher needs to consider in
developing and administering the informed
consent process and the consent form
document. The discussion of these issues,
arising from regulatory requirements or
identified in recent writings on ethical
considerations in human subjects research, is
grouped below, under the three pillars of
informed consent: (1) information, (2)
comprehension, and (3) voluntary
participation.17
Text Box 5-1. Common Rule Requirements:
Elements of Informed Consent
(1) An explanation of the purposes of the research
(2) The expected duration of the subject's participation
(3) A description of the procedures to be followed and
identification of any experimental procedures
(4) A description of any reasonably foreseeable risks or
discomforts to the subject
(5) A description of any reasonably expected benefits to the
subject or others
(6) A disclosure of appropriate alternative procedures that
might be advantageous to the subject;
(7) A description of the extent that confidentiality will be
maintained
(8) For research involving more than minimal risk, an
explanation about whether compensation or medical
treatments are available if injury occurs
(9) An explanation of whom to contact with questions about the
research or to report a research^related injury
(10) A statement that participation is voluntary, refusal to
participate will involve no penalty, and the subject may
discontinue participation at any time without penalty or loss
of benefits to which the subject is otherwise entitled
) A statement that the particular treatment or procedure
may involve risks to the subject (or to the embryo or fetus,
if the subject is or may become pregnant) which are
currently unforeseeable
(12") Anticipated circumstances under which the subject's
participation may be terminated by the investigator without
regard to the subject's consent
(13*) Any additional costs to the subject that may result from
participation in the research
(14*) The consequences of a subject's decision to withdraw
from the research and procedures for orderly termination of
participation by the subject
(15*) A statement that significant new findings developed
during the course of the research that may relate to the
subject's willingness to continue participation will be
provided to the subject.
(16*) The approximate number of subjects in the study
* Included if appropriate [40 CFR 26.116(b)]
(11
5.1.1 Information
Some items that researchers should keep in mind as they provide information to the study
participants are summarized below. These items may be based on regulatory requirements or
currently may be recommendations as ethical "best practices."
• The information "shall be in language understandable to the subject" (40 CFR 26.116). This
may require forms to be written and administered in different languages during a study. For
example, the National Children's Study (NCS) plans to produce all consent materials in
English and Spanish, with other translations made available as needed (NCS, 2007).
• Information may be presented orally in addition to an appropriately written document (40 CFR
26.117). Participants often find discussions with research staff more useful than written
consent forms (p. 103, NRC & IOM, 2005). The NCS plans to pilot test an interactive,
computer-based audio/video consent tool and to compare it with traditional written informed
consent approaches (NCS, 2007).
17 An IRB may waive informed consent under some very limited conditions. See 40 CFR 26.116(c) and (d).
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• The explanation of the purpose of the research and description of the study procedures should
be written at a level that the participant can understand.18 The National Institutes of Health
recommend writing consent forms as "plain language documents that explain the research in
an honest, straightforward way" and suggest that doing so will help enhance public trust
(Recommendation 11, NIH, 2005).
• The consent form should contain sufficient information to describe the study procedures, but
not so much information that it causes confusion and results in the participant not
understanding the study. There is not agreement on what the appropriate level of information
is. IRBs do not agree on the level of information; some require lengthy descriptions of the
study, whereas others prefer concise information. Ultimately, the IRB dictates the language of
the informed consent document and the researcher will need to comply. It will benefit the
researcher to discuss the consent process with their IRB when they develop the consent form
document and process (p. 108, NRC & IOM, 2005).
• In observational studies, information about the risks of the hazards being studied needs to be
conveyed to the participants during the consent process. The importance of the failure to do
this was highlighted in the Grimes v. Kennedy Krieger case. Information should be provided to
the study participant on what hazards pertinent to the topic of the study may be present in the
participant's environment, particularly those microenvironments being studied, what hazards
will continue to exist in those microenvironments after the research is completed, and how
those hazards may adversely affect the participant's health (NRC & IOM, 2005).
• The informed consent process should describe whether any study results will be provided to
participants and, if so, how and when (p. 101, NRC & IOM, 2005).
• For studies involving children as participants, it generally is regarded as desirable that the
informed consent be discussed with and obtained from both parents if possible. However,
under both the EPA Rule at 40 CFR 26.406(b) (for observational research with children) and
the HHS Rule at 45 CFR 46.408(b) (for all research with children), if the IRB determines that
the research involves no more than minimal risk or holds out the prospect of direct benefit to
the child, the IRB may decide that the permission of one parent is sufficient. Under the EPA
Rule, greater than minimal risk observational research with children that does not hold out the
prospect of direct benefit to the child is not permitted under any circumstances. Under the
HHS Rule, greater than minimal risk research in children without the prospect of direct benefit
is permitted in very limited circumstances, but the consent of both parents is required in those
cases (unless one parent is deceased, unknown, incompetent, or not reasonably available, or
when only one parent has legal responsibility for the care and custody of the child).
• For studies involving children as participants, it is desirable for those children with sufficient
capacity to be involved in the consent process. Moreover, it is generally accepted that the
child's assent be obtained whenever this is developmentally possible and otherwise
appropriate. Under both the EPA Rule and the HHS Rule, the IRB is responsible for
determining that adequate provisions have been made for soliciting the assent of the children
when, in the judgment of the IRB, the children are capable of providing assent. Assent,
however, may be waived in those restricted circumstances in which consent may be waived
18 A survey of IRBs found that their readability standards ranged from 5th-grade level to lOth-grade level (Paasche-
Orlow et al. 2003). Interestingly, the same report found that 92% of the time, the sample consent forms provided by
the IRBs did not meet their own readability standards. The NRC & IOM report (p. 107, NRC & IOM, 2005)
discusses a National Cancer Institute (NCI) effort to simplify informed consent forms that uses text targeted for 8th-
grade reading level. More information about the NCI template may be found at
www.nci.nih.gov/clinicaltrials/understanding/simplification-of-informed-consent-docs/page2. [Accessed September
12, 2007],
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under the Common Rule. Those circumstances and the required IRB documentation are
described in the Common Rule at 40 CFR 26.116(d).
• The consent form should clearly state that participation is voluntary and that study participants
may "discontinue participation at any time without any penalty or loss of benefits to which the
subject is otherwise entitled" [US 40 CFR 26.116(a)(8)], If a subject chooses to withdraw from
a study, the consequences of their decision and the process for orderly withdrawal should be
clearly explained [US 40 CFR 26.116(b)(4)],
• The consent form should address any foreseeable potential future use of samples and data
(CIOMS, 2002). For example, effects of environmental exposures on gene expression are
potentially very important. Therefore, biologic specimens for DNA analysis may be obtained
from participants in future studies. But, it is recognized that human genomic data are private,
intimate, and sensitive, and they create special concerns about the potential for discrimination,
stigmatization, and impact on future employment or insurance. The informed consent process
needs to explain what the plans may be for such specimens and recognize the rights of the
subjects to decide about any such future use, including having the material destroyed. The
informed consent process needs to explicitly discuss obtaining permission from participants on
behalf of themselves and their child to obtain specimens for genetic analysis.
5.1.2 Comprehension
Research participants frequently fail to understand the research protocols to which they
agree to participate (NRC & IOM, 2005). In considering the ethical issues raised by the Grimes
v. Kennedy Krieger case, the NRC & IOM committee "realized that the crucial issue regarding
consent was not what information was contained in the consent forms, but rather what the
parents understood about the study and the hazards present in the home before and after the
study" (p. 19, NRC & IOM, 2005). The committee laments that "IRBs place their attention on
consent forms rather than on the process of providing and discussing information" (p. 103, NRC
& IOM, 2005). The IOM recommends that "the informed consent process should be an on-going,
interactive dialogue between research staff and research participants involving the disclosure and
exchange of relevant information, discussion of that information, and assessment of the
individual's understanding of the discussion" (Recommendation 4.1, IOM, 2002). These
comments emphasize how important true two-way communication is to comprehension, the
second pillar in the informed consent process.
The following items are a variety of issues concerning comprehension thatNERL scientists
should keep in mind as they develop an informed consent process in collaboration with the
research team, the IRB and other peer reviewers, and EPA's HSRRO. These items may be based
on regulatory requirements or may simply be recommendations as ethical "best practices."
• Researchers need to assume responsibility for developing an interactive dialogue with
participants for the exchange and discussion of relevant information as a part of the informed
consent process, not just for conveying information. The dialogue should be ongoing,
continuing throughout the research project (IOM, 2002).
• The consent form and its content are only one part of the overall consent process. An equally
important part is how information is conveyed to the participant outside of the written form
itself. Participant comprehension is contingent on all elements of a comprehensive consent
process that involves ongoing information exchange between researchers and participants, as
well as a written informed consent document (NRC & IOM, 2005).
• The most effective way to improve comprehension is by talking one-on-one with study
participants. "Having a study team member or a neutral educator spend more time talking one-
on-one to study participants appears to be the most effective way of improving research
participants' understanding" (Flory and Emanuel, 2007).
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• The explanation of the purpose of the research and description of the study procedures should
be written at a level that the participant can understand (NRC & IOM, 2005).
• The researcher should describe the benefits of participation in the study [40 CFR
26.116(a)(3)], but should not promise any outputs or outcomes that he or she cannot deliver.
Participants often misunderstand the purpose of the research. The researchers should also
attempt to reduce the likelihood of therapeutic misconception19 or related misunderstandings in
which the participant anticipates a benefit that does not really exist, such as reduction of the
hazard in an observational study (NRC & IOM, 2005).
• The administration procedure should include some test of the participants to demonstrate that
they truly understand the information that is being conveyed (IOM, 2002).
• Tools to assess comprehension have been developed, but, as described in NRC & IOM (2005),
there are no standard mechanisms for assessing comprehension. Tests for appropriate grade-
level language can be performed, but additional comprehension testing should be considered
as well (Flory and Emanuel, 2004).
• Researchers need to develop innovative approaches to improve comprehension. Multimedia,
such as video or graphics, may be used but have had limited success in the past (NRC & IOM,
2005; Flory and Emanuel, 2004). TheNCS currently is developing a highly sophisticated
video consent tool that may be able to serve as a model going forward. The video presentation
will include embedded questions to assess the participant's understanding of the key elements
of the NCS and what their participation will involve (NCS, 2007).
5.1.3 Voluntary Participation
The third pillar of informed consent is voluntary participation. The Belmont Report
emphasizes that participants "should understand clearly the range of risk and the voluntary
nature of participation" [Emphasis added.] The ethical principles of respect for persons and their
autonomous decisions morally obligate the researcher to ensure that an individual's decision to
participate in a human research study is truly voluntary and uncoerced (Emanuel et al., 2000). A
number of study elements may affect whether the participant's actions are truly voluntary.
• Remuneration and incentives may have undue influence and are discussed below.
• Access to study-dependent benefits or care that would otherwise not normally be received may
impair voluntariness.
• Voluntary participation also may be compromised when there is an existing relationship
between the researcher and participants, such as employer/employee or teacher/student.
• Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
including children, prisoners, handicapped persons, mentally disabled persons, and
economically or educationally disadvantaged persons, or members of the military, for
example. When research participants come from such groups, additional protections to insure
voluntariness in the context of the research may be required (see also 40 CFR 26, Subparts B,
C, and D and 45 CFR 46, Subparts B, C, D).
• Whether payments will lead to a coerced decision to participate often is difficult to determine
without input from people from similar socioeconomic backgrounds as the participants (p.
Ill, NRC & IOM, 2005). Researchers should work with community representatives to
develop a consent process that will be maximally effective in providing information, ensuring
19 "Therapeutic misconception" is a term that refers to an inaccurate understanding on the part of a research
participant that a direct therapeutic benefit will be provided by virtue of participation in a clinical trial. Researchers
performing observational exposure studies should be aware of the potential for misunderstandings to arise that are
analogous to the misunderstanding represented by the therapeutic misconception. Ensuring comprehension of the
study and its expected results is important to this issue.
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and documenting comprehension, and ensuring that participation is voluntary. (Also see
Section 6.)
Researchers should remember that obtaining informed consent should be "an on-going,
interactive dialogue . . . involving the disclosure and exchange of relevant information" (IOM,
2002): it is not simply having a consent form signed. The process is most effective when the
researcher spends time with potential participants to discuss the study and to answer questions.
5.2 Payments to Research Participants
The decision whether to pay research participants, including the appropriate level of
payment,20 is a complex ethical issue. Payment and other forms of remuneration are not to be
used as undue inducement for participants to assume research risks that they would not otherwise
accept. On the other hand, it may be appropriate to offer reasonable remuneration in some
research studies. The difficulty for researchers and IRBs is that there is often little clear and
uniform guidance for determining what constitutes "undue inducement" or "reasonable"
remuneration for any particular research study, population, and level of risk. Additional
considerations regarding payment to participants arise when working with vulnerable
populations, including children.
5.2.1 Regulations and Guidance Regarding Payment to Research Participants
There is little specific guidance regarding payments or other forms of remuneration in
Federal human research regulations. The Common Rule and additional human subjects
protections do not directly address payments to research participants but the regulations do
discuss providing additional safeguards for subjects vulnerable to coercion or undue influence
[40 CFR 26.111(b)], The NIHIRB guidebook advises IRBs to determine whether the rewards
offered for participation in research constitute undue influence (HHS, 1993). According to the
IRB guidebook undue inducement might blind prospective subjects to risks, impair their ability
to exercise proper judgment, or may cause people to lie or to withhold information that would
make them ineligible to enroll or continue participation.
The U.S. Food and Drug Administration (FDA) has provided guidance for investigators
and IRBs for clinical research studies (FDA, 1998). The guidance states that "payment to
research subjects for participation in studies is not considered a benefit, it is a recruitment
incentive." FDA expects payments to accrue as the study progresses and not to be contingent on
completing the study, although a "small proportion as an incentive for completion of the study is
acceptable." The guidance is concerned with the issue of coercion or undue influence, and it
recognizes the IRB as the responsible party for deciding what is or is not acceptable.
CIOMS also provides guidance and commentary on this issue in the International Ethical
Guidelines for Biomedical Research Involving Human Subjects (2002). Guideline 7 and the
associated commentary emphasize that payments to subjects for expenses incurred because of
their participating in a research study are legitimate. The guideline also allows payment for
inconvenience and time spent, so long as the payments or other direct benefits are not "so
extensive as to induce prospective subjects to consent to participate in research against their
better judgment."
The approaches of HHS, FDA, and CIOMS above are consistent in not considering
payments to be a benefit to research participants when considering risks versus benefits. All of
20 This document uses the terms payment, remuneration, or compensation interchangeably. In general, these terms
refer to money or other items that "are given to acknowledge the time and inconvenience of participating in research
or to reimburse participants for any costs they incur. The term compensation is often used in the context of
compensation for research-related injuries" (p. 112, NRC & IOM, 2005). The authors occasionally refer to
compensation for research-related injuries, but the text should make it clear when they do.
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the guidelines recognize the legitimacy of some recompense, but they are all concerned with the
issue of undue influence. "Payments or rewards that undermine a person's capacity to exercise
free choice invalidate consent" (CIOMS, 2002), and voluntariness is a pillar of legitimate
informed consent.
There are many research articles that address issues associated with compensating
research participants (for example, Ackerman, 1989; Dickert et al., 2002; Erlen et al., 1999;
Emanuel, 2004; 1999; Fry et al., 2005; Grady et al., 2005; litis et al., 2006; NRC & IOM, 2005;
IOM, 2004; Russell et al., 2000;
VanderWalde, 2005; Wendler et al.,
2002; Weise et al., 2002). A number of
specific issues and concerns regarding
participant payments have been
identified. On the other hand, many
researchers and ethicists argue that it is
often appropriate to provide reasonable
payment. The principles of "justice,
fairness, and gratitude support payment
to those who bear the burdens of
research on behalf of society" (NRC,
2004). There are a variety of ethical
and justified reasons for compensating
research participants. Text Box 5-2
lists some of the concerns and the
reasons for remuneration of
participants.
IRBs have considerable discretion with regard to payments and consider payments with
regard to the specific circumstances of the research and of the population being studied. The
issue of recompense can be a difficult but legitimate ethical issue involving weighing the
different ethical principles of justice and fairness against the concerns about undue influence and
the invalidation of consent. Ethical review committees, including IRBs, need to consider many
factors when determining when it is appropriate to offer payments to research participants and
the level and form of payments when they are appropriate. Review committees also should
consider how and when information on payments is communicated to prospective study
participants.
5.2.2 Types arid Amounts of Incentives or Remuneration Offered in Research
Studies
Payments or other forms of remuneration have been offered in a wide variety of study
types, ranging from clinical trials to behavioral and social research to observational human
exposure studies. Remuneration or incentives can take various forms, including monetary
payments (e.g., cash, gift certificates), nonmonetary payments (e.g., gifts, valuable information),
reimbursement for expenses associated with participating in the study, or nothing at all (e.g., the
altruistic approach).
Direct reimbursement may be made to participants for out-of-pocket expenses for costs
directly associated with participation in a study. These might include transportation costs,
parking fees, or child care costs. When remuneration for time and burden is provided, it is often
in the form of monetary payments. Different approaches may be considered for determining
reasonable amounts for remuneration, including a set payment for each visit, a small daily
payment, payment at the prevailing minimum hourly wage, or payment at some other hourly rate
appropriate for the community—perhaps a prevailing rate for unskilled labor (Emanuel et al,
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Text Box 5.2. Weighing the Issues About Remuneration
Concerns about Compensation
Payments may compromise
voluntary participation.
Participants may accept risks they
would not otherwise accept.
Participants may continue in a
research study beyond a point they
might ordinarily have withdrawn.
Payments may differentially
encourage research participation by
economically disadvantaged
people.
The offer of payments may cause
guardians or parents to not act in
the best interests of incompetent
persons or children in their care.
Persons in different circumstances
may view the same amount of
payment quite differently.
Payments may alter the composition
of the study sample and potentially
could compromise study integrity
Reasons for Compensation
> Recognizing participant
contributions to the research
and knowledge gained,
> Providing reimbursement for
direct and indirect participant
costs.
> Providing reasonable
remuneration for the time
f and effort associated with
participation in research,
%» and
> Providing incentives for
participation in studies with
low risk but no or few direct
benefits.
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2004). Incentives to encourage enrollment are sometimes used when participants will receive
little or no direct benefit from the research and can take the form of monetary or nonmonetary
payments. Incentives are kept modest so as not to impart undue influence. Researchers need to
consider the possible effects of incentive payments on the potential for differential recruitment
that could result in bias in the study sample.
Determining appropriate level of payments or incentives for participants in a research
study is complex. "No bright line distinguishes proper and reasonable payments to parents and
children from payments that are inappropriate" (p. 214, IOM, 2004). Many research
organizations and IRBs do not have written policies or guidelines regarding the determination of
reasonable payment. Decisions often are made based on the level of discomfort and burden, costs
to participants, and population characteristics. However, large differences in payment levels have
been found even in multisite studies in which the same protocol is administered across all sites.
Grady et al. (2005) performed a survey of practices for paying research participants in the
United States in Phase 1 to 4 clinical trials and physiologic, behavioral, and other types of
research. Across 467 studies of varying complexity that included payments, the median payment
was $155 (mean $266 ± $318, range $5 to $2000). The basis for dollar amounts was infrequently
described, with 19% of the payments based on time and 12% based on the procedures. In a
model of payment factors, studies with some prospect of therapeutic benefit, studies having at
least one invasive procedure, and studies with greater numbers of clinic visits were significantly
associated with higher dollar amounts. About 9.5% offered completion bonuses, and a similar
percentage offered escalating payments for follow-up study visits.
5.2.3 Payments When Children or Other Vulnerable Populations Are Involved
It is essential that special care be taken with regard to payments when members of
vulnerable populations are included in research studies. Vulnerable populations may include
children and adolescents, those with cognitive impairments because of medical conditions or age,
economically disadvantaged persons, and prisoners. These populations often are not capable of
making autonomous, fully informed decisions regarding risks and benefits, or they may be
particularly vulnerable to undue influence resulting from the offer of a payment for research
participation. In addition, payments made directly to parents or guardians could alter judgment
regarding the best interests of minor or incompetent persons in their care.
The ethical concern is that too high a payment may "undermine free and informed
consent by leading parents to expose their children to unacceptable risks" (NRC & IOM, 2005).
The NRC & IOM committee recognized that some commentators argued that children should
never be paid, and that parents ought not to be paid to enroll their children in research. Yet, on
balance, the committee felt that "reimbursement for expenses and some modest payment for time
spent in research activities is thus justified on the grounds of fairness" (p. 112, NRC & IOM,
2005).
Similarly, the IOM Committee on Clinical Research Involving Children found that
"certain types of payments to parents or adolescents are usually if not always acceptable, for
example, reimbursement for reasonable expenses that are necessary for research participation.
The specifics may vary, but examples of reasonable expenses are costs of transportation to the
research site, parking, lodging, meals, and babysitting. Other payments are never appropriate in
pediatric research, for example, paying parents for the use of their child in research" (pp. 225-6,
IOM, 2004). 21
21 The IOM Recommendation 6.2 states "In addition to offering small gifts or payments to parents and children as
gestures of appreciation, investigators may also—if they minimize the potential for undue influence—act ethically to
reduce certain barriers to research participation when they
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The IOM Committee recommends establishing policies on acceptable and unacceptable
types of payments. They also recommend that the policies disclose any recompense in a full and
open22 process while not over-emphasizing any recompense.
Although the NRC & IOM Committee on Ethical Issues in Housing-Related Health
Hazard Research Involving Children and the IOM Committee on Clinical Research Involving
Children both concluded that it is appropriate to reimburse expenses or compensate for time or
inconvenience, neither committee endorsed incentive payments to parents. In Europe, too,
incentive payments to induce parents to allow their children to participate in research are
unacceptable. The European Union requires that clinical trials on minors be undertaken only if
"no incentives or financial inducements are given except compensation" (European Parliament,
2001).
Payment for participation of children in research also is discussed in the literature.
Diekema (2005) emphasizes the need to ensure that payments do not distort parental decision-
making and do not tempt parents to consider other issues than the welfare of their child.
Similarly, Menikoff (2005) suggested that there need to be relatively robust protections in place
to ensure that families do not change their behaviors to participate in a study. He suggested that
these may include determining compensation as a percentage of a family's income and
developing criteria for documenting that behaviors have not changed to be eligible for
participation in a study. He suggested that, for a study of pesticides, potential study participants
provide documentation (such as receipts) that they routinely have been using a commercial
pesticide service. This may be difficult for potential participants to do if they do not save
receipts, and it would exclude all potential participants who purchase products and apply
pesticides themselves. This likely would affect the study objectives and generalizability of the
data collected. A survey of investigators (This et al., 2006) found that payments were made in
52% of the pediatric research studies surveyed, and that payment practices varied, as did the
reasons for decisions regarding payments. They found a range of payment values separated
across cash, gifts, items, vouchers, and other categories. A survey of IRBs (Weise et al., 2002)
found that payment for participation in research was allowed by 66% of responding institutions
but that many IRBs did not have specific policies, and that there was considerable variability
regarding the basis for decisions on payments in studies with children. The types of payments
included money, certificates, and bonds with large ranges in the amounts of payments for
• Reimburse reasonable expenses directly related to a child's participation in research
• Provide reasonable, age-appropriate compensation for children based on the time involved in research that does
not offer the prospect of direct benefit, and
• Offer evening or weekend hours, on-site child care, and other reasonable accommodations for parental work and
family commitments."
22 In recommending an open process, the IOM committee chose to reject the arguments from the American
Academy of Pediatrics that "any token payment to children for participating in research should not be discussed with
them until after research is completed for fear of unduly influencing their decisions (AAP, 2003).... On balance,
the committee agrees that it is best to mention token or other payments during the permission and assent processes"
(p. 215, IOM, 2004).
The IOM Recommendation 6.1 states "Institutional review boards, research institutions, and sponsors of research
that includes children and adolescents should adopt explicit written policies on acceptable and unacceptable types
and amounts of payments related to research participation. These policies should specify that investigators
• Disclose the amount, the recipient, the timing, and the purpose (e.g., an expense reimbursement or a token of
appreciation to a child) of any payments as part of the process of seeking parents' permission, and, as appropriate,
children's assent to research participation;
• Avoid emphasis on payments or descriptions of payments as benefits of participating in research during the per-
mission or assent procedures; and
• Obtain institutional review board approval for the disclosure of information about payments in advertisements
and in permission and assent forms and procedures."
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approved pediatric research. This research shows a lack of consistency and the need for guidance
and institutional policies that describe acceptable and unacceptable payments and the basis for
the amount of any payments.
The NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard
Research Involving Children described many of the ethical considerations, practices, and policies
regarding payments (NRC & IOM, 2005) for research conducted in the participants' homes,
rather than in a clinical facility. The research setting is similar to the setting of most
observational human exposure studies, and the Committee's commentary and recommendations
are also relevant. The Committee notes that it would be unfair to expect families to make
considerable sacrifices to participate in a time-consuming activity designed to advance
generalizable scientific knowledge, rather than benefit themselves directly, and that payment for
reimbursement of expenses and modest payment for time spent in research activities is justified
on the grounds of fairness. But the Committee then warns that if payments are too high, they
may distort parents' decisions about enrolling their children. The Committee also found that
"how the payment is made may also result in undue influence. For example, if payment for a
long-term follow-up study is made in a lump sum and only if the subjects complete the entire
study, then it could constitute an undue influence to stay in the study. If, on the other hand, the
money is paid weekly, the effect would not constitute an undue influence."
The NRC & IOM Committee recognizes that the issue of payment for participation in
research is controversial. They also discuss how "countervailing ethical guidelines" may
complicate the issues even more. Citing Wendler et al. (2002), the NRC & IOM Committee
points out that payments that are trivial for some families may be substantial for low-income or
disadvantaged families. "Yet to pay economically disadvantaged families less than more affluent
families for participating in the research is unfair because it requires similar sacrifices of time
and inconvenience from both" (p. 113, NRC & IOM, 2005). Similar ethical quandaries can arise
in multisite studies with differing costs for living. If the same payment is used in high-cost cities
as in low-cost areas, the payment may be inadequate to gain sufficient enrollment in the high-
cost area, whereas the same dollar amount may be "coercive" in the low-cost area. The NRC &
IOM Committee notes that a similar situation can arise when a study enrolls participants from
diverse socioeconomic backgrounds. There are social justice concerns that poorer people might
incur a disproportionate share of research risk and burden if payments induce unequal
participation rates in the population. Decisions regarding payment for research participation will
require careful consideration by IRBs when economically disadvantaged people may be enrolled.
Community advisory boards (CABs) can be very important in helping researchers and IRBs
determine what is appropriate with regard to payments within their community.
5.2.4 Payments in Observational Human Exposure Studies
Observational human exposure studies most often involve minimal risks to study
participants and few direct benefits, but may require considerable time and burden for
participation. Study requirements can include multiple in-home visits; the burden of wearing
personal air monitors for one or more 24-h period; preparing and providing duplicate diet
samples; collection of environmental samples inside and outside the home; completing
questionnaires, food diaries, and time/activity diaries; and providing urine, blood, saliva, or hair
samples. Monetary payments often have been included in these studies, with the level of
remuneration related to the number of study days or visits or the specific kinds of environmental
and biological samples and information that are collected or provided. Payment for direct
participant costs has been included in some studies, such as a reasonable payment for providing
researchers with duplicate diet samples.
NERL scientists should review the commentary and recommendations in the literature
before devising a payment program as part of a research protocol, especially the two recent
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National Academies of Science documents, Ethical Issues in Housing-Related Health Hazard
Research Involving Children (NRC and IOM, 2005) and Clinical Research Involving Children
(IOM, 2004). They should seek guidance from EPA's HSRRO to determine EPA's latest policies
and guidance in this regard. Input should also be sought from community representatives (for
example, those on the research team), especially to ensure that any payment is adequate to
compensate for expenses and reward participation, but that the payment is not so high as to
constitute undue influence or coercion in the community. If the study includes several follow-up
visits over a long term, NERL researchers should ensure that payment is made incrementally as
the NRC & IOM Committee suggested. NERL scientists should also adopt the IOM
Recommendations 6.1 and 6.2, including ensuring that any remuneration should be for
appropriate purposes and age-appropriate, and that the process should be open and fully
disclosed, while not overly emphasizing payments during the recruiting or informed consent
phases. The final decisions about the ethics of payments rest with the IRB, which will review,
modify as needed, and approve the research protocol, and with the EPA HSRRO, who has final
authority to approve, modify, or disapprove all of NERL's human subjects research efforts.
5.3 Research Rights and Grievance Procedures
Protecting the research rights of participants and providing independent access to
information regarding those rights and to grievance procedures is an important element in
developing and maintaining appropriate participant-investigator relationships. As part of the
informed consent process, the Common Rule requires [40 CFR 26.1 16(a)(7)], "An explanation
of whom to contact for answers to pertinent questions about the research and human subjects'
rights, and whom to contact in the event of a research-related injury to the subject."
Information about the research often can best be answered by the researcher. However, it
may benefit researchers and participants if information about the research can be obtained from
or confirmed by a trusted independent person or organization. Participants also need to know
how they can contact someone, independent from the researcher, who can answer questions
concerning the rights of research participants and provide information on grievance procedures
and research-related injuries. These questions could be addressed to the IRB, an ombudsman, an
ethics committee, or other knowledgeable administrative body. Consent documents are expected
to have at least two names with appropriate telephone contact information—one that can provide
information regarding the research and another that can provide information regarding their
rights as research participants.
5.3.1 Ombudsman
An ombudsman is a neutral independent advocate for research participants (and their
families or guardians, where applicable). Institutions and IRBs may recommend or require the
use of an ombudsman in certain types of research studies, particularly those seeking to study
vulnerable populations. Ombudsmen can fill several roles as participant advocates. They may be
an independent source of information regarding the study. They may be present during the
informed consent process to ensure that risks, benefits, and study requirements are
communicated correctly and understood by potential participants or their guardians. An
ombudsman may be used in studies involving prisoners or military personnel to ensure that there
is no coercion to participate. And the ombudsman may communicate problems or grievances
raised by research participants to the IRB and sponsoring organization.
5.3.2 Community Advisory Board
CABs can help ensure that participant rights are considered and addressed during the
study design and can play an important role in monitoring the research process. Community
members may choose to seek information about the study from the advisory panel, as an
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independent entity, before deciding whether to enroll. Representatives from such advisory boards
can be included in the research team that designs the study (see Section 2.3). The role of CABs is
more fully discussed in Section 6.
5.4 Creating a Supportive Environment for Research and Interaction
It is recommended that researchers and institutions strive to create a supportive
environment for research and interaction with research participants and communities. At the
personal level, this means researchers building trust with individuals and treating them with
respect. Following the IOM recommendations about the informed consent process—that it
"should be an on-going, interactive dialogue between research staff and research participants
involving the disclosure and exchange of relevant information, discussion of that information,
and assessment of the individual's understanding of the discussion" (Recommendation 4.1, IOM,
2002)—should go a long way in establishing a supportive environment with the individual
participants. At the community level, engagement of the community throughout the design,
conduct of the study, and follow-up will support trust-building and positive interactions.
Developing and providing this kind of support can be challenging in large-scale studies, and
particularly those that cross communities or are conducted across large geographic areas.
Institutions need to recognize the need for, and value of creating supportive research
environments by providing adequate funding because effective interaction takes considerable
time and effort.
Many of the factors that create a supportive environment for research participants are
described in the Report and Recommendations on Public Trust in Clinical Research for the NIH
Director from COPR (NIH, 2005). Although the advice from this workshop was developed in the
context of NIH-supported clinical research, many of the recommendations are applicable to
observational human exposure research and human subject research in general. A summary of
recommendations from the report is provided in Appendix C. The recommendations are focused
on the following areas.
Building trust through community partnerships,
Building relationships with patients [participants] (True partnerships with
patients may not be possible, but bidirectional relationships must be
enhanced.),
Building partnerships with community providers,
Building trust in scientists, and
Building trust in the [EPA] and scientific research.
5.5 Recruitment Strategies
Many strategies are used to select and recruit people into research studies requiring
human participation. The IRB is responsible for reviewing the selection process to ensure that it
is, above all, equitable. The requirement for IRB review is stated in 40 CFR 26.11 l(a)3.
Selection of subjects is equitable. In making this assessment, the IRB should
take into account the purposes of the research and the setting in which the
research will be conducted and should be particularly cognizant of the special
problems of research involving vulnerable populations, such as children,
prisoners, pregnant women, mentally disabled persons, or economically or
educationally disadvantaged persons.
The IRB guidebook is an excellent resource for consideration of concerns and elements
for equitable participant selection (HHS, 1993). It states that "Defining the appropriate group of
subjects for a research project involves a variety of factors—requirements of scientific design,
susceptibility to risk, likelihood of benefit, practicability, and considerations of fairness." The
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IRB guidebook raises a number of points to consider in the process for selection of human
participants. (See Text Box 5-3.)
Various participant recruitment
strategies may be used depending on the
type of research being performed and the
population of interest. Some of the common
approaches for identifying and making
initial contact with potential participants
include, but are not limited to
• direct telephone or in-person contact with
a person selected through a statistical
sampling process to obtain a
representative sample of the population
being studied;
• use of print or other media
advertisements, often used to recruit
people in a community with specific
characteristics;
• advertisement or word-of-mouth contacts through community groups, civic organizations, or
other types of organizations; and
• recruitment at physicians' offices, hospitals, and clinics or at churches, schools, or other social
institutions, either in person or through the use of advertisements or study brochures.
CABs can be consulted regarding proposed approaches for recruitment in community-
based research. All procedures and materials for participant recruitment are reviewed and
approved by the IRB prior to implementation. Some of the materials prepared for recruitment
might include the following.
• Recruitment scripts—prepared scripts used for in-person or telephone study information and
recruitment contacts
• Printed materials—brochures, flyers, letters, newspaper advertisements, and information
articles
• Audio/visual materials—radio and television scripts, video segments, public service
announcements
• Internet postings—study announcements and information, links to study materials, links to
related information
The IRB reviews all recruitment material to ensure that it does not adversely affect the
informed consent process, is consistent with the study protocol, and is likely to result in equitable
participant selection. IRBs will carefully consider how information regarding payment for
participation is presented to potential participants so as not to create undue influence.
Participant recruitment may be performed directly by the researcher or staff members of
the researcher's organization, or other individuals or organizations may be asked to recruit or
make initial informational contacts with potential participants. All persons involved in recruiting
must adhere to the procedures and materials approved by the IRB. It is recommended that
sponsoring organizations should not pay recruiters on a per-individual basis to minimize the
likelihood that individual recruiters will put undue pressure on potential participants to enroll.
5.6 Retention Strategies
Some observational human exposure studies require only a single visit or a single set of
visits with a participant over a relatively short time period (e.g., 24 h or 1 week). Other studies
may involve repeated interaction with participants over longer periods of time. Longitudinal
Text Box 5-3. IRB Guidebook Issues on Identifying
Subjects
1. Who will bear the burden? Who will reap the benefits?
2. Is there a disproportionate burden on any single group?
3. Is the proposed subject population required / justified?
4. Are there susceptible groups of people who should be excluded
from the research?
5. Are anticipate benefits distributed fairly? Do others have a
greater need to receive any of the anticipated benefits?
6. Are the research burdens distributed fairly?
7. Wll any special physiological, psychological, or social
characteristics of the subject group pose special risks for them?
8. Would it be possible to conduct the study with other, less
vulnerable subjects?
9. Has the selection process overprotected potential subjects who
are considered vulnerable {e.g., children,>«ognitively impaired,
economically or educationally disadvantaged persons, patients
of researchers, seriously ill persons) so that they are denied
opportunities to participate in research? ;
10. If the subjects are susceptible to pressures, are there
mechanisms to reduce the pressures or minimize their impact?
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study designs require retention strategies that ensure that adequate sample sizes are maintained
for meeting study objectives. It is recommended that researchers and IRBs evaluate the level of
burden in longitudinal studies and ensure that retention strategies are not likely to create
conditions of coercion or undue influence.
Some of the common strategies for maintaining
high retention rates in longitudinal studies are listed in
Text Box 5-4.
It is important that strategies that use payments to
encourage retention should be carefully scrutinized
against the possibility that they will result in undue
influence or diminish voluntary participation. Payments
that cover expenses and for time and burden at each visit
have to be reasonable, and researchers and IRBs should
consider whether the cumulative level of payments over
time or the use of escalating payments or final bonus
payments might present undue influence on decision-
making regarding participation. Participants have to feel
capable of withdrawing from participation at any time,
and escalating payments or completion bonuses can
impact decisions to withdraw. Withholding all payment until all study visits are completed or
making payment contingent on completing all activities is not an acceptable practice in most
longitudinal studies because it can diminish the capacity for voluntary participation. (See the
earlier discussion about payment issues in long-term studies in Section 5.2.3.)
People are more likely to continue active participation in longitudinal studies when they
believe that the research is important and that they are making a valuable contribution, are
receiving regular feedback, and are treated with courtesy and respect by researchers.
Observational human exposure studies sometimes involve substantial burdens of time and effort.
Over long times, this level of burden can reduce retention. It may be necessary to develop novel
methods that reduce participant time and effort or to focus the study design so that fewer study
procedures are implemented at any time point. Because the time needed to analyze samples,
verify results, and perform data analyses can take a long time, it may be difficult to provide
timely feedback to participants in measurement studies. Researchers might consider including
simple measures that can provide immediate and useful information of value to participants to
encourage continued participation. Effective use of these strategies will reduce the need for
higher payments to encourage retention.
5.7 Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk
Researchers and IRBs need to ensure that the procedures and materials used to recruit and
retain study participants in observational human exposure studies do not "undermine free and
informed consent by leading parents to expose their children to unacceptable risks." Payments in
observational studies should not be so high that they would cause an undue inducement for a
participant to use a product they would not normally use or to perform an activity that they
would not normally perform (see Section 5.2.3). Not only would this bias the study results but
may lead to higher than normal levels of exposure. Alternatively, the act of studying one set of
conditions or activities in an observational human exposure study could lead participants to
assume that those conditions or activities involve substantial risk. In response, they may
subsequently change their activities in ways that could lead to possibly higher (or lower) risks.
The potential for such unintentional outcomes is very hard for researchers to gauge but requires
researcher caution in how information and results are conveyed. However, if the informed
Text Box 5-4. Common strategies for
maintaining high retention rates in
longitudinal studies
• developing and maintaining a strong study
identity;
• building participant trust;
• communicating regularly with participants;
• providing feedback that is of use,to %
participants;
• maintaining confidentiality;
• incorporating active participant,tracking
mechanisms;
• maintaining reasonable levels of burden;
• providing periodic tokens of appreciation; and
• providing reasonable levels of payment or
other remuneration at each time point,
sometimes including escalating payments or
a higher final payment for completion of all
studyactivities..
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consent process is truly "an on-going, interactive dialogue . . . involving the disclosure and
exchange of relevant information," then such misunderstandings should be minimized.
5.8 References
AAP (American Academy of Pediatrics Committee on Environmental Health) (2003). Pediatric and Environmental
Health. (2nd Edition). Elk Grove Village, IL: American Academy of Pediatrics.
Ackerman TF (1989). An ethical framework for the practice of paying research subjects. IRB 11(4): 1-4.
CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection
of Human Subjects. U.S. Code of Federal Regulations. Available:
http://www.access.gpo.gOv/nara/cfr/waisidx_06/40cfr26_06.html [accessed 12 June 2007],
CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines
for Biomedical Research Involving Human Subjects. World Health Organization. Geneva. Switzerland. Available:
http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007],
Diekema DS (2005) "Payments for Participation of Children in Research." Chapter in: Kodish. E, Editor. Ethics and
Research with Children: A Case-Based Approach. New York, NY: Oxford University Press. 143-160.
Dickert N, Emanuel E, Grady C (2002). Paying research subjects: an analysis of current policies. Annals of Internal
Medicine 136(5):368-373.
Emanuel EJ (2004). Ending Concerns about Undue Inducement. Journal of Law, Medicine, and Ethics 32:100-105.
Emanuel EJ, WendlerD, Grady C (2000). What Makes Clinical Research Ethical'.' JAMA 20:2701-2711.
Erlen JA, Sauder RJ, Mellors MP (1999). Incentives in research: ethical issues. Orthopaedic Nursing 18(2):84-87.
European Parliament (2001). On the approximation of the laws, regulations, and administrative provisions of the
Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal
products for human use. Directive 2001/20/EC Article 4(d) of the European Parliament and of the Council of 4 April
2001.
Flory J, Emanuel E (2004). Interventions to Improve Research Participants' Understanding in Informed Consent for
Research: A Systematic Review . JAMA 292(13): 1593-1601.
Fry CL, Ritter A, Baldwin S. Bowcn KJ, Gardiner P, Holt T, Jenkinson R, Johnston J (2005). Paying research
participants: a study of current practices in Australia. Journal of Medical Ethics 31:542-547.
Grady C, Dickert N. Jawctz T, Gensler G, Emanuel E (2005). An analysis of US practices of paying research
participants. Cot^erhpprary Clinical Trials 26:365-375.
litis AS. De Vader S. Matsuo H (2006). Payments to children and adolescents enrolled in research: a pilot study.
Pediatrics 118(4): 1546-1552.
IOM (Institute of Medicine) (2004). Ethical Conduct of Clinical Research Involving Children. Marilyn J. Field and
Richard E. Behrman (eds). Washington, DC: The National Academies Press.
IOM (Institute of Medicine) (2002). Responsible Research: A Systems Approach to Protecting Research
Participants. Daniel D. Federman, Kathi E. Hanna, and Laura Lyman Rodriguez (eds). Washington, DC: The
National Academies Press.
Menikoff J (2005). Human Subject Testing of Babies, Bugs, and Bombast: A Look Behind the Crash-and-Burn of
the CHEERS Pesticide Study. Medical Research & Law Policy Report 4(14):586-512.
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NCS (National Children's Study) (2007) Research Plan, Volume 1, Version 1.1, June 20, 2007. Available:
www.nationalchildrensstudY.gov/research/research plan/upload/Research Plan Volume l.pdf [accessed 12
September 2007.].
NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for
the NIH Director from the Director's Council of Public Representatives (COPR). National Institutes of Health,
Director's Council of Public Representatives, January 14, 2005. Accessed via the internet at
http://copr.nih.gov/reports/public trust.asp (accessed June 2007).
NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
Housing-Related Health Hazards Involving Children. Committee on Ethical Issues in Housing-Related Health
Hazard Research Involving Children, Youth and Families, Bernard Lo and Mary Ellen O'Connell (cds). Board on
Children, Youth, and Families, Division of Behavioral and Social Sciences and Education and Inslilulc of Medicine.
Washington, DC: The National Academies Press. 216 pp. Available:
http://books.nap.edu/catalog.php?record_id=11450 [accessed 12 June 2007],
Paasche-Orlow MK, Taylor HA, Brancati FL (2003). Readability Standards for Informed-Consent Forms as
Compared with Actual Readability. N Engl J Med 348(8):721-6.
Russell ML, Moralejo DG, Burgess ED (2000). Paying research subjects: participants" perspectives. Journal of
Medical Ethics 26:126-130.
U.S. DHEW (U.S. Department of Health, Education, and Welfare (1979) The Belmont Report: Ethical Principles
and Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of
Human Subjects of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html
[accessed 12 June 2007],
U.S. FDA (U.S. Food and Drug Administration) (1998). Information Sheets: Guidance for Institutional Review
Boards and Clinical Investigators 1998 Update. U.S. Food and Drug Administration, Washington, DC. Available:
http://www.fda.gov/oc/ohrt/irbs/toc4.html [accessed May 20071.
U.S. HHS (U.S. Department of Health and Human Services) (1993). The Institutional Review Guidebook. Office for
Human Research Protections. Available: http://www.hhs.gov/olirp/irb/irb_guidebook.htm [accessed 12 June 2007],
VanderWalde A (2005). Undue inducement: the only objection to payment? The American Journal of Bioethics
5(5):25-27.
Weise KL, Smith ML, Maschkc KJ. Copcland L (2002). National practices regarding payment to research subjects
for participating in pediatric research. Pediatrics 110(3):577-582.
Wendler D, Rackoff JE. Emanuel EJ. Grady C (2002). The ethics of paying for children's participation in research.
The Journal ofPediatmc£%4\{2):\66-\l\.
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SECTION 6
Building and Maintaining Appropriate Community and
Stakeholder Relationships
Community engagement promotes active community involvement in the processes that
shape research strategies and the conduct of research studies. In developing this document,
NERL held an expert panel workshop to identify the content and organization of this document
(ERG, 2007). That panel of experts concluded that the need to engage the community in
observational research was based on the ethical principles of (1) respect for persons, which
manifests itself in both a respect for the individual and, through respect for the community, its
culture; (2) fairness, resulting in efforts to assure equity in resources, burden, and benefits; and
(3) beneficence, including "empowering the community to endure."
Involving the community in the research effort can improve the research both
scientifically and the ethically. In the document, Ethical Considerations for Research on
Housing-Related Health Hazards Involving Children, the joint NRC-IOM Committee found that
community involvement was a "guiding theme" of their findings (NRC & IOM, 2005). Because
the researchers were working in the homes and the communities of the participants, they faced
issues that were different from a clinical setting. They were challenged to think about the
fundamental ethical principles in the context of the research setting and about how those ethical
principles should be interpreted in that setting. "When researchers discuss a planned study with
community representatives, understand their concerns and needs, and respond to them, protocols
can be strengthened both scientifically and ethically" (p. xii, NRC & IOM, 2005). Just as was
described in section 5, where the informed consent process was described as needing to be "an
on-going, interactive dialogue between research staff and research participants involving the
disclosure and exchange of relevant information, discussion of that information, and assessment
of the individual's understanding of the discussion" (Recommendation 4.1, IOM, 2002), so, too,
the process of community involvement should be a process of effective two-way communication.
These NRC & IOM comments emphasize how critical effective, bidirectional communication is
to the scientific and ethical foundation of a research study in such a setting.
EPA has established a public involvement
policy to "improve the content of the Agency's
decisions and enhance the deliberative process"
(U.S. EPA, 2003). (See Text Box 6-1.) The policy
is focused largely on Agency decision-making
processes (e.g., rulemaking, permit issuance,
Superfund remediation, etc.), whereas observa-
tional exposure studies are research that is in-
tended to provide data to inform those decision-
making efforts. Nonetheless, the Agency policy
may be helpful in planning for community involvement in observational human exposure re-
search studies. The policy is intended to promote mutual trust and openness between EPA and
the public, to improve the quality of the Agency's actions, and to promote the public's involve-
ment in the Agency's mission of promoting human health and the environment. The policy iden-
tifies seven basic steps for effective public involvement and offers guidance for implementing
public involvement at EPA
Text Box 6-1. Seven Basic Steps
for Public Involvement at EPA
1. Plan and budget for public involvement activities
2. Identify the interested and affected public
3. Consider providing technical or financial assistance to
facilitate involvement
4. Provide information and outreach to the public
5. Conduct public consultation and involvement activities
6. Review and use input, and provide feedback to the
public
7. Evaluate public involvement activities
a
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6.1 Approaches to Community Involvement
Community involvement can take many forms. The forms of community involvement are
not mutually exclusive, and researchers may use several approaches for seeking community
involvement. The nature and extent of community involvement reasonably would depend on the
nature of the research itself. In Section 2, the authors discussed some reasons for involving the
community early in the research planning and scoping process and the benefits that community
involvement may bring to the research effort. "Community residents can be involved in the
research process as research staff, through community consultation and review, membership on
community advisory boards, and involvement in a community-based participatory research
process" if that is used (p. 83, NRC & IOM, 2005). In addition, IRBs may seek additional
community representation on the IRB panel.
One form of community involvement is to include qualified members of the community
on the research staff. Section 2 advocates community representatives as part of the research
team. Paid research staff members from the community could serve as valuable consultants for
protocol development and research design, including how to collect the data, how to recruit and
retain participants, and how to interpret and disseminate the results. Of course, researchers will
need to ensure that anyone hired has the requisite skills (p. 84, NRC & IOM, 2005).
A second approach to community involvement is to seek community consultation and
review. Researchers may periodically meet with community residents in a process of
"engagement, dialogue, and feedback" (Dula, 1994) to discuss research plans, research progress,
and results. The objective is to seek a dialogue with community residents. Effective
communication—open, honest, jargon free—will be an important factor in the successful use of
this approach.
CABs also have been used as an approach for getting the community involved in the
research effort. A CAB could be formed to advise the researchers about community issues and
concerns. The board can be sufficiently large to ensure a diversity of community views,
perspectives, and attitudes. Representatives from the board may be selected for participation on
the research team. In Section 5, the authors mentioned that such a board could function as an
oversight committee in case of any participant grievances.
Another potential approach to involve the community is to use a community-based
participatory research (CBPR) approach, wherein the community is actively involved in each
step of the research process, including the sharing of decision-making power and resources. This
will impact decisions about study design, study methods, dissemination of findings, and resulting
actions. "Under the principles of community-based participatory research, research must address
the concerns, needs, and priorities of the communities where it is conducted and lead to actions
and changes that benefit the community" (p. 86, NRC & IOM, 2005). Information about CBPR
approaches can be found at the HHS Web sites, www.ahrq. gov/clinic/epcsums/cbprsum.htm and
www.ahrq.gov/research/cbprrole.htm. Israel et al. (2005a) reviewed the results of CBPR efforts
at six Children's Centers co-funded by EPA and the National Institute of Environment Health
Sciences. They found that considerable commitment of resources and time are needed for the
approach to be successful, and the translation of research findings into interventions and policies
is of the utmost importance. Community partners played little role in defining the research topics
and data analysis, but were vital to disseminating the findings to the community. Corburn
describes a successful community participation in an EPA exposure assessment (Corburn, 2007).
He also explains how a shift of focus from risk assessment to exposure assessment may provide
an opportunity for community engagement to improve the technical assessment (Corburn, 2002).
One additional opportunity for community input may involve participation on an IRB.
IRBs are required by the Common Rule to have members who are sensitive to "community
attitudes" [40 CFR 26.107(a)], How they meet this obligation is totally at their discretion and
NERL researchers have no influence. There have been a number of recent articles in the
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literature about IRBs that have envisioned a need for more regulatory reform (Ledford, 2007).
Ideally, the IRB should take into account the views of the community. Quinn (2004) argues for
extending protections now reserved for individuals to groups (populations and communities)
through CABs. Her argument is that there are "ethical issues related to research with
communities that are distinctly different from the ethical issues related to research with
individuals." CAB members have to be educated on human subjects' protections, should
represent their communities honestly, and need to be willing to interact with researchers on
complex research issues.
Gilbert (2006) goes even further. He suggests supplementing or even replacing traditional
IRBs with an environmental health and community review boards (EHCRBs). He argues that
traditional IRBs are inadequate for the review of community-based research because they were
developed to address issues related to individuals involved in research projects, not communities.
He proposes EHCRBs that combine the fundamental and ethical concept of traditional IRBs with
an expanded ethical construct of dignity, veracity, sustainability, and justice, with an added
emphasis on community. He envisions that an EHCRB would function as an IRB with the
requirements and responsibilities for review for the protection of human subjects, plus the
additional role for review of community issues associated with the research project.
Gilbert's recommendation for EHCRBs is consistent with the recommendations of the
authors of the NRC & IOM report who recommended that "Institutional review boards that
review housing health hazards research involving children should ensure that those boards have
the necessary expertise to conduct a complete and adequate review, including expertise on
research involving children and community perspectives" (NRC & IOM, 2005).
Involving community representatives in the IRB process is challenging for IRBs,
however. One challenge could be the need to provide sufficient training to community members
about the IRB process and the regulations governing IRBs. This can be significant if members sit
on an IRB for a limited time to review specific community-based studies. In some cases, IRBs
may invite community members to participate in the IRB process as nonvoting members to
solicit the community perspective. This approach, which would be totally at the discretion of the
IRB, would reduce the burden on the community representative by not requiring extensive
training.
6.1.1 Issues in Community Involvement
There are a number of issues that need to be addressed in any efforts to ensure
community involvement. The expert panel that was convened to advise NERL about scientific
and ethical issues in observational human exposure studies discussed a number of challenges
(ERG, 2007). The topics that the expert panel identified as issues are discussed below.
6.1.1.1 Defining "Community."
Community refers to a group of people united by a shared attribute, and the attributes can
be wide-ranging, such as geography, culture, social characteristics, values, interests, traditions, or
experiences (ERG, 2007). Community can be defined broadly (as a system of interrelated groups
operating to meet the needs of its members) or more narrowly (as the population from which
study participants are selected). For observational field studies, the expert panel from the
workshop suggested the narrow definition. A narrow definition allows social and cultural factors
to be included but excludes government agencies, industry, and others who do not necessarily
represent the interests of the participants (ERG, 2007).
Central to the definition of a community is a sense of "who is included and who is
excluded from membership" (NRC & IOM, 2005). A person may be a member of a community
by choice, as with voluntary associations, or by virtue of their innate personal characteristics,
such as age, gender, race, or ethnicity (NRC & IOM, 2005). As a result, individuals may belong
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to multiple communities at any one time. When initiating community engagement efforts, one
should be aware of these complex associations in deciding which individuals to work with in the
targeted community.
Understanding and describing a community (CDC, 1997) involves exploring factors
related to
• people (including socioeconomics and demographics, health status, and cultural and ethnic
characteristics),
• location (geographic boundaries),
• commonalities (including shared values, interests, and motivating forces), and
• power relationships (including formal and informal lines of authority and influence,
stakeholder relationships, and resource flows).
It is important to distinguish between stakeholders and the community, but both should
be engaged at some point in the course of a study. Stakeholders include business, industry, and
various levels of government. A critical difference between the two is that the community has a
right to speak for its own interests, but stakeholders cannot speak for the community. Although
relationships with stakeholders can at times be confrontational, stakeholders often provide useful
information and expertise. When stakeholders and the community members overlap in particular
individuals, it is important to distinguish the role in which the individual is acting (ERG, 2007).
6.1.1.2 Identifying Who Represents the Community.
To sufficiently represent the community, an individual has to have not only the right to
speak for the community's interests (a right afforded by legitimate membership in the group) but
also should be able to articulate those interests on behalf of the community. Identifying those
who represent the community is not simply a matter of identifying the most vocal activists
because those individuals do not necessarily represent the interests of the entire community. In
fact, several individuals may be necessary to adequately represent the diversity of viewpoints
within a community; in such cases, a CAB may be appropriate (ERG, 2007). One of the
researcher's first steps should be asking the potential participants from the community who they
see as a legitimate representative—someone who can speak for them. Corburn cites an example
of a locale in Brooklyn, NY, that contained individuals with widely different backgrounds. It was
impossible to identify appropriate spokespeople, or even to define the nature of the community,
without talking with community members (Corburn, 2007).
The NRC and IOM Report (NRC & IOM, 2005) also discusses the issue of who can
represent the identified community. Some communities may have a formal governmental
structure and a recognized political authority (e.g., Native American tribes). Other communities
may have clearly identifiable leaders (e.g., religious communities), while still other communities
have no formal leadership structure at all. Whether there is a legitimate political authority or
some other hierarchal leadership structure, the goal is to identify those who best represent the
interests of the community with regard to the proposed research project, rather than selecting
those who are favorable to the research project. The NRC & IOM report cautions against the
ethically questionable practice of seeking out population spokespeople and research participants
whose positive response to a research plan can be predicted in advance and refers the reader to
an article on this topic by Juengst (2000). With multiple sources of leadership and authority in
many communities, careful consideration should be given to what aspect of the community a
particular person will represent and what efforts may be needed to ensure that the entire range of
views in a community are obtained. Researchers should consider reaching out to multiple
organizations such as churches, social service agencies, and tenant and other advocacy groups.
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6.1.1.3 Building Relationships and Trust.
A key first step in developing trust is to establish a relationship with the community
before the study. Trust must be built; it cannot be assumed. This relationship involves not only
listening to community input but actually taking it into consideration (ERG, 2007). A long
history of research with no direct benefits and no feedback of results to the community, however,
has contributed to a general mistrust of researchers by community members (Israel et al., 1998).
Moreover, the recurring abuse of trust in communities is a reality that researchers should be
aware of when attempting to build a long-term relationship (Minkler and Wallerstein, 2003). Past
ethical failures have created23 distrust among some communities and have produced great
challenges for current community organizers. Although it may seem self-evident, researchers
need to remember that ethical action is necessary for developing and maintaining the trust of
communities (CDC, 1997)
Developing trust is a difficult and time-consuming process. Israel et al. (2005b) suggest a
number of ways partners can gain each other's trust: First, partners can show respect by seriously
considering the ideas and opinions of others. Second, trustworthiness can be demonstrated by
following through with those things that each partner commits to. Third, partners have to respect
confidentiality. Fourth, they recommend attending to each other's interests and needs by
participating in activities beyond the specific work of the partnership.24 A history of prior
positive working relationships is also beneficial (Israel et al., 1998).
Trust cannot be separated from respect. Potential participants need to see researchers
fostering respect for community members and opinion leaders. For example, meeting with key
community leaders and groups in their surroundings helps tf) build trust for a true partnership.
Such meetings provide organizers of engagement activities with more information about the
community, its concerns, and factors that will facilitate and constrain participation. Once a
successful rapport is established, the meetings and exchanges with community members can
become an ongoing and substantive partnership (ERG, 2007).
One mechanism for helping to build trust may be a contract with the community. A
community contract outlines the roles and expectations of both the researcher and the
community. Living up to these agreements builds trust with all partners, and the establishment of
the agreement helps reduce misunderstandings. Contracts or memorandums of understanding
that outline the roles and expectations of the researcher and the community are discussed in both
Minkler and Wallerstein (2003) and Israel et al. (2005b). An example outlining expectations in a
partnership with tribal communities is presented in Appendix E of Minkler and Wallerstein
(2003), whereas an example discussing access to data and authorship issues is presented in
Appendix I of Israel et al. (2005b). An example of a memorandum of understanding between the
University of Michigan School of Public Health, Detroiters's Working for Environmental Justice
(DWEJ), the Detroit Hispanic Development Corporation (DHDC), and the Warren Conner
Development Coalition (WCDC) for a study investigating asthma is available at
http://depts.washington.edu/ccph/pdf files/MOUlO.pdf.
Work within communities involves a considerable investment of researchers' and
residents' time. It should be an ongoing, interactive exchange of information and ideas between
the researchers and the community members, where voices are both heard and honored. Trust is
fostered when all interested parties feel that they have influence, and that their input contributes
to the community effort. The collaborations should be inclusive of the entire community,
including those members with incompatible interests and perceptions. If participation, influence,
23 For a more complete discussion of overcoming suspicions, please see Perkins and Wandersman (1990).
24 For a more detailed description of each of the suggestions for enhancing trust, please see Chapter 3 of Israel et al.
(2005).
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and benefits are limited only to some of the partners, then distrust is likely, and the potential
benefits of community involvement may be lost. Being inclusive can create some organizing
challenges, but the benefits of effective community involvement "has the potential to lead to
greater understanding of community perspectives of the risk and benefits of research, improve
informed consent, increase study enrollment, enhance data validity and quality, and build trust
for research" (NRC & IOM, 2005).
6.1.1.4 Importance of Language.
Even when all partners and community members are speaking the same language, some
terms are not necessarily understood by all. Materials distributed to participants should be
reviewed by all partners to ensure that the language used will be understood by all participants.
Even among the partners, understanding each other's meanings is essential so that all partners
can move forward with a common understanding (Israel et al., 2005b).
Minkler and Wallerstein (2003) note that "research must be produced, interpreted, and
disseminated to community members in clear, useful, and respectful language." Researchers, and
especially researchers in a government agency, may have their own distinct lexicon. Researchers
should be careful to avoid acronyms, jargon, or technical terms that may obscure the meaning or
intimidate participants who are not familiar with the terms. Communicating in "plain language"
to "explain the research in an honest, straightforward way" will help build a strong relationship
with the community and the participants and also help enhance public trust (Recommendation
11, NIH, 2005).
6.1.1.5 Recognizing and Addressing Cultural Differences.
Building and maintaining appropriate community and stakeholder relationships requires
acknowledgment of the diversity within racial and ethnic groups. Different groups in the study
area may have different cultural norms and practices. The researchers should take these issues
into consideration as they work in the community. Community partners can help researchers
design the study to be attentive to the increasing heterogeneity of racial and ethnic groups
(Minkler and Wallerstein, 2003, Chapter 4) and to the different boundaries of privacy (crucial
when designing sampling strategies) of different groups (Israel et al., 2005b, Chapter 11). Vega
(1992) provides a thorough discussion of the theoretical and pragmatic implications of cultural
diversity for community research.
6.1.1.6 Honesty, Power Relationships, and Partnerships.
The NRC & IOM report (NRC & IOM, 2005) describes a relational paradigm that
acknowledges that research is part of a broader societal context, with the conduct of research
often mirroring a system in which power is unequally and perhaps unfairly distributed. The trust
and mutual commitment required from the researches and the community are subject to the
overall power relations in society.25 The expert panel report (ERG, 2007) emphasized that the
researchers had a variety of forms of power that needed to be understood and acted on ethically.
One form of power is resources, both funds and access to resources and decision-makers. Other
forms of power may be more subtle, including expertise, which can intimidate or limit a
participant's choices. Peer pressure, fear of intimidation, expectations of benefits from the
research, and power to stigmatize the community all, whether real or perceived, can influence the
relationship between the researcher and the community. Many forms of power may be tipped
toward the researcher, but the community often has power in the form of knowledge about the
25 A discussion of the evolution of theories on power relations, including the contribution of feminism, poststruc-
turalism, and postcolonialism, can be found in Minker and Wallerstein (2003, Chapter 2).
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community that can impact the quality of the research effort. An ethical balance of power can
lead to benefits for all partners (ERG, 2007).
In describing principles in Methods in Community-Based Participatory Research for
Health, Israel et al. (2005b) describe CBPR as facilitating "a collaborative, equitable partnership
in all phases of research, involving an empowering and power-sharing process that attends to
social inequalities." One way to address the inequities is to ensure that the roles and
responsibilities are mutually acceptable to all parties. Researchers involved in CBPR should
recognize and address the inequalities, thereby promoting trust, mutual respect, open
communication, information sharing, collaborative decision-making, and resource sharing.
6.1.1.7 Building a Lasting Infrastructure.
Researchers should be prepared to address early on those issues that will become
important once the research has been completed, such as publication and dissemination of
results. Infrastructure is anything that builds the capacity of the community by providing its
members with skills and resources. Infrastructure building ideally occurs throughout the project
and should be included in the overall plan (ERG, 2007).
When involving the community in the planning process, researchers need to be forthright
regarding funding limitations. The community needs to be made aware of the ephemeral nature
of funding, even if it results in apprehension toward involvement. Frankness is required to
cultivate the community's confidence and expertise over time. Because so much time and
investment is involved in building an appropriate relationship with the community, researchers
may wish to continue their relationship with the communit/even after the study has ended.
Researchers should remain accessible for technical support related to the subject of the research.
Helping community members identify new funding opportunities and assisting with the writing
of grant applications are two examples of potential continued relationships. Many private
sponsoring institutions already recognize the importance of enduring commitment and have used
a variety of approaches, often involving funding, to ensure that these relationships are able to
continue (ERG, 2007). The challenge will be for universities and Federal agencies to be able to
establish similar funding mechanisms.
The objective of capacity building is to involve members of the community in certain
roles (e.g., performing interventions), training them to perform some of the functions initially
performed by the research team. Certain research grants specifically support this type of training.
Training can be reciprocal, and allowing the community to train the researchers (for example, in
cultural sensitivity) not only fosters respect but also can lead to important new understanding.
Another important step is to formalize the relationship between the community and the
institution conducting or sponsoring the research, not just between the community and the
individual researcher. Institutional relationships can survive even if individual researchers leave.
Institutions may be reluctant to build enduring relationships with communities if they do not see
long-term financial value in this investment. Researchers may be able to get more support from
their institutions if they can document their successes (ERG, 2007).
6.2 Community Involvement and Observational Research
Observational exposure studies, like those conducted by NERL, likely would benefit
from community involvement. The form and extent of community involvement will vary,
depending on the scope and utility of the research effort. The nature of the community—the
population from which the participants are selected—often will vary considerably from one
study to the next, ranging from a small group involved in a pilot study to a randomized,
representative sample of the whole population. As a result, the nature of the community
involvement also will depend on the particulars of the study. The typical lack of direct benefit
from observational human exposure studies may mean that many of NERL's research efforts
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cannot meet all of the principles of CBPR. Nonetheless, community involvement, to the extent
applicable, should be included in all of NERL's exposure research efforts. As the NRC & IOM
Committee observes (p. 98, NRC & IOM, 2005):
Community involvement, though time and resource intensive, is a necessary and
useful component of. . . research with the potential to enhance trust and increase
the relevance of research to affected communities. Thus, attention to the issues
raised by the community and consideration of the most appropriate method of
community involvement for a given research project is warranted.
NERL researchers also should consider the recommendations set forth in the NRC &
IOM report (Recommendation 5.1, p. 98, NRC & IOM, 2005) as they develop their research
plans and protocol.
Researchers . . . should describe in their protocols and IRB submissions how they
have involved and will continue to involve the affected community in the research
project, justify the lack of such involvement, and report how they have responded
to any community concerns.
6.3 Identifying and Interacting with Other Stakeholders
Stakeholders can provide useful information and perspective on exposure studies.
Stakeholders may include business, industry, and local or state governments or agencies with
jurisdiction over the community. Even though they are not able to speak for the community, they
may have knowledge of impacts and ideas about how to interpret and use the results. Such
knowledge may prove very helpful as part of the research planning and scoping (ERG, 2007).
Including a variety of stakeholders in the process provides insight that comes from reconciling
the disparate perspectives of different stakeholders. The concept of "stakeholder" has been
discussed in management literature since the 1980s. Mitchell et al. (1997) have developed an
approach for identifying the relevant stakeholders through an assessment of their power,
legitimacy, and urgency. Such an approach may be useful for identifying stakeholders to be
involved in the research studies. In describing CBPR, Israel et al. (2005b) discuss the need to
examine the advantages and disadvantages of extending membership beyond the "community of
identity" at the outset. For example, they discus the relative merits of including representatives of
the agricultural industry in a study of farmworkers because of industry's possible role in policy
change and weigh their inclusion against the concerns that the true voice of the farmworkers may
not be heard under such conditions. They also describe a possible solution of creating separate
partnership groups. O'Fallon and Dearry (2002) explain the benefits of including diverse
stakeholders for the dissemination of results.
6.4 References
CDC (Centers for Disease Control and Prevention) (1997). Principles of Community Engagement. ATSDR
Committee on Community Engagement. Available: http://www.cdc.gov/phppo/pce/ [Accessed Octo 2007],
Corburn J (2007). Community knowledge in environmental health science: co-producing policy expertise. Environ
Sci Policy 10(2): 150-161.
Corburn J (2002). Environmental justice, local knowledge, and risk: the discourse of a community-based cumulative
exposure assessment. Environ Mngt 29(4):451-466.
Dula A (1994). African American suspicion of the healthcare system is justified: What can we do about it?
Cambridge Quarterly of Healthcare Ethics 3(3):347-357.
ERG (Eastern Research Group) (2007). Report on the Workshop to Discuss State-of-the-Science Approaches for
Observational Exposure Measurement Studies. Final Report: January 25, 2007.
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1 Gilbert SG (2006). Supplementing the traditional institutional review board with an environmental health and
2 community review board. Environ Health Perspect 114(10): 1626-9.
3 Green LW, Mercer SL (2001). Can public health researchers and agencies reconcile the push from funding bodies
4 and the pull from communities? Am J Pub Health 91(12): 1926-1929.
5 IOM (Institute of Medicine) (2004). Ethical Conduct of Clinical Research Involving Children. Marilyn J. Field and
6 Richard E. Behrman (eds). Washington, DC: The National Academies Press.
7
8 Israel B A, Parker EA, Rowe Z, Salvatore A, Minkler M, Lopez J, Butz A, Mosley A, Coates L, Lambert G, Potito
9 PA, Brenner B, Rivera M, Romero H, Thompson B, Coronado G, Halstead S (2005a). Community-based
10 participatory research: lessons learned from the Centers for Children's Environmental Health and Disease Prevention
11 Research. Environ Health Perspect 113(10): 1463-71.
12 Israel BA, Eng E, Schulz AJ, Parker EA (eds) (2005b). Methods in Community-Based Participatory Research for
13 Health. San Francisco, CA: Jossey-Bass.
14 Israel BA, Schulz AJ, Parker EA, Becker AB (1998). Review of community-based research: assessing partnership
15 approaches to improve public health. Annu Rev Public Health 19:173-202.
16 Juengst ET (2000). Commentary: What "community review" can and cannot do. J Law Med Ethics 28(l):52-54.
17 Ledford H (2007). Trial and Error. Nature (448):530-532.
18 Menikoff J (2005). Human Subject Testing of Babies, Bugs, and Bombast: A Look Behind the Crash-and-Burn of
19 the CHEERS Pesticide Study. Medical Research & Law Policy Report 4( 14):586-512.
20
21 Minkler M, Wallerstein N (eds) (2003). Community-Based Participatory Research for Health. San Francisco, CA:
22 Jossey-Bass.
23 Mitchell RK, Agle BR, Wood DJ (1997). Toward a theory of stakeholder identification and salience: defining the
24 principle of who and what really counts. Academy of Management Review 22(4):853-886.
25 NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for
26 the NIH Director from the Director's Council of Public Representatives (COPR). National Institutes of Health,
27 Director's Council of Public Representatives. January 14, 2005. Available:
28 http://copr.nih.gov/reports/public trust.asp |accessed June 2007],
29
30 NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
31 Housing-Related Health Hazards Lnvolving Children. Committee on Ethical Issues in Housing-Related Health
32 Hazard Research Involving Children, Youth and Families, Bernard Lo and Mary Ellen O'Connell (eds). Board on
33 Children, Youth, and Families. Division of Behavioral and Social Sciences and Education and Institute of Medicine.
34 Washington. DC: The National Academies Press. 216 pp. Available:
35 http://books.nap.cdu/catalog.php?record_id=11450 [accessed 12 June 2007],
36 O'Fallon LR. Dcarrv A (2002). Community-based participatory research as a tool to advance environmental health
37 sciehc€^mviron Health Perspect 110 Suppl 2:155-9.
38 Perkins DD. Wandersman A (1990). You'll have to work to overcome our suspicions: The benefits and pitfalls of
39 research with community organizations. Social Policy 21(l):32-42.
40 Quinn SC (2004). Ethics in public health research: protecting human subjects: the role of community advisory
41 boards. Am J Public Health 94(6):918-22.
42 U.S. EPA (2003). Public Involvement Policy of the U.S. Environmental Protection Agency. EPA 233-B-03-022.
43 (Available at http://www.epa.gov/publicinvolvement/pdf/policv2003.pdf [Accessed Sep 26, 2007].)
44 Vega WA (1992). Theoretical and pragmatic implications of cultural diversity for community research. Am J
45 Commun Psychol 20:375-91
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6.4.1 Additional Information Resources
"Turning Point: Collaborating for a New Century in Public Health," supported by the W.K. Kellogg and Robert
Wood Johnson Foundations, see http://www.naccho.org/topics/infrastructure/TurningPoint.cfm [Specifically
"Fourteen Policy Principles for Advancing Collaborative Activity Among and Between Tribal Communities and
Surrounding Jurisdictions." http://archive.naccho.org/documents/TP-policy-principles.pdf].
Preventing Chronic Disease [online serial] available at http://www.cdc.gov/pcd/.
Blumenthal DS (2006). "A community coalition board creates a set of values for community-based research." Prev
Chronic Dis 3(1): 1-7. http://www.cdc.gOv/pcd/issues/2006/jan/pdf/05_0068.pdf.
Veazie MA, Teufel-Shone NI, Silverman G, Connolly A, Warne S, King B, Lebowitz MD, Meister JS (2001).
Building community capacity in public health: The role of action-oriented partnerships. J Public Health Manag
Pract 7(2):21-32.
University of Kansas Community Tool Box, see http://ctb.ku.edu/tools/en/tools_toc.htm.
University of Washington Community-Campus Partners for Health, see
http://depts.washington.edu/ccph/index.html.
U.S. Food and Drug Administration (FDA) Emergency Research Rules, see 21 CFR Section 50.24.
Coleman CH, Menikoff JA, Goldner JA, et al. The Ethics and Regulation of Research with Human Subjects.
Newark: Matthew Bender Co., 2005:3-50.
U.S. Environmental Protection Agency, Superfund Program "Community Involvement Handbook" (particularly
chapters 1 through 3), see http://www.epa.gov/superfund/lools/cag/ci_handbook.pdf
U.S. EPA (Environmental Protection Agency). (1999) Risk Assessment Guidance for Superfund: Volume I - Hu-
man Health Evaluation Manual. Supplement to Part A. Community Involvement in Superfund Risk Assessments.
EPA/540/R-98/042, March.
U.S. EPA (Environmental Protection Agcnc\ 2000b El Superfund Ho Dia. La Estimacion de Reisgos: Como Lograr
La participaton del la Communidad. Que cs las Estimacion del Riesgo para la Salud Humana? OSWER Directive
No. 9200.2-26K. Enero (fact sheet).
U.S. EPA (Environmental Protection Agency). (2001a) Early and meaningful community involvement. Office of
Solid Waste and Emergency Response. Washington, DC. OSWER Directive No. 9230.0-99, October 12.
U.S. EPA (Environmental Protection Agency). (2001b) Improved Science-Based Environmental Stakeholder Proc-
esses: A Commentary bv the EPA Science Advisory Board. EPA-SAB-EC-COM-01-006. EPA Science Advisory
Board. Washington. DC. http://www.epa.gov//sab/pdf/eccmO 1006.pdf
U.S. EPA (Environmental Protection Agency). (2003a). Framework for cumulative risk assessment. Washington,
DC: United States Environmental Protection Agency. Available online at
http://crpub2.cpa.gov/ncea/cfm/recordisplav.cfm?deid=54944.
U.S. EPA (Environmental Protection Agency). (2003b) Framework for children's risk assessment. Washington, DC.
Available from: http://clbub2.epa. gov/ncea/cfm/recordisplav.cfm?deid=22521.
U.S. EPA (Environmental Protection Agency). (2003c) Public involvement policy of the U.S. Environmental Pro-
tection Agency. May 2003. U. S. EPA, EPA-233-B-03-002. Available online at
www.epa.gov/policv2003/policv20Q3.pdf
U.S. EPA (Environmental Protection Agency). (2003d) A Framework for a computational toxicology research pro-
gram. Washington, DC:
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1 U.S. EPA (Environmental Protection Agency ). (2004) National Environmental Justice Committee (NEJAC) Ensur-
2 ing Risk Reduction in Communities with Multiple Stressors: Environmental Justice and Cumulative Risks/Impacts.
3 http://www.epa.gov/compliance/resources/publications/ei/neiac/neiac-cum-risk-rpt-122104.pdf
4
5 U.S. EPA (Environmental Protection Agency). (2005c) Guidance on selecting age groups for monitoring and assess-
6 ing childhood exposures to environmental contaminants. Risk Assessment Forum, Office of Research and Develop-
7 ment, Washington, D.C. EPA/630/P-03/003F. Available online at
8 http://cfpub.epa.gov/ncea/cfm/recordisplav.cfm?deid=146583
9
10 U.S. EPA (Environmental Protection Agency). (2006a) (External Review Draft) Considerations for Developing Al-
11 ternative Health Risk Assessment Approaches for Addressing Multiple Chemicals, Exposures and Effects. Washing-
12 ton, DC.
13
14 U.S. EPA (Environmental Protection Agency). (2006b) Paper on tribal issues related to tribal traditional lifev\a> s.
15 risk assessment, and health and well being: Documenting what we've heard. The National EPA-Tribal Science
16 Council.
17
18 U.S. EPA (Environmental Protection Agency). (2006c) EPA's homepage on community involvement. Available
19 online at http://www.epa.gov/publicinvolvement/policv2003/index.htm.
20
21 6.4.2 U.S. EPA, Office of Environmental Justice resources:
22 "Environmental Justice Strategy," see http://ww.epa.gov/compliancc/resources/policies/ej/ej_strategy_1995.pdf.
23 "Environmental Justice: Guidance under NEPA" (particularly pg 7-17). see
24 http://www.epa.gov/compliance/resources/policies/ej/ej_guidancc_nepa_ceql297.pdf.
25 "Enforcement Assessment Tool" for identifying populations with respect to minority, vulnerability, and/or economic
26 factors, see http://www.epa.gov/complicance/resourccs/policics/cj/ej-seat.html.
27 "Toolkit for Assessing Potential Allegations of Environmental Injustice" (Section 3.3) for indicators of
28 subpopulations, see http://www.epa.gov/complicancc/rcsources/policies/ej/ej-toolkit.pdf.
29 "Environmental Justice Collaborative Problem-Solving Cooperative Agreement Factsheet" for key elements for
30 community and stakeholder involvement, sec
31 http://www.ep.gov/compliancc/rcsources/publications/ej/factsheets/fact-shet-ejcps-grants-6-13-03.pdf.
32 National Environmental Justice Advisory Council's (NEJAC's) "Model for Public Participation" for desired
33 participants, core values, and guiding principles, see
34 http://www.epa.gov/compliance/resources/publications/ej/nejac/model-public-part-plan.pdf.
3 5 "Guide on Consultation and Collaboration with Indian Tribal Governments" (Chapter 4) for guidance on public
36 participation, see http://www.lm.doe.gov/envJustice/pdf/ips_consultation_guide.pdf.
37 "Environmental Justice and Community-Based Health Model Discussion" (Section l.A) for NEJAC's summary of
38 data gathering efforts and the need for exposure data, see
39 hllp://www.cpagov/compliance/resources/publications/ej/nejac/community-based-health-recom-report.pdf.
40 "Environmental Justice and Federal Facilities" for recommendations to improve agency-community relationships
41 and cultural sensitivity, see
42 http://www.epa.gov/compliance/resources/publications/ej/nejac/ffwg-final-rpt-102504.pdf.
43 "Meaningful Involvement and Fair Treatment by Tribal Environmental Regulatory Programs" for definitions of
44 "meaningful involvement" and "fair treatment" and descriptions of tribal views of appropriate public participation
45 and due process, see
46 http://www.epa.gov/compliance/resources/publications/ej/nejac/ips-final-report.pdf.
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"Future Mechanisms to Improve Stakeholder Involvement" for recommendations to improve stakeholder
involvement in environmental justice-related processes, see
http://www.epa.gov/compliance/resources/publications/ei/neiac/stakeholder-involv-9-27-06.pdf.
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SECTION 7
Designing and Implementing Strategies for
Effective Communication
Successful implementation of observational human exposure studies requires effective
communications between the researchers, study participants, community representatives,
community members, and many other stakeholders, including the public. The previous two
sections established the need for communications that are "on-going, interactive dialogue . . .
involving the disclosure and exchange of relevant information, discussion of that information,
and assessment of the individual's understanding of the discussion" (Recommendation 4.1, IOM,
2002). NIH advocates "plain language" that explains the research "in an honest, straightforward
way" (Recommendation 11, NIH, 2005). Indeed, strong relationships can be built with
participants, the community, and stakeholders only if there are effective communications
between the researchers and the community. The previous section illustrates, also, that effective
communication is bidirectional: it involves listening as well as "speaking." The ethical value of
respect for persons, including respect for one another's autonomy and welfare, demands that
researchers, participants, community members, and stakeholders strive to establish effective
communications and to foster a relationship of trust and respect. The researchers should make a
commitment to effective communications and make the appropriate investment of time and
resources to ensure that the communications are at an appropriate level and are truly effective.
Communications have to be considered to be intrinsic to the ethical bases for the study.
With the ethical basis for effective, bidirectional communication assumed as a given, this
section discusses a number of tools that researchers may find useful in developing effective
communications. The focus in this section is primarily from the perspective of "getting the word
out," because that is the aspect of communication most under the control of the researchers.
Nonetheless, effective communications will be bidirectional and involve effective listening also.
Researchers should keep that in mind as they address issues related to research communications.
7.1 Communication Strategy and Implementation
Plan
Fundamental to achieving effective
communications are a communications strategy and
implementation plan. The plan will describe who will
be involved in the communications, what
communications are required, and how the
communications will be performed. The
communication strategy and implementation plan
should be developed early in the planning stages of a
study. The communication plan, however, needs to be
dynamic, with revisions and updates occurring
throughout the study and in collaboration with the
community and stakeholders. Text Box 7-1 lists some
elements that should be included in a communication
plan. The communication strategy needs to be
developed based on the goals of the study and an
understanding of the background, education,
Text Box 7-1. Elements in a Communication
Plan
• -Background information description (overview) of
the study, relevant historical background
information, statement of communication needs,
and identification of communication opportunities
and issues
• -Purpose and goals or the communication strategy
• -Individuals and groups involved in the
communications list, plus relevant demographics
and other information to profile the groups
• -Strategy and approach for achieving the goals,
including a statement of the primary message to
be conveyed and descriptions of the
communication channels
• -Activities and materials to achieve the goals
specific elements of the plan to be performed
• -Timetable
• -Roles and responsibilities,
• -Resources needed (budget)
• -Means of evaluation measures of effectiveness
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attitudes, and opinions of the stakeholders and the community that will be involved in the many
different aspects of the study from the initial conceptualization to the final reporting of the study
results. Careful planning is required to develop a communication plan that will be effective. The
research team has to invest the time and resources necessary to develop and implement the plan.
They also should recognize that the communication plan is an essential document for conducting
the study, as necessary as the study design, human subjects research protocol, or QAPP. The
observational study, if properly justified as described earlier, provides a social and scientific
value and brings benefit to society (and perhaps the participants); it should be a program that the
researchers want to discuss and explore with the public. The communication plan and strategy
provide the researchers with an opportunity to describe the merit of their work. They are not
simply a way to "avoid problems" with stakeholders or the media nor only a plan for reacting to
"negative" communications.
Researchers may also find it helpful to seek
guidance on how to communicate more effectively,
especially since that is not a routine part of their training or
experience. They may consult and learn from
communications specialists in their organization. In
addition, a wide variety of resources are available. For
example, the Federal Communicators Network (FCN)
(www.fcn.gov) has prepared a "Communicators Guide"
that offers advice on how to communicate—in plain
language, in easily digestible "chunks," and in a form that
will be used. They emphasize that "good communication is
difficult because it requires a lot of effort, time, and
patience" (FCN, 2001). Some tips from the guide to help
federal communicators get their point across are listed in
Text Box 7-2.
Text Box 7-2. Tips for Getting Your
Point Across
• Be prepared.
• Be confident. /
• Stay focused on your conversation and your
listener. %
• Maintain eye contact with your listeners.
• Make sure your listeners are following you by
asking them for questions or feedback.
• Don't lose your temper or get over-emotional.
• Speak slowly and calmly; don't raise your
voice.
• Speak clearly and concisely.
• Get to the point; don't ramble.
• Be kind, compassionate, and empathetic.
• Be honest. Don't play games.
• Be assertive, but tactful
7.2 Individuals and Groups Involved in the Communications
An effective communication plan will identify and
involve all of the individuals and relevant groups that
should be included in the communications efforts. When
conducting observational studies, this list may be quite
long. Although researchers may desire to limit the number
of individuals and groups involved to keep the effort as
simple and focused as possible, they need to ensure that all
potential stakeholders are identified. The communication
plan should identify all of the stakeholders involved in a
study, their roles and responsibilities in the study, how
communications will be developed with each group, and
the timing of the communications. It is likely that most
studies will involve the individuals, community groups and
other stakeholders shown in Text Box 7-3.
The study participants are a key group involved in
communications about a study. The communications
approaches and materials are discussed in the following
subsections and in other parts of this document. Similarly,
it is generally not difficult to identify the third parties associated with the study participants.
Research teams should ensure that the communication strategy addresses third-party
communication issues also.
Text Box 7-3. Individuals and Groups
Involved in Communications
•Principal investigator—the researcher with
ultimate responsibility for the study
•Research team
•Study participants
•Third parties associated with study
participants (e.g., spouse, children,
landlords)
•Community representatives
•Community members
•Governments (local, State, Federal)
•Study institution management
•Study sponsors or funding organization
•Organizations with interest in the
participants, the community, or the research
question
•Stakeholders that may be impacted by the
results of the study
•The scientific community
•Media
•The general public
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As discussed in Section 6, it is critical that the relevant community representatives are
identified early in the scoping and planning phase of the study. It is important that researchers
understand and appreciate the characteristics and composition of the community that may
become participants in the planned study. If possible, researchers should identify other research
organizations who have worked in the community and attempt to gather information from them
on the nature of the community and on who represents the community. Understanding how the
community defines itself or thinks of itself is critical to establishing effective communications.
Identification of all the other relevant stakeholders groups may be more difficult. There
may be many organizations who consider themselves as stakeholders that represent the interests
of the community, the participants, or the research problem. For example, there are many
nonprofit organizations that advocate for the protection of children's health. When conducting an
observational study involving children, the research team should identify those groups that could
have an interest in the study. They need to be identified in the communication plan, and an
approach needs to be developed for communicating with them about the study. There are many
sources of information on potentially interested stakeholder groups. This information can be
obtained from the research team based on similar studies, the participants, the community
representatives, sponsoring organizations, and "umbrella" organizations for various advocacy
groups. The Internet has made identification of the various stakehol der groups easier and is a
source of information on goals of the groups and contact information.
Approaches for communications with these and other groups on the list are discussed
further in the following subsections.
7.3 Communications Timetables—When To Communicate
Communications begin with the initial conceptualization of the study and continue
through the reporting of the study results and beyond. Even after a study has ended, follow-up
communications may continue with the study participants, the community, the scientific
community, and the public. It is beyond the scope of this document to lay out timetables for
communications in observational studies because timing will differ with each study. The
following discussion highlights a few of the issues associated with the timing of communications
to ensure that they are effective. This section also does not discuss communications among the
research team, research organization, or study sponsors.
Researchers should begin the dialogue with the community as soon as possible during
study conceptualization and planning. Once the community in which the study will be performed
is identified, community representatives should be identified and contacted to discuss the
potential study and to get input on how the study may be designed. As discussed in Section 2, the
observational studies discussed in this document are generally not CBPR. But, although the
study objectives or hypotheses are defined, and the general approach for a study has been
developed, the community still can provide valuable input about their environmental of public
health concerns. Again, as discussed in Section 2, the planning for the study should be flexible
enough to incorporate community concerns where feasible. Even if the observational human
exposure research study is not be able to address all of the community's concerns, the value,
merit, and benefits from the study need to be communicated. An important component of the
communications strategy involves educating the community on the research questions and the
study, as described below. Communications with the community representatives will continue
throughout the study.
Press releases that provide information about upcoming observational studies may prove
to be important tools for engaging the communities in which studies will be performed and for
identifying additional stakeholder groups. Early in the study, researchers should develop press
releases and should work with community leaders and community members to make the
community at large and the general public aware of the upcoming study. These press releases
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will serve multiple purposes. They make community leaders who have not already been
identified by the researchers as stakeholders aware of the study. They provide publicity that will
inform community members about potential contacts by the research team (e.g., in a random
sample design). They provide publicity to public interest and advocacy groups who may feel that
they are stakeholders who should be involved in the study. Press releases also provide the
transparency for the study and the research team that is essential for building trust.
Observational studies also should be announced to stakeholders and the public (via the
media, community interactions, or other means) well in advance of study implementation. Large
grants expected to have significant impact in communities often are announced by EPA at the
research institution receiving the grant and in press releases to the local media. These studies,
therefore, are publicized very early in the study. Cooperative agreements, which are another
mechanism by which the government funds some research projects, are announced in the same
way. Cooperative agreements and observational studies performed by EPA researchers receive
additional public notice when they are reviewed by the Office of Management and Budget
(OMB) under the Paperwork Reduction Act. All studies involving collection of survey
information from more than nine people are reviewed by OMB. This involves submission of an
Information Collection Request (ICR) to OMB, announcement of the ICR in the Federal
Register, and an opportunity for public comment. A docket is established specifically to facilitate
public comment. This process results in widespread publication of upcoming government
research studies through scrutiny by concerned stakeholder groups who routinely review the
announcements in the Federal Register.
The process for announcing EPA-sponsored observational studies targets attempts to
reach a broad range of people and groups who may have interests in specific research topics. The
EPA Office of Public Affairs also maintains extensive lists of special interest groups. News
releases are directed to these groups on topics of interest. Communication plans should contain
early notification of the special interest groups to ensure transparency of communications.
To maintain transparency, the research team needs to maintain communication with the
participants, community, and stakeholder throughout the study. This can be aided by providing
project progress reports and interim results. In observational studies with repeated measurements
over seasons or years, meeting with participants regularly provides a mechanism for
communication and for improving retention. However, the researcher should advise the
participants on the implications of such meetings on privacy and confidentiality issues.
Community meetings also are effective for maintaining communications throughout a study.
They provide the opportunity to provide information to community representatives and to obtain
feedback. They also provide opportunities for news releases to the media to maintain continued
interest in the study.
7.4 Communicating at Different Levels
The diversity of interested people and groups often means that communications materials
should be developed at different levels of scientific literacy. In any case, the materials should all
be written in "plain language" that is honest and straightforward. Therefore, it is critical that
communications are at the appropriate level and that materials are written at a reading level that
is appropriate to the audience. For the nonscientist, many IRBs and other groups target materials
to be used with participants and communities at a reading level no higher than the 8l grade to
improve the likelihood of comprehension. In some communities, however, other factors, like
primary languages other than English, educational disadvantages, etc., may require
communications materials to be written in alternate languages and at different reading levels.
The issue is comprehension, as was discussed in Section 5.1.2. Researchers may find testing the
communications tools with focus groups or community representatives to be helpful. In addition,
researchers should recognize that in this information age, dissemination of informational
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materials may be rapid and widespread. Therefore, even informational documents intended for
scientific peers should probably include summary information in an executive summary or
preface that a lay reader can understand.
7.5 Communications Materials
Researchers need to communicate clearly with the many groups listed above in Section
7.2 to gain support for their research from the community, to engage participants in the study (for
both recruitment and retention), to gain support from stakeholders, and to inform the public. To
achieve the multiple purposes of communications during a research study and to communicate
with many diverse groups, a variety of communications materials may need to be developed.
Different materials have different purposes and different types of information to be
communicated. Because of diversity in interested individuals and groups with respect to
education, cultures, information needs, etc., the format and content of communication materials
likely will need to be diverse. Text Box 7-4 list activities and materials that may be helpful in
facilitating communications.
By definition, communication is an exchange of
information. This has to be the primary goal of
communication activities. The accuracy and completeness
of the information transferred is important. There are
many different ways to communicate, the effectiveness of
which varies substantially. The way in which the
information is conveyed is as important as the information
itself. Effective communication should promote trust and
credibility. Peters et al. (1997) found that three
determinants, (1) knowledge and expertise; (2) openness
and honesty; and (3) concern and care, were important
factors determining perceptions of trust and credibility.
Therefore, the approach to communication in
observational studies should consider these factors, and
communication materials should be developed with these
factors in mind.
When developing communication materials, the
researcher should consider the needs of the reader,
listener, or viewer with respect to content, scope, style,
and the level at which the materials are written. There are many sources of information on design
of informational materials, such as flyers or brochures. For example, Alderson (1995) provides
an example of the recommended content and style for information leaflets (that may also be
flyers or brochures) for pediatric medical research. She suggests that leaflets be provided to
parents of children who will be study participants that can be read to the children. She
recommends that these be provided at the time that the parent is being informed of the study,
prior to requesting the informed consent. The content of the leaflet would include the following
topics.
• Nature and purpose of the research
• Anticipated benefits of the research
• Risks, harms, costs, and inconvenience to the participant
• Assurance that the participant can freely refuse to participate in or withdraw from the study
• Details about remuneration
• Names of the project sponsors and the researchers
• Contact information for the researchers
• Respect for privacy and confidentiality
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Text Box 7-4. Potential Activities /
Materials that May Be Useful in a
I Communication Plan
• Direct mailings
> Presentations
|t:-Fpgus groups
I • Flyers
I • Brochures
I • Web sites
I • Newsletters
I • Press releases
* • Interviews
I • Desk statements (government)
I • Questions and answers Q&As
II • Talking points
5 • Abstracts
; • Study reports
• Study participant meetings
• Community meetings
• Stakeholder meetings
• Technical presentations
• Scientific meeting presentations
• Peer-reviewed scientific journal manuscripts
• Final reports describing the total research
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Leaflets and brochures that contain this information provide a tool for communication
with study participants. However, these materials need to be written carefully using everyday
terms that the average nonresearcher can understand. The brochure should be written in a
friendly style that conveys the intent of the researcher to engage the reader as a collaborator on
the study, not as a study "subject," who will be told to do a series of tasks as a requirement for
participation in the study.
These same leaflets and brochures can be used to inform other groups that may be either
involved or interested in the study, such as community representatives, stakeholder
organizations, the media, and the general public. The researcher should ensure that any brochure
developed for the study includes accurate and complete information that is less likely to be
misinterpreted by anyone who might pick up the brochure. Brochures and flyers that are used to
announce a study or are used as recruiting tools should be carefully written in plain language to
ensure that there is not a perception of activities that are unethical. For example, if flyers
announcing a study state that study participants will be compensated, the flyer needs to ensure
that the compensation is not the focus of the flyer, and that the remuneration does not appear to
be excessive and coercive (see Section 5.2). Flyers announcing a study generally do not include
the dollar amounts of remuneration. Researchers may use flyers to announce a study and a call
for participants, and then provide more detailed brochures to give to people after they indicate an
interest in participating. The purpose of the brochure is generally to provide more information
about the study so that the potential participant can make an informed decision as to whether or
not to participate. If the brochure includes a detailed description of remuneration for
participation, sufficient information needs to be included to justify the amount of remuneration
offered. If the information is inadequate, there may be a perception that the remuneration is
coercive.
Researchers need to have similar concerns about all of the communication materials that
are developed, regardless of the type of material, whether it is a direct mailing, a Web site, a
news release, or a set of Q&As used to respond to media or stakeholder inquiries. In developing
the communication materials, the research staff should seek the assistance, advice, and input of
people in their organization with experience in developing such materials. With all of these
materials, the researchers should be concerned with how the materials may be misinterpreted,
and whether there may be a perception that some element of the study would not meet the
highest ethical standards. In this age of rapid communications and widespread distribution of
information, if there is the slightest doubt about either of these questions, the communication
materials likely will be inadequate.
Because of rapid and widespread distribution of information via the internet,
communications have become more challenging because communications materials will be seen
by a wider audience than just the study participant and the community in which they live.
Communication materials should be prepared and available to inform the many stakeholders who
may be interested in observational human exposure studies. Because there can be disagreement
about the relative importance of different ethical values or about how to implement specific
ethical standards, there are bound to be questions raised about various study elements. As
described in other sections of this document, there may be controversy about many elements. For
example, remuneration for participants is one issue that still is being debated in the peer
community. As discussed in an earlier section, researchers should involve the community in
developing a remuneration approach and should ensure that communication materials adequately
explain that approach. Researchers also should anticipate questions on this element of the study.
Recognizing the importance of effective communication materials and their potentially
widespread dissemination, researchers need to assure their accuracy and effectiveness.
Researchers should seek input both internally in their organization and externally to ensure that
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the materials are effective. External input may be solicited from community representatives and
stakeholders interested in the research problem or the ethics of the research.
Research study Web sites are very useful for communicating information about
observational human exposure studies. Web sites should be developed early in the study to
disseminate information to stakeholders and the community. Additionally, the sites can be set up
with participant-only pages to provide more detailed information to study participants, including
information on study protocols that require participant assistance (e.g., protocols for collecting
urine samples, time/activity log entries).
The plan for disseminating information from the study should be developed in the early
design phases of the study and should be included in the study design document. Sufficient
resources, both time and funding, need to be budgeted for this activity.
7.6 Educating the Participants and Communities
Effective communications require that all parties, researchers and participants alike,
involved in the communication understand the content and context of the information being
exchanged. "When researchers discuss a planned study with community representatives,
understand their concerns and needs, and respond to them, protocols can be strengthened both
scientifically and ethically" (p. xii, NRC & IOM, 2005). Comprehension is one of the key pillars
of informed consent and it means that participants understand the key elements of the research.
The most effective way to improve comprehension is by talking one-on-one with study
participants.
To accomplish that, the researchers need to make a commitment to communicating with
and educating both the study participants and the community. This can require a substantial
investment of time and resources, but it is critical to the success of the study.
Educating the participants of the study will have many benefits. The more educated the
participant is about the purpose of the study and the activities to be performed during the study,
the more likely the participant will be to develop a beneficial researcher-participant relationship.
By taking the time to educate the participant, the researcher demonstrates his or her commitment
to the participant and conveys the importance/value of their participation in the study. If the
researcher-participant relationship is well developed, the participant will have a higher level of
trust in the researcher and will be likely to have more interest in the study and a positive
outcome. If such a relationship is developed and the participant is educated about the study
goals, the participant will more readily and effectively participate in the specific study activities.
For example, a study participant who understands why time/activity information is critical to
understanding exposure is likely to do a better job completing a time/activity log than a
participant with no interest in the outcome of the study. In addition, an informed participant may
have good suggestions for improving the study and the interactions with the participants and the
community that the researchers should listen to and adopt. Developing the research-participant
relationship and educating participants also should improve retention in longitudinal, repeated
measures studies because the participant feels that he or she is collaborating with the researcher
and are not merely a study "subject."
Similarly, providing education on the research study to the community should provide
significant benefits in terms of support to the research team and working with the team to
facilitate the study in their community to address both the scientific issues and the community's
concerns. If community leaders understand the research problem, the study goals, and the study
activities, they can more effectively articulate the community's concerns to the researchers and
integrate those issues into the study design. This will enhance their work with the research team
during the design phase and will enable them to more effectively advise and assist during the
implementation of the study.
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7.7 Reporting Study Results to the Participant and Community
Researchers need to develop the approach for reporting results to the participants,
community, stakeholders, media, and others during the initial planning of the study. There are no
clear guidelines for when and how to report study results (Parkin, 2004). In her systematic
review of guidelines and frameworks for reporting study results, Parkin determined that locating
guidance may be difficult and time consuming for researchers. She found agreement on the
importance of disseminating study results to produce public health benefits, but there is not a
consensus on when and how results should be reported to either communities or study
participants. Although she did not identify good guidance documents, she did identify some
common themes. The first was that researchers are becoming aware of the importance of
systematic planning of the research communications, planning that needs to be done early in the
study. Second, she determined that organizations are recognizing the importance of
communicating with communities. And, third, research professions are recognizing the
importance of research communication and their responsibilities.
Input should be solicited from community representatives, who can assist in developing
approaches that place the results in relevant contexts for the community and the participant.
One of the difficulties in reporting results is timely reporting because it generally takes a
long time to complete both the chemical analyses and the data analyses in large studies.
Researchers desire to report fully validated and analyzed data to study participants and to the
community. But, delay in reporting data can create a number of difficulties. Participants may
move before they receive results. They also may lose interest in the study, or more importantly,
lose trust in the researchers and the scientific research community if they do not receive their
results in a timely manner. Similar problems may occur in the community as community leaders
and representatives change. Community representatives may have expectations for data and
information that researchers cannot achieve. Therefore, it is important that researchers clearly
communicate with the participants and the community about what results will be provided and
when they will be delivered so that expectations do not differ from "reality."
There is a large body of literature on processes for
risk communication (e.g., see Covello et al., 1989, HHS,
2002, EPA, 2007a, and ASTDR, 2007). HHS has prepared
a useful document entitled "Communication in a Crisis:
Risk Communication Guidelines for Public Officials,
2002." It is available online and in hard copy, and includes
a chapter on communicating complex, scientific, and
technical information (HHS, 2002). They recommend
using clear, non-technical language, avoiding jargon, and
putting technical terms into frames of reference that the
public or other listeners can understand. More recently, Covello et al have developed a "message
mapping" approach for risk communication (EPA, 2007a). Message mapping is a process to
anticipate the questions likely to be asked after an incident and to prepare clear and concise
answers to the anticipated questions in advance. The approach builds on an understanding of
current communications practices (e.g., short messages averaging 27 words, soundbites of
around 9 seconds, the most frequently asked questions after an incident) and typical human
responses to crisis. The report lays out a series of steps to develop short, clear key messages to
address stakeholder concerns in advance. It also provides useful approaches for effectively
communicating the messages in times of crisis. It emphasizes that during a crisis, "people judge
the messenger before the message and they base their judgment in terms of trust." In times of
crises, opinions about trustworthiness hinge largely on perceptions of caring and empathy,
whereas competence and expertise are key factors when there is little or no stress. Figure 7-1 is
taken from the EPA, 2007a report and represents the relative importance of various factors in
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Text Box 7-5. Seven Cardinal Rules of
Risk Communication
Covello and Allen, 1988
1. Accept and involve the public as a partner.
2. Plan carefully and evaluate your efforts.
3. Listen to the public's specific concerns.
4. Be honest, frank, and open.
5. Work with other credible sources.
6. Meet the needs of the media.
7. Speak clearly and with compassion.
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influencing whether or not people trust a speaker in
times of crisis. Many of the principles and
processes for risk communications are applicable
for communication of research results from
observational studies, and the reader should consult
the risk communication literature.
ATSDR (2007) has A Primer on Health Risk
Communication Principles and Practices available
online that includes useful information for health
risk communications. Because ATSDR generally
responds to environmental issues identified by
individuals or communities, their guidance focuses
on communicating with individuals and
communities that perceive an imminent or
significant health risk because of a problem in the
community. Because ATSDR often enters a
community after a potential problem has been
identified, ATSDR communications are often
reactive, by necessity, rather than proactive.
Health Canada (2006) has recently published The Strategic Risk Communications
Framework. The focus of the effort is always the stakeholders. Health Canada's process aims to
involve the interested and affected parties at all points in a "dialogue-based" communication
process. (See Text Box 7-3.)
Reporting study results from observational human
exposure studies can be particularly challenging because
data on exposure concentrations and the factors impacting
exposure may be difficult to relate to a health outcome
that is relevant to the study participant. Health effects data
is often lacking for the concentrations at which chemicals
or their metabolites are measured in environmental or
biological media. This is especially true for studies of
many chemicals for which acceptable occupational
exposure levels have been established, but for which there
are not environmentally relevant standards for low-level
exposures. Williams (2004) describes an approach for
communication using comparative risk analyses. She
describes intrachemical comparisons, interchemical
comparisons, comparisons to background levels of risk, comparisons to theoretical risk or safety
levels, and risk comparisons to other actions or activities. Williams also includes an extensive list
of references for guidelines and other information on risk communication. Readers of this
document should refer to her manuscript to determine which approach may be applicable to their
particular study.
During longitudinal studies with repeated measurements over months, seasons, or years,
it is important that researchers commit to providing interim and ongoing results to participants
and the community as the study proceeds. It is important to maintain the researcher-participant
relationship throughout the study. This can be facilitated by keeping study participants informed
of the study progress and of the interim results.
Researchers also should recognize that there may be potential risks to the study
participants, third parties, and/or the community because of results generated from a study.
Listening/Caring/Empathy
50%
Honesty/ Dedication/
Openess Commitment
15-20% 15-20%
Competence/
Expertise
15-20%
Figure 7-1. Factors Influencing Trust In Times of Crisis
EPA, 2007
Text Box 7-3. Steps in Health Canada's
Risk Communication Framework
1. Identify the issue and its context—define
the opportunity and characterize the
situation.
2. Assess the risks and benefits—assess
stakeholder perception of the risks,
benefits, and tradeoffs.
3. Identify and analyze options—assess how
stakeholders perceive the options.
4. Select a strategy—develop and pretest
strategies, risk communications plans, and
messages.
Implement the strategy—implement risk
communications
6. Monitor and evaluate results—evaluate risk
communications effectiveness
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Therefore, revealing information to communities has to be done thoughtfully and with
appropriate preparation.
There are a variety of methods for providing study results to participants and the
community. Fact sheets can be used to describe the study and provide general study findings to
the community and stakeholders. Individualized fact sheets can be used to disseminate results to
the individual participants. Meetings with study participants have been used to disseminate study
information. Community meetings also can be used to provide updates on study progress and
general results.
Examples of the processes and the materials used for dissemination of information are
included in case studies described by Israel et al. (2005) and others conducting CBPR studies.
Overall study results generally are disseminated in peer-reviewed journal manuscripts
and study reports. The availability of results published in manuscripts and reports has been
greatly enhanced by posting them on Internet Web sites. For example, all EPA reports are now
available electronically via EPA's National Service Center for Environmental Publications Web
site (http://www.epa.gov/ncepihom/).
7.8 Reporting Unanticipated Results or Observations
The previous subsection discussed reporting of routine results from observational studies.
The communication plan should include processes and procedures for the dissemination of the
study results. Additionally, the communication plan needs to integrate with the data and safety
monitoring and oversight plans for the study and include a plan for reporting unanticipated
results or observations. Unanticipated results may include measurements of a chemical at a
concentration that exceeds what is considered to be an "acceptable" level in environmental
media or biological fluids. Unanticipated observations might include observation of the use of a
chemical not approved for indoor use, storage of chemicals in inappropriate containers, storage
of chemicals in places accessible by children, etc. Unanticipated results or observations may be
directly related to the research question being addressed in the study (e.g., measurements of
pesticide residues in a home) or nonstudy hazards (e.g., frayed electrical cords that may pose a
hazard to young children and residences). Section 4 discusses issues that may affect privacy and
confidentiality. Section 4.3 covers collateral observations of nonstudy-related hazards, including
those that States may mandate must be reported. Section 4.5 discusses the need for data and
safety monitoring and oversight, including the development of plans to report and react to
anticipated or unanticipated adverse events or conditions.
As part of the study implementation plan and the communication plan, researchers should
develop a protocol for how to identify contaminant measurements and exposures of "concern"
that should be reported to the study participant as quickly as possible because of the potential
risk associated with the exposure (see Section 4.5, Data and Safety Monitoring and Oversight,
and also Section 2.8, Establishing Criteria and Standards for Monitoring Scientific and Ethical
Issues During a Study.) The plan needs to include the protocol for making the determination and
the criteria that will be used as the threshold or "trigger" for reporting. The plans should describe
how the results will be reported to the participant and what additional action will be undertaken
to assist the participant in reducing their exposures. The first step in developing the protocol is to
identify what measurement will be used to identify exposures of concern. In observational
human exposure studies, this will generally be the chemical measurement in either
environmental or biological samples. For example, measurement of lead concentration in blood
would be an appropriate exposure metric study if the research question being addressed involves
lead exposure. The measurement is relatively simple and can be performed with a short
turnaround time. Similarly, measurements of chemicals in blood may be appropriate for other
persistent chemicals that have relatively long half-lives in blood. For nonpersistent chemicals,
biomarkers of exposure measured in urine or saliva may be appropriate exposure metrics to
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identify exposure of concern. For some chemicals (e.g., PM, VOCs, ozone) biomarkers of
exposure are either not available or difficult to measure or interpret. In these cases,
measurements in environmental media may be the best exposure metric. Whatever metric is
chosen, it is important that the chemical analyses can be performed relatively quickly to reduce
such exposures as quickly as possible.
The second, and more difficult, step in developing the reporting protocol is to determine
the level of concern that triggers reporting of the concentration to the study participant. For some
environmental media, such as drinking water, EPA (2007b) has established maximum
contaminant levels (MCLs) that can be used as triggers for reporting. For example, if the
researcher measures a level of arsenic in drinking water above 0.010 mg/L, he or she would be
expected to report the level to the study participant. For other environmental media, such as air,
there are few applicable standards. The National Ambient Air Quality Standards (NAAQS)
might be used for the criteria pollutants. Guidelines for occupational exposures, such as TLVs
and biological exposure indices (BEIs) published by the American Conference of Governmental
Industrial Hygienists (ACGIH, 2007) also may be used. TLVs are not standards; ACG1H
formulates a conclusion on the level of exposure that the typical worker can experience without
adverse health effects. Many people would argue that the TLVs are not conservative enough for
the average population, particularly not for vulnerable lifestages (e.g., children, the elderly) and
TLVs are only for exposure by inhalation. WHO (2005) also publishes air quality guidelines.
These types of guidelines can be used to advise study participants if their exposures are high
relative to the guidelines. Reporting levels should be conservative, but not so low that reporting
the level to the participant causes unwarranted concern and stress. For other environmental
media measured in observational human exposure studies, such as house dust or surface wipes,
the measurement results cannot be easily used to estimate exposures, and they are a poor metric
if used alone. An approach that is similar to comparison of measurements in environmental
media to available guidelines and standards is the comparison of measurements in biological
fluids to measurement data available from the National Health and Nutrition Examination Survey
(NHANES). For example, results of measurements of chemicals or their metabolites in urine or
blood can be compared to different percentiles (e.g., the 90th or 95th) reported in the NHANES
national reports (CDC, 2005). This type of comparison shows that the participant's
measurements are at the high end of the distribution of the NHANES data, suggesting that action
may need to be taken to mitigate exposures. However, researchers need to be judicious in the
selection of the exposure metric. Biomarkers in blood and biomarkers in urine can be very
different exposure metrics and may represent different aspects of the exposure event.
A more complex approach than using simple data comparisons, is to calculate a reporting
level defined as a chemical or metabolite concentration indicative of an absorbed dose greater
than that of a target level (for example one-tenth) of a lifetime reference dose (RfD) level. For a
pesticide, the absorbed dose could be estimated from the urinary pesticide metabolite level using
an approach similar to the methodology published by Fenske et al. (2000). This deterministic
approach to dose estimation allows direct back-calculation of doses from urinary metabolite
concentrations using few assumptions and is consistent with current pesticide regulatory
procedures for risk assessment. When using this approach, the research team will need to
determine how conservative the reporting level should be, as there are no guidelines available for
using this approach. If the concentrations of a metabolite measured in a study participant's urine
level are indicative of elevated exposures (i.e., above the reporting level), the researchers would
be expected to report the information to the participant and provide information or local contacts
that could assist in helping the participant identify sources of exposure and reduce their
exposures. Although this would seem to be a reasonable approach for some classes of chemicals,
the authors are not aware of reports of the use of this approach in the scientific literature.
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7.9 Anticipating and Responding to Criticism
As discussed in other parts of this document, in spite of researchers best intentions, there
may be situations that arise in which people's perceptions of the study design or implementation
plan are not accurate, or their opinions and beliefs about the ethical issues associated with a
study may not be in agreement with those of the research team and others involved in the study
(e.g., the peer review panel, the IRB). Just as it is not unreasonable to expect differences in
opinion on scientific approaches to an observational study, it is not unreasonable to expect
differences of opinion on ethical approaches. The researchers, therefore, should be prepared to
respond to criticism. The implementation plan and the communication plan should address how
the research team should anticipate study elements that may be criticized. During study
conceptualization, the research team should develop a list of potentially controversial study
elements (many of which are discussed in this document). For each study element, the research
team should describe how the ethical approaches to the study element were evaluated and
selected. Both the process and the rationale for selection of a particular approach should be
documented. At each step in the study planning and review process, the research team should
document discussions related to the specific element, considerations that were made, actions
taken, and justification for the actions. Input from research team members, internal reviewers,
external reviewers, community members, and others involved in the study should be documented
for controversial study elements. Similarly, for potentially controversial study elements, the
review and actions by the IRB should be documented. All of this information should be compiled
and documented for use in preparing a set of Q&As that can be used by the research team and
sponsoring organization to respond to criticism. When responding to criticism, establishing trust
and credibility are essential, as discussed previously. The public's perception of trust and
credibility is determined by the public's perceptions of the researchers' knowledge and expertise,
openness and honesty, and concern and care (Peters et al., 1997). These factors are important to
consider in developing the information and approach that will be used to respond to criticism.
There is a large volume of information available on "crisis communication" that the
reader can use to develop a plan for anticipating and responding to criticism (e.g., FCN, 2001;
ATSDR, 2007; HHS, 2002). The key is to be proactive and have a plan before any criticism is
raised.
7.10 Responding to the Media, Public Inquiries, and Other Stakeholders
Like crisis communications, the communication plan should include detailed plans for
how to interact with the stakeholders, the media, and the public. Standard approaches have been
developed for effective communications (e.g., FCN, 2002) with the media and will not be
included in this document. A proactive plan, open and transparent communications, and easily to
comprehend information will ensure effective communications with stakeholders and the public.
7.11 References
ACGIH (American Conference of Governmental Industrial Hygienists) (2007) Threshold Limit Values (TLVs) and
Biological Exposure Indices (BEIs) [online]. Available: http://www.acgih.org/tlv/ [accessed 13 June 2007],
AldersonP (1995). Will you help us with our research'.' Archives of Disease in Childhood 72(6):541-542.
Anderson B, Hall B (1995). Parents' perceptions of decision making for children. J Law Med Ethics 23(1): 15-9.
ATSDR (Agency for Toxic Substances and Disease Registry) (2007). A Primer on Health Risk Communication
Principles and Practices [online publication]. Available: http://www.atsdr.cdc.gov/risk/riskprimer/ [accessed 12
June 2007],
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1 CDC (Centers for Disease Control and Prevention) (2005). Third National Report on Human Exposure to
2 Environmental Chemicals. National Center for Environmental Health, Atlanta, GA, NCEH Pub. No. 05-0570.
3
4 Covello V, Allen F (1988). Seven Cardinal Rules of Risk Communication. U.S. Environmental Protection Agency,
5 Office of Policy Analysis, Washington, DC.
6 Covello VT, McCallum DB, Pavlova M (eds) (1989). Effective Risk Communication: the role and responsibility of
7 Government and Non-Government Organizations. New York. NY: Plenum Press.
8 FCN (Federal Communicators Network) (2001). Communicators Guide For Federal, State, Regional, and Local
9 Communicators by the Federal Communicators Network. Available:
10 http://www.publicforuminstitute.org/activities/2002/fcn/commguid.pdf [accessed 12 June 2007],
11 Fenske RA, Kissel JC, Lu C, DA Kalman DA, Simcox NJ, Allen EH, Keifer MC (2000) Biologically based
12 pesticide dose estimates for children in an agricultural community. Environmental Health Perspectives 108:515-520.
13
14 Health Canada (2006). The Strategic Risk Communications Framework. Available: www.riskcoinmunicalions.ac.ca
15 [accessed 18 September 2007]
16 IOM (Institute of Medicine) (2002). Responsible Research: A Systems Approach to Protecting Research
17 Participants. Daniel D. Federman, Kathi E. Hanna, and Laura Lyman Rodriguez, (eds). Washington, DC: The
18 National Academies Press.
19
20 Israel BA, Eng E, Schulz AJ, Parker EA (eds) (2005). Methods in Community-Based Participatory Research for
21 Health. San Francisco, CA: Jossey-Bass.
22 NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for
23 the NIH Director from the Director's Council of Public Representatives (COPR). National Institutes of Health,
24 Director's Council of Public Representatives, January 14. 2005. Available:
25 http://copr.nih.gov/reports/public trust.asp [accessed June 20071.
26
27 NRC (National Research Council) (2004) Research Priorities for Airborne Particulate Matter: IV. Continuing
28 Research Progress. Washington, DC: The National Academies Press. Available:
29 http://books.nap.edu/openbook.php7record id= 10957 [accessed 16 August 2007],
30
31 Parkin RT (2004). Communications with research participants and communities: foundations for best practices. J
32 Expo Anal Environ Epidemiol 14(7):516-23.
33 Peters RG, Covello VT. McCallum DB (1997). The determinants of trust and credibility in environmental risk
34 communication: an empirical study. Risk Anal 17(l):43-54.
35 U.S. EPA (Environmental Protection Agency) (2007a). Effective Risk and Crisis Communication during Water
36 Security Emergencies. Summary Report of EPA Sponsored Message Mapping Workshops, Covello, V, S
37 Minamyer. K Clayton authors, EPA/600/R-07-027, Washington DC. Available
38 http:/A\ w w.cpa.gov/NHSRC/pubs/reportCrisisCom040207.pdf.
39 U.S. EPA (U.S. Environmental Protection Agency) (2007b). Drinking Water Contaminants. Environmental
40 Protection Agency. Available: http://www.epa.gov/safewater/contaminants/index.html [accessed 13 June 2007],
41
42 U.S. HHS (U.S. Department of Health and Human Services) (2002). Communicating in a Crisis. Available:
43 http://www.riskcommunication.samhsa.gov/index.htm [accessed 13 June 20071.
44 Williams PR (2004) Health risk communication using comparative risk analyses. J Expo Anal Environ Epidemiol
45 14(7):498-515.
46 World Health Organization (2005). WHO Air Quality Guidelines Global Update 2005. Available:
47 http://www.euro.who.int/Document/E87950.pdf [accessed 13 June 2007],
48 7.11.1 Additional Information Resources
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U.S. EPA. (Environmental Protection Agency). (1994) Seven cardinal rules of risk communication. Office of Policy
Analysis. Washington, D.C: EPA/OP A/87/020.
U.S. Public Health Service. (1995) Risk communication: working with individuals and communities to weigh the
odds. Prevention Report: Feb/Mar. Available online at
http://odphp.osophs.dhhs. gov/pubs/prevrpt/Archives/95fml .htm
U.S. EPA (Environmental Protection Agency). (2006a) (External Review Draft) Considerations for Developing Al-
ternative Health Risk Assessment Approaches for Addressing Multiple Chemicals, Exposures and Effects. Washing-
ton, DC.
U.S. EPA (Environmental Protection Agency). (2006b) Paper on tribal issues related to tribal traditional lifcw a> s.
risk assessment, and health and well being: Documenting what we've heard. The National EPA-Tribal Science
Council.
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APPENDIX A
Charge and Participants for the Expert Panel Workshop,
November 28 and 29, 2006, and the Charge and Participants for the
External Peer Review by the HSRB
Expert Panel Workshop
The charge to the Expert Panel Workshop members was as follows.
The panel is asked to consider these issues prior to the workshop in preparation
for discussion during this workshop meeting:
1. Provide recommendations on the content and organization of the document.
a. Identify the major scientific and ethical areas/issues in the design and
implementation of observational human exposure measurement studies
that should be considered for inclusion in the document.
b. Identify specific elements in each of these major areas that should be
considered for inclusion in the document.
c. Provide recommendations on the type and level of information that should
be considered for inclusion in the document when describing state-of-the-
science approaches, methods, techniques, or standards.
d. Provide recommendations on the criteria that should be considered when
evaluating and identifying the state-of-the-science for the approaches,
methods, techniques, or standards.
2. Provide recommendations and listings of sources of information for
developing the document including case studies where available.
3. Identify at least ten specific elements of the design and implementation of
these studies that the panel considers to have the most uncertainty with regard
to the "state-of-the-science," discuss these elements, and provide
recommendations on state-of-the-science approaches for them.
The members of the Expert Panel were as follows.
Timothy Buckley (Chair)
Division of Environmental Health Sciences
School of Public Health
Ohio State University
Columbus, OH
Sophie Balk
Attending Pediatrician
Children's Hospital at Montefiore
Professor of Clinical Pediatrics
Albert Einstein College of Medicine
Bronx, NY
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David Carpenter
Director, Institute of Health and Environment
University of Albany, SUNY
Rensselaer, NY
Giselle Corbie-Smith
Department of Social Medicine
University of North Carolina-Chapel Hill
Chapel Hill, NC
Alan Fleischman
Senior Advisor
The New York Academy of Medicine
New York, NY
Natalie Freeman
Center for Environmental and Human Toxicology
Department of Physiological Sciences
University of Florida
Gainesville, FL
Loretta Jones
Healthy African American Families
Los Angeles, CA
Bruce Lanphear
Professor of Pediatrics and of Environmental Health
Cincinnati Children's Hospital Medical Center
Division of General and Community Pediatrics
Cincinnati, OH
Michael Lebowitz
University of Arizona
Colleges of Public Health and Medicine
Arizona Health Sciences Center, MEZCOPH
Tucson, AZ
Jerry Menikoff
Department of History and Philosophy of Medicine
University of Kansas Medical Center
Kansas City, KS
Rebecca Parkin
Associate Dean for Research and Public Health Practice
Professor of Environmental and Occupational Health
School of Public Health and Health Service
George Washington University Medical Center
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Human Subjects Review Board Peer Review
[THE FOLLOWING TEXT WILL BE ADDED AS THE PROCESS IS COMPLETED]
This document is undergoing review by EPA's Human Subjects Review Board (HSRB).
The charge to the HSRB was as follows. TBD
The members of the HSRB that reviewed this document were: ....
[TO BE COMPLETED]
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APPENDIX B
Recommended Content of a Human Subjects Protocol from the
Council for International Organizations of Medical Sciences
Under the World Health Organization
International Ethical Guidelines for Biomedical Research Involving
Human Subjects (CIOMS, 2002)
Items Relevant to Observational Human Exposure Studies
(1) Titl e of the study
(2) A summary of the proposed research in lay or nontechnical language
(3) A clear statement of the justification for the study
(4) The investigators' views of the ethical issues and considerations raised by the study and, if
appropriate, how it is proposed to deal with them
(5) Summary of previous studies on the research problem, including unpublished studies
known to the investigators, and information on previously published research on the topic
(6) A statement that the principles of the Belmont Report and requirements specified in 40
CFR 26 will be implemented
(7) An account of previous submissions of the protocol for ethical review and their outcome
(8) A brief description of the site(s) where the research is to be conducted, including
information about the adequacy of facilities for the safe and appropriate conduct of the
research, and relevant demographic and epidemiological information about the population
to be studied
(9) Name and address of the funding organization, research partners, and collaborators
(10)Names, addresses, institutional affiliations, qualifications, and experience of the principal
investigator and other investigators
(1 l)The objectives of the study, its hypotheses or research questions, its assumptions, and its
variables
(12) A detailed description of the design of the study
(13) The number of research subjects needed to achieve the study objective, and how this was
statistically determined
(14) The criteria for inclusion or exclusion of potential subjects, and justification for the
exclusion of any groups on the basis of age, sex, social or economic factors, or for other
reasons
(15)The justification for involving as research subjects any persons with limited capacity to
consent or members of vulnerable social groups, and a description of special measures to
minimize risks and discomfort to such subjects
(16) The process of recruitment (e.g., advertisements) and the steps to be taken to protect
privacy and confidentiality during recruitment
(17) Description and explanation of any and all interventions
(18) Measurements to be performed in the study, including environmental and biological
sample collection, and other data and information that will be collected
(19) If applicable, clinical and other tests involving the study participants that are to be carried
out
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(20)Rules or criteria according to which subjects may be removed from the study or the study
may be terminated
(21)Methods of recording and reporting adverse events or reactions, and provisions for dealing
with complications
(22) The potential benefits of the research to subjects and to others
(23) The expected benefits of the research to the population, including new knowledge that the
study might generate
(24) The means proposed to obtain individual informed consent and the procedure planned to
communicate information to prospective subjects, including the name and position of the
person responsible for obtaining consent
(25) When a prospective subject is not capable of informed consent, satisfactory assurance that
permission will be obtained from a duly authorized person, or, in the case of a child who
is sufficiently mature to understand the implications of informed consent but has not
reached the legal age of consent, that knowing agreement, or assent, will be obtained, as
well as the permission of a parent, or a legal guardian or other duly authorized
representative.
(26) An account of any economic or other compensation or incentives to prospective subjects
to participate, such as offers of cash payments, gifts, or free services or facilities, and of
any financial obligations assumed by the subjects, such as payment for medical services
(27)Plans and procedures, and the persons responsible, for communicating to subjects
information arising from the study (on harm or benefit, for example), or from other
research on the same topic, that could affect subjects' willingness to continue in the study
(28)Plans to inform subjects about the results of the study
(29) The provisions for protecting the confidentiality of personal data, and respecting the
privacy of subjects, including the precautions that are in place to prevent disclosure of the
results of a subject's genetic tests to immediate family relatives without the consent of the
subject
(30)Information about how the code, if any, for the subjects' identity is established; where it
will be kept; and when, how, and by whom it can be broken in the event of an emergency
(31) Any foreseen further uses of personal data or biological materials
(32) A description of the plans for statistical analysis of the study, including plans for interim
analyses, if any, and criteria for prematurely terminating the study as a whole if necessary
(33) A list of the references cited in the protocol
(34) The source and amount of funding of the research: the organization that is sponsoring the
research and a detailed account of the sponsor's financial commitments to the research
institution, the investigators, the research subjects, and, when relevant, the community
(3 5) The arrangements for dealing with financial or other conflicts of interest that might affect
the judgment of investigators or other research personnel: informing the institutional
conflict-of-interest committee of such conflicts of interest; the communication by that
committee of the pertinent details of the information to the ethical review committee; and
the transmission by that committee to the research subjects of the parts of the information
that it decides should be passed on to them
(36) The time schedule for completion of the study
(37) Particularly in the case of an industrial sponsor, a contract stipulating who possesses the
right to publish the results of the study, and a mandatory obligation to prepare with, and
submit to, the principal investigators the draft of the text reporting the results
(38) Circumstances in which it might be considered inappropriate to publish findings, such as
when the findings of any study may present risks to, or stigmatize, the interests of a
community or population or of a racially or ethnically defined group of people
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1 (39) A statement that any proven evidence of falsification of data will be dealt with in
2 accordance with the policy of the sponsor to take appropriate action against such
3 unacceptable procedures
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APPENDIX C
Recommendations for Enhancing Public Trust from
Report and Recommendations on Public Trust in Clinical Research
for the NIH Director from the Director's Council of Public
Representatives (National Institutes of Health, Director's Council of
Public Representatives, January 14, 2005; NIH. 2005)
Building Trust Through Community Partnerships
Recommendation 1: Incorporate into the NIH mission and philosophy that it values the
involvement of the community in research and create language that expresses this value.
Recommendation 2\ Encourage change in the culture of the scientific community to ensure that
medical research is viewed in the context of a long-term commitment to the community, not a
one-time research study.
Recommendation 3: Investigate ways to provide mechanisms that allow for followup health care
when a clinical trial or treatment ends.
Building Relationships with Patients (Participants) [True partnerships with patients may
not be possible, but bidirectional relationships must be enhanced.]
Recommendation 4\ Educate and reorient the current research community to the importance of
treating the public as a partner in the research process.
Recommendation 5: Set the expectation across the entire research community, NIH funded
research and beyond, that study results and outcomes should be shared with the research
participants and the larger community promptly and consistently. This will ensure translational
research.
Building Partnerships with Community Providers
Recommendation 6: Take action to interest community providers in clinical research and
maintain their involvement.
Recommendation 7: Provide incentives (not just financial) for primary health care providers and
community specialists to play a role in clinical trials.
Building Trust in Scientists
Recommendation X: Engage researchers, educators, and academic institutions in incorporating
the public's perspective consistently at every level of training and in both the conduct of clinical
research and the publication of findings from that research.
Recommendation 9: Focus on educational strategies to help patients and communities better
understand clinical research. This will help scientists because educating the public will empower
and prepare individuals to be informed partners in the clinical research process. An informed and
trusting public will enhance research participation.
Building Trust in the NIH and Scientific Research
Recommendation 10: Continue to develop and fund efforts to build a national identity for the
NIH based on what NIH does best—research and education—as a basis for enhancing public
trust in clinical research.
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1 Recommendation 11: Review the role and impact of Institutional Review Boards and other
2 patient protections in the clinical research process because the public views these protections as
3 less effective than they should be.
4
5 Recommendation 12\ Document and publish "best practices" from efforts to reengineer the
6 clinical research enterprise as soon as the NIH begins to see results, so that progress in
7 improving public trust in medical research grows rapidly and steadily.
8
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3 APPENDIX D
4
5 List of Acronyms and Abbreviations
6
7 AAP American Academy of Pediatrics
8 ACGIH American Conference of Governmental Industrial Hygienists
9 ATSDR Agency for Toxic Substances and Disease Registry
10 BEI biological exposure index
11 CAB Community Advisory Board
12 CBPR community-based participatory research
13 CDC Centers for Disease Control and Prevention
14 CFR Code of Federal Regulations
15 CIOMS Council for International Organizations of Medical Sciences
16 COPR NIH Director's Council of Public Representatives
17 CPSC Consumer Product Safety Commission
18 DHDC Detroit Hispanic Development Corporation
19 DHEW U.S. Department of Health, Education, and Welfare
20 DMOC data monitoring and oversight committee
21 DNA deoxyribonucleic acid
22 DSMB data safety monitoring board
23 DSMP data and safety monitoring plans
24 DWEJ Detroiters's Working for Environmental Justice
25 EHCRB environmental health and community review boards
26 EPA U.S. Environmental Protection Agency
27 ERG Eastern Research Group
28 FCN Federal Communicators Network
29 FDA Food and Drug Administration
30 HHS U.S. Department of Health and Human Services
31 HSRRO Human Subjects Research Review Official
32 HUD U.S. Department of Housing and Urban Development
33 ICR information collection request
34 IOM Institute of Medicine
35 IRB Institutional Review Board
36 MCL maximum contaminant level
37 NAAQS National Ambient Air Quality Standards
38 NAS National Academy of Sciences
39 NBAC National Bioethics Advisory Commission
40 NCI National Cancer Institute
41 NCS National Children's Study
42 NEI National Eye Institute
43 NEJAC National Environmental Justice Advisory Council
44 NERL National Exposure Research Laboratory
45 NHANES National Health and Nutrition Examination Survey
46 NHLBI National Heart Lung and Blood Institute
47 NHRPAC National Human Research Protections Advisory Committee
48 NIH National Institutes of Health
49 NRC National Research Council
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OHRP Office for Human Research Protections
OMB Office of Management and Budget
OSMB observational study monitoring boards
PM particulate matter
Q&As questions and answers
QAPP quality assurance project plan
RfD reference dose
TEAM Total Exposure Assessment Methodology
TLV threshold limit value
VOC volatile organic compounds
WCDC Warren Conner Development Coalition
WHO World Health Organization
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2 APPENDIX E
3
4 GLOSSARY
Agent
A chemical, mineralogical, biological, or physical entity that may cause
deleterious effects in an organism after the organism is exposed to it
[EPA/600/Z-92/001, May 1992],
Assent
A child's affirmative agreement to participate in research. Mere failure to
object should not, absent affirmative agreement, be construed as assent
[45 CFR 46.402(d)],
Autonomy
The capability and capacity to govern oneself
Beneficence
The ethical obligation to maximize benefits and to minimize harms. This
principle gives rise to norms requiring that the risks of research be
reasonable in light of the expected benefits, that the research design be
sound, and that the investigators be competent both to conduct the research
and to safeguard the welfare of the research subjects. Beneficence further
proscribes the deliberate infliction of harm on persons; this aspect of
beneficence is sometimes expressed as a separate principle, nonmaleficence
(do no harm).
Child
A person who has not attained the age of 18 years [40 CFR 26.202(a)],
Collateral
observations
Potentially unsafe hazards, conditions, or situations unrelated to the research
study that are observed by the research staff
Common Rule
The Common Rule is a short name for "The Federal Policy for the Protection
of Human Subjects." It was adopted by more than a dozen Federal
departments or agencies in 1991, with EPA adapting it in Title 40 CFR Part
26 Subpart A.
Community-
based
participatory
research (CBPR)
Collaborative research with a community in which the community is
involved in all phases of the research. A fundamental concept is that the
research aims to combine knowledge with action and to achieve social
change to improve health outcomes and eliminate health disparities.
Confidentiality
The keeping safe and/or not redisclosing by one of the parties in a
confidential relationship of information that originally was disclosed in the
confidential relationship
Environmental
justice
The fair treatment and meaningful involvement of all people regardless of
race, color, national origin, or income with respect to the development,
implementation, and enforcement of environmental laws, regulations, and
policies (U.S. EPA, 2005)
Exposure
Contact of a chemical, physical, or biological agent with the outer boundary
of an organism [e.g., a person]. Exposure is quantified as the concentration
of the agent in the medium in contact integrated over the time duration of
that contact. (The definition is taken from Guidelines for Exposure
Assessment [EPA/600/Z-92/001, May 1992]).
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Exposure
concentration
The exposure mass divided by the contact volume or the exposure mass
divided by the mass of contact volume depending on the medium
Exposure
duration
The length of time over which continuous or intermittent contacts occur
between an agent and a target. For example, if an individual is in contact
with an agent for 10 min per day for 300 days over a 1-year time period, the
exposure duration is 1-year.
Exposure event
The occurrence of continuous contact between an agent and a target.
Exposure
pathway
The course an agent takes from the source to the target
Exposure route
The way an agent enters a target after contact (e.g., by ingestion, inhalation,
or dermal absorption).
Human subject
A living individual about whom an investigator (whether protessibnal or
student) conducting research obtains
(1) data through intervention or interaction with the individual, or
(2) identifiable private information [40 CFR 26.102(f)]
Informed
consent
A potential participant's autonomous authorization to participate in the
research. The three pillars of valid informed consent are: (1) information, (2)
comprehension, and (3) voluntary participation.
Institutional
review board
(IRB)
An IRB established in accord with and for the purposes expressed in EPA's
Policy for Protection of Subjects in Human Research conducted and
supported by EPA [40 CFR 26.102(g)]
Justice
The ethical obligation to treat each person in accordance with what is due to
him or her. In the ethics of research involving human subjects, the principle
refers primarily to distributive justice, which requires the equitable
distribution of both the burdens and the benefits of participation in research.
Differences in di stribution of burdens and benefits are justifiable only if they
are based on morally relevant distinctions between persons.
Minimal risk
The probability and magnitude of harm or discomfort anticipated in the
research are not greater in and of themselves than those ordinarily
encountered in daily life or during the performance of routine physical or
psychological examinations or tests [40 CFR 26.102(i)].
Nonmaleficence
The proscription of deliberate infliction of harm on persons
Observational
human exposure
study
Studies that involve collection of human exposure data (including
environmental, biological, survey, activity, and various other forms of data)
under real-world field conditions during normal participant day-to-day
activities, with no additional exposures to the chemical being studied
because of participation in the study. The studies involve interaction with
study participants but do not involve intervention or manipulation of the
factors being studied, and there is no attempt by the researcher to affect the
outcome.
Observational
research
Any human research that does not meet the definition of research involving
intentional exposure of a human subject [40 CFR 26.302]
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Privacy
Control over the extent, timing, and circumstances of sharing oneself
(physically, behaviorally, or intellectually) with others
Research
A systematic investigation, including research development, testing, and
evaluation, designed to develop or contribute to generalizable knowledge
Research
involving
intentional
exposure of a
human subject
A study of a substance in which the exposure to the substance experienced
by a human subject participating in the study would not have occurred but
for the human subject's participation in the study [40 CFR 26.202(b)]
Respect for
persons
A fundamental ethical value that is the basis of much of modern bioethical
thought and regulation. The concept incorporates at least two fundamental
ethical considerations, namely
(1) respect for autonomy, which requires that those who are capable of
deliberation about their personal choices should be treated with respect for
their capacity for self-determination; and
(2) protection of persons with impaired or diminished autonomy, which
requires that those who are dependent or vulnerable be afforded security
against harm or abuse.
Source
The origin of an agent for the purposes of an exposure assessment
Stakeholder
A person or group who has a valid interest in an activity, who can affect or is
affected by the activity, and who stands to gain or lose depending on the
decisions implemented
Stressor
Any entity, stimulus, or condition that can modulate normal functions of the
organism or induce an adverse response (e.g., agent, lack of food, drought)
Vulnerability
A substantial incapacity to protect one's own interests owing to such
impediments as lack of capability to give informed consent, lack of
alternative means of obtaining medical care or other expensive necessities, or
being a junior or subordinate member of a hierarchical group. Accordingly,
special provision must be made for the protection of the rights and welfare of
vulnerable persons.
Vulnerable
groups
Populations extended additional human subjects protections, like children,
individuals with questionable capacity to consent, prisoners, fetuses and
pregnant women, the terminally ill, students and employees, and comatose
patients, etc.
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SCIENCE
^PDA PRESORTED STANDARD
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United States EPA
Environmental Protection
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Office of Research and Development (81 OR)
Washington, DC 20460
Official Business
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