United States EPA Science Advisory EPA-SAB-EC-02-008
Environmental Board (1400A) May 2002
Protection Agency Washington, DC www.epa.gov/sab
vvEPA Interim Review of the
Participate Matter (PM)
Research Centers of the
USEPA: An EPA Science
Advisory Board Report
A REVIEW BY THE PM
RESEARCH CENTERS
INTERIM REVIEW PANEL OF
THE EXECUTIVE COMMITTEE
OF THE US EPA SCIENCE
ADVISORY BOARD (SAB)
-------
5 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
• WASHINGTON, D.C. 20460
May 24, 2002
OFFICE OF THE ADMINISTRATOR
SCIENCE ADVISORY BOARD
EPA-SAB-EC-02-008
Honorable Christine Todd Whitman
Administrator
U.S. Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460
Subject: Interim Review of the Parti culate Matter (PM) Research Centers: An SAB
Report
Dear Governor Whitman:
On February 11 and 12, 2002 the PM Centers Interim Review Panel (Panel) of the US
EPA Science Advisory Board (SAB) met to review the Agency's PM Research Centers program
as a mechanism for generating research results that can inform Agency decision-making. The
request to provide this advice was received from the National Center for Environmental
Research (NCER) in the Office of Research and Development (ORD).
In 1998 the NCER, under its Science to Achieve Results (STAR) Program, issued a
competitive request for applications that resulted in the support of five PM Research Centers for
up to five years, with a total of $8M expended in the first year of the program. The Centers were
to address research needs in the areas of exposure, dosimetry, extrapolation modeling,
toxicology, and epidemiology.
As it considers budget formation for FY04 and beyond, NCER needs to decide whether
or not to continue with the concept of PM Research Centers beyond the current funding cycle, or
whether there might be a better way of generating the research results that will inform Agency
decision-making on PM issues. Insufficient time has passed for the Centers - individually or
collectively - to have generated a body of research results that could allow a definitive answer to
this question based on "outputs", per se. However, considerable experience has been gained
with the Centers concept to date that can allow an assessment of the overall utility of this
approach, if not of the individual Centers themselves.
This emphasis on the assessment of the concept of Centers-based research is reflected in
the Charge to the Panel that consists of an overall question, plus six specific questions:
-------
Overall Question:
Is it likely that the PM Centers program will be sufficiently successful to merit
continuation in FY 2004 and beyond? In which areas, to what extent, and for
what reasons is a PM Centers program beneficial? Where it is not, what
improvements can be made?
Specific Questions:
1 .Recognizing the PM Centers program is barely at its halfway point, what important
research findings (or promising investigations) have been made that would not
have occurred otherwise? What unique aspect(s) of a Centers program enabled
such actions to be taken.
2. To what extent has the direction or focus of research shifted as a result of the multi-
disciplinary interactions within the Center (i.e., findings in one department
influence researchers in another to change direction or emphasis). To what extent
have changes in research direction or emphasis been influenced by Science
Advisory Committee reviews, interactions with other PM Centers, or interactions
with the broader PM research community? Which factors have been most
influential?
3. How successful are Centers in communicating their findings to the public and
specifically, to those who directly use their research? Is it clear that the work has
been supported by the PM Centers program?
4. How, if at all, does a PM research centers program facilitate agreement or consensus
on protocols or procedures to enable more direct comparison of results among
research institutions or centers?
5. How, if at all, does a PM research centers program leverage or maximize use of
resources through sharing expensive equipment, samples, data, etc.?
6. How is the program perceived within and outside the research community? Does a
research center have greater visibility, and if so, what is the impact?
Detailed answers to these questions are found in the body of the report. The thrust of the
answers are captured in the following major findings and recommendations:
1. The PM Centers Program a) has produced benefits beyond those normally found in
individual investigator-initiated grants and b) is likely to continue to provide such
benefits throughout its current funding cycle. Overall, the Panel found that the
program merits continuation beyond FY04 — through a new, fully-competitive
round of applications — as one part of a diverse PM research portfolio at the
Agency.
2. The Panel identified several specific advantages that the Centers approach offers over
more traditional research mechanisms, including enhanced flexibility and
adaptability leading to improved timeliness, ability to conduct higher-risk pilot
and validation efforts, study designs enhanced by intra-Center multi-disciplinary
integration, and improved leveraging of the Agency's and the Centers' research
resources.
-------
3. The Panel identified several ways in which a new round of Center grants could be
enhanced, either by expanding upon activities already underway or by
undertaking new efforts. Importantly, the Panel noted that while there are evident
benefits of integration within and across Centers, there are also potential
challenges to insure that the work of the Centers does not become isolated from
that of other researchers within the Agency and in the academic community. Key
enhancements include the following:
a. Continued attention in a new request for applications (RFA) to focusing
the Centers' efforts on the most critical PM needs, as determined at
that time in reviews of research progress and needs by the National
Research Council and US EPA
b. The development of an informal, but overarching, mechanism of
scientific advice to the program
c. Enhanced opportunities for cross-fertilization of ideas with EPA's
intramural researchers and the broader extramural community
d. Enhanced interaction between the research conducted at the Centers and
ongoing intensive air quality monitoring efforts, such as those at
the Agency's supers!tes and others
e. The provision of systems and resources from the start for inter-Center
integration efforts.
We appreciate the opportunity to review and provide advice on the PM Research Centers
program. We want to acknowledge the valuable assistance of the Agency staff who supplied us
with information that is a part of the public record of our meeting. The documentation,
presentations and availability of the Center Directors to answer questions during our public
meeting were also very helpful.
We look forward to your response to this report.
Sincerely,
/Signed/ /Signed/
Dr. William H. Glaze, Chair Mr. Daniel Greenbaum, Chair
EPA Science Advisory Board PM Research Centers Interim Review Panel
EPA Science Advisory Board
-------
NOTICE
This report has been written as part of the activities of the EPA Science Advisory Board,
a public advisory group providing extramural scientific information and advice to the
Administrator and other officials of the Environmental Protection Agency. The Board is
structured to provide balanced, expert assessment of scientific matters related to problems facing
the Agency. This report has not been reviewed for approval by the Agency and, hence, the
contents of this report do not necessarily represent the views and policies of the Environmental
Protection Agency, nor of other agencies in the Executive Branch of the Federal government, nor
does mention of trade names or commercial products constitute a recommendation for use.
Distribution and Availability: This EPA Science Advisory Board report is provided to the EPA
Administrator, senior Agency management, appropriate program staff, interested members of the
public, and is posted on the SAB website (www.epa.gov/sab). Information on its availability is
also provided in the SAB's monthly newsletter {Happenings at the Science Advisory Board).
Additional copies and further information are available from the SAB Staff [US EPA Science
Advisory Board (1400A), 1200 Pennsylvania Avenue, NW, Washington, DC 20460-0001; 202-
564-4533].
-------
U.S. Environmental Protection Agency
EPA Science Advisory Board
Executive Committee
Particulate Matters Interim Review Panel*
CHAIR
Mr. Daniel Greenbaum, President, Health Effects Institute, Boston, MA
EC MEMBERS
** Dr. Philip Hopke, Bayard D. Clarkson Distinguished Professor, Department of Chemical
Engineering, Clarkson University, Potsdam, NY
Also Member: Clean Air Scientific Advisory Committee
Research Strategies Advisory Committee
OTHER SAB MEMBERS
Dr. Paul J. Lioy, Associate Director and Professor, Environmental and Occupational
Health Sciences Institute, UMDNJ - Robert Wood Johnson Medical School,
Piscataway, NJ
Member: Advisory Council on Clean Air Compliance Analysis
Dr. Maria Morandi, Assistant Professor of Environmental Science, University of Texas,
Houston, TX
Member: Research Strategies Advisory Committee
CONSULTANTS
Dr. Michael Brauer, Associate Professor, School of Occupational and Environmental
Hygiene, The University of British Columbia, Vancouver, British Columbia,
Canada
Dr. Bert Brunekreef, Professor of Environmental Epidemiology, Institute for Risk
Assessment Sciences, Utrecht University, Utrecht,, The Netherlands
Dr. Kenneth Donaldson, Professor and Research Director, Biomedicine Research Group,
School of Life Sciences, Napier University, Edinburgh, Scotland, United
Kingdom
Dr. Carol Henry, Vice President, Science and Research, American Chemistry Council,
Arlington, VA
Dr. Patrick Kinney, Associate Professor, Div. Environmental Health Sciences, School of
Public Health, Columbia University, New York, NY
11
-------
Dr. Shankar Prasad, Community Health Advisor to the Chairman, Office of Community
Health, California Air Resources Board, Sacramento, CA
Dr. Ronald Wyzga, Technical Executive, Air Quality Health and Risk, Electric Power
Research Institute, Palo Alto, CA
EPA SCIENCE ADVISORY BOARD STAFF
Dr. Donald Barnes, Designated Federal Officer
Ms Betty Fortune, Office Assistant
Ms. Diana Pozun, Program Specialist
* Members of this SAB Panel consist of
a. SAB Members: Experts appointed by the Administrator to serve on one of the SAB
Standing Committees.
b. SAB Consultants: Experts appointed by the SAB Staff Director to a one-year term to
serve on ad hoc Panels formed to address a particular issue.
** Dr. Hopke participated in the public meeting of the Panel and contributed material to an early
draft of this report. Subsequently, he became associated with the Rochester PM Research
Center and resigned from the Panel. Dr. Hopke did not participate in the final
deliberations of the Panel and is not a party to the Panel's final report.
in
-------
TABLE OF CONTENTS
1. INTRODUCTION 1
1.1 Background 1
1.2 Charge to the Committee 2
1.3 SAB Review Process 3
1.4 Format of this Report 3
2. RESPONSE TO THE CHARGE 4
2.1 Overall Question 4
2.1.1 Is it likely that the PM Centers program will be sufficiently successful to merit
continuation beyond 2004? 4
2.1.2 In which areas, to what extent, and for what reasons is a PM Centers program beneficial? 4
2.1.3 What improvements can be made in the Centers Program? 7
2.2 Specific Charge Questions 9
2.2.1 Results to-date 9
2.2.2 Communications 21
2.2.3 Inter-Center interaction 22
2.2.4 Leveraging 24
2.2.5 Perception and visibility 25
3. FINDINGS AND RECOMMENDATIONS 26
APPENDIX A - ACRONYMS A-l
APPENDIX B - A MORE DETAILED DESCRIPTION OF THE SAB PROCESS B-l
APPENDIX C - ABSTRACT C-l
IV
-------
1. INTRODUCTION
1.1 Background
As one of its first and most important environmental legislative actions, the U.S.
Congress passed the Clean Air Act (CAA) that authorizes the US Environmental Protection
Agency (Agency) to conduct research, assess findings, and develop and implement regulations to
control pollutants in the air that adversely impact human health and the environment. For the
past thirty years the Agency has used this authority [modified by the Clean Air Act Amendments
(CAAA) of 1990], in part, to establish a vigorous National Ambient Air Quality Standards
(NAAQS) program. As a result, the Agency has implemented a costly, but effective, regulatory
program to reduce the negative impacts of a series of air pollutants.
One of the key air pollutants is "particulate matter" (PM), airborne microscopic particles
of whatever composition and shape.
From the earliest days of the Agency, public support was high for the control of "dirty
air"; i.e., black, sooty emissions from power plants, industrial facilities, and trucks and
automobiles. This support was soon translated into regulations to monitor air concentrations and
implement control of emissions that contributed to Total Suspended Particulate (TSP) matter,
without a specific size classification. This standard was changed in the late 1980s to include a
size criterion that included particles with mass median diameters (MMD) of 10 microns or less
(PM10), in recognition of the inhalability of such particles, as compared to those larger than 10
microns. Subsequent research revealed that exposures to PM at the so-called PM10 standard
posed unacceptable risks to human populations. As more research results became available,
pressure mounted to apply additional monitoring requirements and controls on emissions of
smaller-sized PM; specifically, in the MMD 2.5 micron range, on the basis that particles of this
size are more likely to penetrate to the respiratory regions of the lung and remain there for longer
periods of time. The Agency and the country are currently in the process of implementing these
new PM2.5 regulations.
Scientific research is playing a large role in monitoring and characterizing PM2.5,
establishing its effects on exposed populations, and developing effective control measures to
reduce its concentrations in the atmosphere. Prestigious panels of experts have convened under
the auspices of such groups as the National Academy of Sciences (NAS), the Agency's Science
Advisory Board (SAB), and the Health Effects Institute (HEI). From these panels' deliberations
and reports of the NAS Committee on Research Priorities for Airborne Particulate Matter a
strategic research plan has emerged that will illuminate the path that leads to making the difficult
risk management decisions about regulating the sources of PM2.5.
As a part of the effort to carry out this PM research plan, the Agency issued a request for
applications (RFA) in 1999 to establish five PM Research Centers, to be funded at a level of
$8M in the first year of the Centers program. Each Center was to bring multi-disciplinary
-------
expertise to bear on important research questions identified in the RFA as of highest priority. As
a result of the competition that drew roughly 20 applications, the following PM Research
Centers were established:
a. Harvard University PM Center - Ambient Particle Health Effects: Exposure,
Susceptibility, and Mechanisms
b. New York University PM Center - Health Risks of PM Components
c. Northwest PM Center - Combustion-derived fine particulate composition,
exposures, and health effects
d. Rochester PM Center - Ultrafme Particles: Characterization, Health Effects, and
Pathophysiological Mechanisms
e. Southern California PM Center - Sources, Exposure, and Health Effects of
Particulate Matter
Roughly half of the five-year grant period for these Centers has passed, and the Agency
must soon make a policy decision on whether or not to continue the Centers program, possibly
through a second round of RFAs. The Agency has asked the SAB for its technical advice that
will inform this policy decision.
There are, of course, other alternatives to conducting research via a Centers-based
mechanism; e.g., awarding a large number of investigator-initiated grants. In order to evaluate
the relative merits of a Centers-based program versus other alternatives, it would be helpful to
have the research products from the current mechanism available to compare to the research
outputs from those alternatives. In this case, however, after only two and half years, the research
results from the Centers are just now beginning to appear in significant number in the scientific
literature, so it is too early to assess these outputs definitively in toto. At the same time,
sufficient experience has been gained from the Centers to date to allow a reasonable estimate of
the major strengths, weaknesses, and potential of the Centers-based mechanism as a means for
generating the kind of research results than will be needed by the Agency.
1.2 Charge to the Committee
Acknowledging the limitations inherent in this exercise, the SAB convened a group of
experts, whose knowledge and experience — individually and collectively — qualify them to
address the specific set of questions (the Charge) posed by the Agency.
Overall Question:
Is it likely that the PM Centers program will be sufficiently successful to merit
continuation in FY 2004 and beyond? In which areas, to what extent, and for
what reasons is a PM Centers program beneficial? Where it is not, what
improvements can be made?
Specific Questions:
1 .Recognizing the PM Centers program is barely at its halfway point, what important
research findings (or promising investigations) have been made that would not
-------
have occurred otherwise? What unique aspect(s) of a Centers program enabled
such actions to be taken.
2. To what extent has the direction or focus of research shifted as a result of the multi-
disciplinary interactions within the Center (i.e., findings in one department
influence researchers in another to change direction or emphasis). To what extent
have changes in research direction or emphasis been influenced by Science
Advisory Committee reviews, interactions with other PM Centers, or interactions
with the broader PM research community? Which factors have been most
influential?
3. How successful are Centers in communicating their findings to the public and
specifically, to those who directly use their research? Is it clear that the work has
been supported by the PM Centers program?
4. How, if at all, does a PM research centers program facilitate agreement or consensus
on protocols or procedures to enable more direct comparison of results among
research institutions or centers?
5. How, if at all, does a PM research centers program leverage or maximize use of
resources through sharing expensive equipment, samples, data, etc.?
6. How is the program perceived within and outside the research community? Does a
research center have greater visibility, and if so, what is the impact?
1.3 SAB Review Process
The PM Research Centers Interim Review Panel (Panel) was recruited following
nominations received from SAB Members and Consultants, the Agency, and the public. The
Panel met in public session on February 11-12, 2002 in Room 6013 of the EPA headquarters in
the Ariel Rios Building at 1200 Pennsylvania Ave. NW in Washington, DC. Written
contributions from the Panelists, prepared before the meeting, modified on the basis of
discussions at the meeting, and made available to the public, form the basis for this report. A
more detailed description of the SAB process for this review can be found in Appendix B.
1.4 Format of this Report
Following this Introduction, the report provides specific responses to the questions in the
Charge to the Committee (Chapter 3). Since a) the basis for the answers the Charge questions
are not totally independent and b) the responses to the questions were crafted by subgroups of
the Panel for subsequent consideration, editing, and adoption by the full Panel, a given point may
be repeated in several contexts throughout the report. However, the transmittal letter and a
summary of major findings and recommendations (Chapter 4) seek to focus more succinctly the
Panel's thoughts. A series of three appendices (a list of acronyms, a more detailed description of
the SAB process, and an abstract) completes the report.
-------
2. RESPONSE TO THE CHARGE
2.1 Overall Question
2.1.1 Is it likely that the PM Centers program will be sufficiently successful to merit
continuation beyond 2004?
The PM Centers Program a) has produced benefits beyond those normally found in
individual investigator-initiated grants, and b) is likely to continue to provide such benefits
throughout its current funding cycle. Overall, we find that the program merits continuation
beyond FY04 and suggest below areas in which its efforts can be enhanced.
The Centers have been and promise to continue being an important part of the PM
research portfolio of the Agency. At the same time, there are clear advantages to maintaining a
diverse research portfolio; e.g., by ensuring that the widest range of investigators are
contributing ideas to the PM program and by providing opportunities for cross-fertilization of
ideas between the PM Centers and other investigators at the Agency and in the greater research
community. Specifically, the Agency should continue to fund the other intramural and
extramural components of the overall PM research effort. Within that overall effort, maintaining
the PM Centers program in roughly the same proportion to the rest of the PM research program
will enable continued benefits to flow from the PM Centers program.
To take full advantage of the benefits and collaborations afforded by a Centers program,
continuation of the program should be based on a new, fully competitive RFA process, designed
in keeping with the opportunities for enhancements described below. The Centers program
should continue to be focused on addressing the PM issues relevant to the policy and regulatory
needs of the Agency, including the ability of the Centers to contribute to the replication of key
studies. Specific needs to which the Centers would be directed in a new round could include the
same topics (i.e., exposure and health) and/or new topics (e.g., source characterization and
assessment of emerging technologies). The areas should be defined by the Agency, based on
reviews of the priorities and accomplishments to date by the National Research Council (NRC)
Committee on Research Priorities for Airborne Particulate Matter and as part of an overall
assessment of progress to date and needs that are or are not being met by all elements of the
portfolio. The number of Centers to be funded should be developed within a flexible framework
and determined based on a) the availability of adequate resources to provide funding, per Center,
at a minimum comparable to that provided in current Centers, adjusted for inflation, and b) the
availability of high quality proposals which meet the test of intensive peer review.
2.1.2 In which areas, to what extent, and for what reasons is a PM Centers program
beneficial?
In its review, the Panel considered a wide range of activities underway at the individual
Centers, plus the results of initial efforts at integration across Centers. Drawing on its extensive
experience with the alternative to Centers-type grants — the individual investigator grants — the
-------
Panel identified several specific advantages that the Centers approach offered over these more
traditional mechanisms. These advantages include the following:
a. Enhanced flexibility and adaptability, leading to improved timeliness.
From the integrated Centers report reviewed by the Panel and presentations made at
the meeting, it appears that the time for hypothesis generation and experimental design has been
decreased and that hypotheses are being "vetted" through inter-Center communication before
laboratory studies have been actually begun. One example of this was the decision following
cross-Center collaboration to initiate relatively rapidly a subchronic animal exposure experiment
at the NYU center.
b. Continuity for five years, allowing longer term planning and research implementation.
In contrast to the normal project-specific grant, the Centers appear able to invest in
longer-term strategies on important questions; e.g., the systematic efforts by the Washington
Center to develop a biomarker for exposure to wood smoke and the detailed follow-up by the
Los Angeles Center of new exposure parameters for the Southern California Children's Health
Study (CHS).
c. Ability to pursue higher-risk and more difficult to finance efforts in methods
development, validation, and pilot studies, providing a greater potential for
innovation.
Efforts at methods development and validation often fare poorly in traditional
competitive grant programs, and yet they are essential to advancing the state of the science.
Centers offer the ability to undertake these efforts and, then, to field test them. In its review, the
Panel identified several such efforts; for example, the extensive inquiry at the Southern
California Center into quinones exposures and effects; the development through the Rochester
Center of new techniques for using CT scans in dosimetry; the development at the Northwest
Center of new particulate carbon personal sampling techniques; and the assessment of source
impacts and housing factors (ventilation) on effects estimates of the PM-hospital admissions
relationship from the NMMAPS study and the more detailed evaluation of the harvesting
phenomenon conducted by the Harvard Center.
d. Improved study designs, resulting from intra-Center multi-disciplinary integration.
The PM Centers program has allowed for the development of a critical mass in
interdisciplinary research at individual Centers. In concept, a Centers grant forces
interdisciplinary planning and coordination at the inception of study design, rather than as an
afterthought, thereby leveraging the value of interdisciplinary research as a whole. When
epidemiologists, exposure experts, aerosol scientists, toxicologists, physiologists, and other
scientists engage a problem collectively, there is a higher likelihood of a cohesive,
comprehensive approach to the research than when research is assembled from the ensemble of
-------
individually conducted research projects at the same institutions. Just two, among several,
successful examples of this interaction at the current PM Centers are
1) The integration of toxicology and epidemiology at the Harvard Center to
iteratively explore the connection between potential sensitive populations
and the cardiac effects of PM exposure.
2) The cross-disciplinary work among aerosol scientists, toxicologists,
epidemiologists, and exposure assessors to test the effects of mobile
source exposure at the Southern California Center.
e. Substantial potential benefits, resulting from inter-Center integration
Although the initial years of the PM Centers have been focused primarily, and
understandably, on the development of integrated programs within each Center, there is some
evidence of successful efforts to integrate research across Centers, especially following recent
efforts by the Agency to foster this collaboration through the development of the integrated
reporting for this review. Examples of these emerging benefits include the Rochester workshop
on investigation of cardiac effects across disciplines and the development of pooled analyses of
childhood effects in the Harvard 24 Cities Study and the Southern California CHS.
f. Demonstrated ability to "leverage" additional resources, resulting in an overall
enhancement in research of interest to the Agency
The existing and new studies funded by other organizations and by other Agency
programs presents an important benefit to EPA, leveraging its limited funds for PM research and
gaining access to the additional science generated on this broader scale. By providing a "critical
mass" of experience, interest, and expertise, a Center becomes attractive to outside funding
agencies as a credible source for generating answers to their questions in a cost-effective way.
Specifically, the breadth of PM health effects research at most of the Centers is significant and
appears to exceed substantially the $1.5 million/year contributed by the Agency's PM Center
program. Several Centers provide concrete examples where their programs have allowed them
to obtain additional funds; e.g. leveraging between the Northwest Center and the EPA
Cooperative Agreement exposure assessment study and the Harvard Center's use of data
collected by the Electric Power Research Institute (EPRI)-supported St. Louis bus study.
g. Other benefits, enhancing the value of the Centers Program
In addition to these larger benefits of the PM Centers Program, the Panel identified
several other specific benefits that appear to be emerging at different Centers, including the
following:
1) The ability to adapt and apply technologies/methods developed elsewhere to
the work within Center programs; e.g., the application of animal exposure
techniques for concentrated ambient particles from Michigan State
-------
University to the design of similar efforts at the Southern California
Center.
2) The attracting of established researchers in fields other than air pollution to
participate in air pollution studies; e.g. experience at the Rochester and the
Southern California Centers.
3) The thoughtful and carefully planned additional use of existing epidemiology
and other data bases for dose-response and other follow-up; e.g., the
Harvard Center follow-up of the Six Cities data set and of the NMMAPS
morbidity data set for dose-response. It is likely that this process first
began at the time that the original Center proposals were prepared. This is
is a particular benefit of the Center approach, since under a traditional
individual grant-based approach, it is unlikely that these additional
analyses would have been completed due to the time pressures on
investigators who are required to apply continually for additional funding.
In summary, it is clear that there are substantial benefits possible in a Centers Program
that complement and expand upon other approaches available to the Agency, both intramurally
and extramurally. Given this evidence, the Panel recommends that the program be continued in
a new round of Centers-concept funding, so long as adequate resources are maintained to ensure
the critical mass necessary to success within each Center. The Panel further suggests that this
Centers-based approach may be useful in other aspects of the Agency's program; e.g., the need to
develop approaches to study the air pollution mixture, not just its individual components.
2.1.3 What improvements can be made in the Centers Program?
Having concluded that the Centers Program merits continuation, the Panel identified
several ways in which a new round of Center grants could be enhanced, either by expanding
upon activities already underway or by undertaking new efforts. Importantly, the Panel noted
that while there are evident benefits of integration within and across Centers, there are also
challenges to insuring that the work of the Centers does not become isolated from that of other
researchers within the Agency and in the academic community. Several of the enhancements
suggested below aim to ensure this broader cross-fertilization of ideas.
Specifically, the Panel sees the following opportunities for continued benefits and
improvement:
a. A new RFA should seek answers to a clear set of priority research questions, based on
current assessments of the state of knowledge, including those from the NRC, and
the degree to which other PM investments (Agency intramural, as well as Agency
and other extramural) are already meeting those needs. This focused approach
was followed quite usefully in the first RFA and should be continued.
b. There should be systems established and resources available, from the start, for inter-
Center collaboration. The Panel noted that the request for an integrated summary
report of the Centers - which was prepared for this review — both documented
-------
current efforts and had the added benefit of substantially increasing cross-Center
communication and the identification of opportunities for integrated activities.
Future Centers could be encouraged to engage in this communication earlier,
perhaps with an Agency requirement for such reports on a regular basis.
c. As the PM Centers program matures, there is a need for a mechanism that could
provide overarching scientific advice and direction. Although the Panel was
hesitant to recommend another layer of formal oversight, it did feel that enhanced
advice and direction could be achieved, perhaps through incorporation of a
regular meeting of Chairs and/or participation of other "outside" representatives
of the Center Science Advisory Committees (SACs) into the annual Directors
meeting. This enhancement would
1) Provide opportunities for systematic comparison of results from across Centers
and beyond; e.g., exposures and effects of PM from different sources.
2) Enable identification of new opportunities for collaboration among Centers and
with the Agency and others in the research community.
c. To ensure that the Centers do not become isolated from the rest of the scientific
community, there is a need for regular opportunities — perhaps as a public part of
the annual Center Directors meetings — for interaction and cross-fertilization of
ideas with:
1) Agency intramural researchers
2) The large number of other PM researchers (STAR grants, other US funding
sources, Canada, Europe, etc.)
These activities could result in an additional benefit to EPA by providing a
mechanism for keeping abreast of the state of the science on PM issues.
d. It would be useful to see enhanced interaction between the research conducted at the
Centers and ongoing intensive air quality monitoring efforts, such as those at the
Agency's supersites and others. (The Southern California Center provides a
model of how this might be done. Interaction with NARSTO would provide other
opportunities.) The detailed air quality data collected at these sites should be
utilized as much as possible by the epidemiology community. In general, it will
be important for the various Centers to consider the chemical composition, as well
as size, of constituents of PM in their research designs.
e. There should be expansion and formalization of the current visiting scientists program
at some of the Centers in order to take advantage of the Centers as data, methods,
equipment, and subject information repositories where scientists could come to
focus on specific issues, while utilizing Center expertise and resources.
-------
With these opportunities for enhancement, the PM Centers Program should be able to
continue to contribute substantially to the overall Agency PM Research Program.
2.2 Specific Charge Questions
2.2.1 Results to-date
Q 1: Recognizing that the PM Centers program is barely at its halfway point,
what important research findings (or promising investigations) have been
made that would not have occurred otherwise ? What unique aspect(s) of
a Centers program enabled such actions to be taken?
Q2: To what extent has the direction or focus of research shifted as a result of the
multi-disciplinary interactions within the Center (i.e., findings in one
department influence researchers in another to change direction or
emphasis). To what extent have changes in research direction or
emphasis been influenced by Science Advisory Committee reviews,
interactions with other PM Centers, or interactions with the broader PM
research community? Which factors have been most influential?
The Panel determined that these two questions were at the core of its charge and,
therefore, spent the bulk of its effort having members with particular expertise (e.g., in
epidemiology, exposure assessment, monitoring and air chemistry, toxicology, science
management, etc.) review the Centers' progress, in depth, from the perspective of that expertise.
The results of these expertise-focused reviews are summarized in the subsections that follow
below and, in some cases, draw verbatim from material presented later in the report. A number
of views/themes are repeated in these different reviews and provide the basis for many of the
overall conclusions of the Panel generated in response to the overall charge question above (see
Section 3.1).
a. Epidemiology
The epidemiology studies in the Centers to date have been partly extensions of
ongoing studies, partly more detailed analyses of existing data bases, and partly new field or
panel studies, a reasonable approach given that a significant fraction of air pollution
epidemiology uses data collected for other purposes. The Centers program allows analysis of a
series of specific questions (e.g., on harvesting and threshold/non-threshold issues) that would be
difficult to fund using separate grants. Therefore, the Centers program is contributing to
efficient utilization of ongoing studies and existing databases. Although it is hard to judge
whether these analyses would not have been done without the Centers program, it seems clear
that results are now being produced more quickly.
A further advantage of the Centers funding mechanism is the flexibility and discretion
that it provides to the Principal Investigator (PI) over a five-year period to direct funds in
interesting directions without having to go through a 1+ year grant funding cycle before work
can commence. This flexibility results in a very significant potential, if utilized well, to
accelerate the development of research findings of policy relevance. It was nicely argued by one
-------
of the Center Directors, that, given the large amount of money (both on the benefits and cost
sides) which hinge on the regulatory decisions informed by the Centers research, there is a strong
societal imperative for maximum speed in the generation of policy-relevant research results. Of
the funding mechanisms available to EPA, the Centers approach appears to be the best
mechanism for achieving this speed.
Another value-added activity originating from the Centers Program is the very thoughtful
and carefully planned use of pre-existing data sets in follow-up analyses. It is likely that this
process first began at the time that the original Centers proposals were prepared, and it is a
particular benefit of the Centers approach that these follow-up analyses have now been
completed. Under a traditional individual grant-based approach, it is less likely that these
additional analyses would have been completed due to the time pressures on investigators to
continually apply for additional funding. A further example of this value-added activity is the
planned, pooled analysis of the Southern California CHS and the 24-Cities Study. While both
studies have evaluated lung function and lung function growth, the CHS was focused on the
impact of mobile sources, while the 24-Cities Study was focused on the acid aerosol/sulfate
Eastern air pollution mixture, thus offering the opportunity to compare health effects in areas
with substantially different air quality.
Another related advantage of a Centers-based approach is the ability to pursue lines of
pilot investigation which, due either to their exploratory nature or to their relatively small scale,
would not be easily fundable as stand-alone grants. The Centers mechanism has made it possible
to investigate a variety of important epidemiologic questions based on new analyses of existing
databases. Most, though not all, of the Centers have been very effective in exploiting these
unique advantages of nimbleness and flexibility in maximizing their investments in
epidemiologic work.
Have the Centers made a difference in the conduct of epidemiologic research? The
answer is clearly "Yes", in part, because investigators have been free to continue pursuing
promising leads without having to apply for new grants. They have been able to follow new
directions, that might not necessarily have obtained funding in a competitive process. Examples
include the following:
1. Center funding has allowed the Harvard Center to refine and explore alternative
methods, as well as the application of the methods to alternative data sets, in its
research on harvesting and threshold/exposure response. The preparation, review,
and awarding of proposals/contracts could have delayed the process significantly.
2. The Centers Program has enabled the Southern California Center to conduct extended
analyses of the CHS as new hypotheses are introduced.
3. The Centers mechanism enables researchers to quickly address a new subject; e.g., the
association between diabetes and PM pursued by the Harvard Center and the
study of the association between reproductive effects and air pollution planned by
the Southern California Center.
10
-------
4. The Centers Program enables researchers to replicate quickly studies in one
geographic area in different areas; e.g., activities at the Northwest Center.
Comparisons of results from similar studies in different geographic regions can
clearly provide insights into the underlying mechanisms.
5. The Centers are planning a workshop to discuss and harmonize source apportionment
methodology for use in epidemiological studies. Several epidemiological studies
have evaluated source category impacts. The workshop will attempt to utilize
more fully the available source appointment techniques and source signature data
to evaluate the health impacts of specific sources.
Given these strong advantages, there are several ways in which the work of Centers
might be further enhanced:
1. In view of the public health significance of long-term effects on survival, the effort
within and among the Centers to provide new insights is still somewhat limited. There has also
been relatively little work on the development of appropriate monitoring
strategies/methodologies (statistical designs, assessment of study design efficiency, sampling
method development) for long-term studies. Without these developments it is likely that
continued analysis of long-term impacts or the planning of future chronic effects studies will
remain opportunistic — relying primarily on existing data such as the AIRS data or possibly the
speciation network data. Although the budgets of the Centers seem large, those budgets are
necessarily divided into many pieces in order to achieve the multi-disciplinary character that is a
hallmark of the Centers. As a result, there is generally not a sufficiently large amount of money
available for mounting a de-novo, stand-alone epidemiology study, which can be quite
expensive.
Nonetheless, there are several examples of work underway in this important area. The
Harvard Six Cities Study follow-up has been updated, and there has been mention that the
Northwest Center might investigate another cohort. There are also two examples of ongoing or
completed studies on school children (the Southern California and Harvard Centers) that will use
sophisticated exposure assessment techniques.
In sum, it seems that the Centers program is ideally suited to exchange and harmonize
exposure assessment efforts in the long-term studies.
2. It is important to note there is another potential side to rapid implementation of
changes in research; i.e., a risk of poor quality if the peer review of interim research results and
decisions is sped up too much. It is clear that informal peer review occurs in the Centers via
their Science Advisory Committees (SACs). Continued attention to and enhancement of these
reviews by the SACs would help to ensure that the quality of research continues to be high and is
perceived to be so by the public.
3. It would be useful to see enhanced interaction between the research conducted at the
Centers and ongoing intensive air quality monitoring efforts, such as those at the Agency's
11
-------
supersites and others. (The Southern California Center provides a model of how this might be
done. Interaction with NARSTO would provide other opportunities.) The detailed air quality
data collected at these sites should be utilized as much as possible by the epidemiology
community. In general, it will be important for the various Centers to consider the chemical
composition, as well as size, of constituents of PM in their research designs.
b. Monitoring and Air Chemistry
There are several examples of research progress that has been made as part of the
Centers program that would have been unlikely to occur or would have been less beneficial to
the overall research effort in the absence of such a program.
One example is the planned workshop (described in the previous section) to discuss and
harmonize source apportionment methodology for use in epidemiological studies.
Many of the Centers are making use of concentrated ambient particles for toxicological
studies. The extent of integration of this methodology, including the detailed characterization of
particle speciation, has been thorough under the Centers program. There has been evidence of
an iterative process in which improved particle characterization from monitoring and
epidemiological field studies have informed toxicological studies. While it is premature to have
expected a second iterative step in which the results of these toxicological investigations have
contributed to the development of new epidemiological studies, such a positive feedback of
information can be anticipated in the future.
As a result of specific Center needs, there have been initial developments of new
sampling techniques and extensive integration of state-of-the-art existing measurement
techniques in epidemiological, toxicological, and exposure investigations. Examples of new
methods and their immediate and extensive use in Centers research are the use of the multi-
pollutant personal sampler (a device worn by participants to measure total personal exposure) in
several of the panel studies, the development of the ultrafine particle concentrator, the
development of new methods to measure methoxyphenols as markers of wood smoke
combustion, and the development of a new personal sampling method for temperature-resolved
carbon fractions.
Another interesting development that exemplifies the flexibility inherent in the Centers
program is the increased emphasis on spatial variability within the Southern California and
Northwest Centers. This new research direction builds upon studies conducted in Europe
investigating the impact of proximity to traffic sources and adds a potentially important new area
of emphasis for epidemiological studies which has not been considered in the time series studies
or the main US cohort studies.
Additional areas in which the Centers program has made contributions that would not
have been made otherwise include the following:
1. Validation studies
The Centers Program makes it possible to conduct specific short-term studies
12
-------
designed to validate or test methodology used in larger studies or to address specific research
questions that have arisen in larger studies. Even if such short-term studies were to be
contemplated under a more traditional investigator-initiated research program, they would be
unlikely to be supported. Examples of such validation studies include a) the assessment of
source impacts and housing factors (ventilation) on effects estimates of the PM-hospital
admissions relationship from the NMMAPS study and more detailed evaluation of the harvesting
phenomenon and b) the plan to replicate the multi-pollutant exposure sampling in an additional
location, beyond Baltimore where the initial investigation was performed
2. Pilot studies
Centers funding makes it more possible to design, develop, and test new
methodologies or to explore innovative hypotheses, activities which would likely be less
successful in an investigator-initiated grant environment. An example of this type of study is the
Southern California Center's work on quinones and other organic compounds that are precursors
to the development of reactive oxygen species. This effort has involved the development of new
sampling and analytical methods to link exposure assessment with toxicological investigations.
c. Exposure assessment
To date, exposure assessment activities have focused in four areas: 1) investigations of
the relationship between personal exposure to and ambient concentrations of PM; 2) resolving
the contributions to personal PM from indoor sources and infiltration from ambient particles into
indoor airspaces; 3) analysis of specific chemical components of personal PM that could explain
observed health effects; and 4) measurements of personal exposure to mixtures of PM and
gaseous pollutants. These research activities, as well as others at the PM Centers, are integrated
with research efforts in epidemiology, toxicology, etc., which is a major strength of the PM
Centers approach. Another strength is that the research, while generally integrated across
Centers, makes use of Center-specific environmental and lifestyle characteristics that may
provide further clues on exposure-response relationships. The recognition and exploitation of
these differences and similarities in a more integrated fashion is another strength of the PM
Centers.
The exposure research approaches and findings to date are not novel. Some
investigations have confirmed prior reports by non-Center investigators, and other investigations
have applied methods developed and used by non-Center investigators to their specific area.
Still others have used instrumentation developed by Center investigators prior to the
establishment of the centers. However, the advantage of exposure research at the Centers is that
the findings have immediacy in terms of feeding into health-related studies because of the multi-
disciplinary principles upon which the Centers undertake their research activities. Information
sharing and Center-specific internal cross-disciplinary interaction and coordination in exposure
research are obvious and very strong; e.g., the references to the NMMAPS and Baltimore studies
in the previous subsection.
The Centers program is clearly allowing the Centers to improve the exposure assessment
component of the epidemiology studies. It cannot be stressed enough that this is where
important new insights will emerge that will help policy makers eventually to identify which
13
-------
particle components, attributes, and sources are important in explaining the health effects seen in
epidemiologic studies. The benefits could still be greater if the Centers were to put more effort
into applying the same tools to all relevant particle exposure measurements; e.g., assess spatial
variability on the regional and local scale for secondary components, ultra-fine particles (UFP),
traffic-related components etc.
Each of the current Centers has a research project related to exposure of various
populations to environmental levels of PM and co-pollutants. At the same time, not all Centers
have as their primary goal conducting a large scale population study. This is probably a good
approach since the cost of such studies requires the diversion of significant Center resources.
However, these are important studies, and the cost of such studies may require funding by a
different mechanism (perhaps a cooperative agreement) in order to take advantage of resources
available from the Agency, the National Institute of Environmental Health Sciences (NIEHS),
the Centers for Diseases Control and Prevention (CDC), the National Institute of Heart, Lung,
and Blood Institute (NHLBI), and other national agencies.
The Centers program provides the opportunity for exposure scientists to share results and
hypotheses in forums that can effectively disseminate important ideas and results to members of
multiple disciplines as diverse as toxicology, epidemiology, and clinical sciences. The exposure
scientists provide the link between the epidemiology and toxicology studies with findings of
better indicators or metrics of exposure in populations at risk, which can augment or replace
specific PM components in toxicology evaluations; e.g organic carbon and ultrafine aerosols,
instead of elemental carbon and non-size segregated aerosols that were originally used to
examine mechanisms of exposure and response. For example, in the current Centers program
this integration is manifested by panel studies of exposure and health outcomes. Instead of
conducting a single RO1-based exposure panel study that would produce population exposure
intensities and profiles, the Centers provide the opportunity to augment the usefulness of these
measurements by integrating them with health outcomes research. In an RO1-based approach, a
new grant application targeted at health outcomes would probably have to be submitted based on
the results on the prior RO1 exposure study. Thus, to meet the needs of the national PM
research program, the Centers concept provides a more effective use of time and resources.
It is too early in the first funding cycle of the Centers to see clear examples of feedback
loops between exposure and health-related studies that change the direction of the investigation
in the various disciplines. At this time, the exposure assessment research efforts are guided by
the need to reduce uncertainty in specific areas of personal and community exposure to PM in
order to reduce uncertainties in health investigations. However, there are activities that may
result in redirection of health effects studies because of exposure research findings; e.g., the
finding of quinones and related compound concentration gradients.
It would seem that the exposure-related research undertaken to date, with very few
exceptions of still uncertain significance, would probably have been carried out without the
Centers. However, efficiencies in the timeliness of the research and the application of the results
are hallmarks of the Centers program and would be unlikely to be achieved otherwise. It is
important also to recognize that there is a very large body of research on exposure to PM outside
14
-------
the Centers. It is not clear that the Centers are as active in the incorporation of non-Center
research they are with intra- and inter-Center findings.
One approach to incorporating the non-Center findings would be for the PM Centers
program to organize an assessment of the state-of-exposure-science and related disciplines that
includes work being conducted both inside and outside of the Program. Such periodic
examinations would help the Centers in planning and conducting their research. There are other
programs in the US, Europe, and elsewhere that have and continue to accumulate information
and results that can assist in planning Centers-based activities and in the development of external
collaborations.
Finally, although PM characterization activities are described as being directed at
physical and chemical characteristics, most of the focus is on chemical composition size
distribution. There are some initiatives to look at other attributes, surface characteristics being a
particularly important one. The Centers program is uniquely positioned to provide a "whole
picture" evaluation of the exposure-effects continuum. This approach needs to be enhanced both
in the PM characterization/exposure end of the paradigm and in the integration of the
multiplicity of health effects to explain alterations in physiology that can lead to early death and
disease aggravation.
d. Toxicology
Among the most promising aspects of the PM Centers program is the focus on
understanding the biological plausibility and mechanisms, dosimetry, and further identification
of the toxic components of PM. Addressing these issues, in the context of how epidemiological,
exposure, aerosol, and other sciences are woven into the picture, increases the likelihood of
accurately assessing the plausibility of proposed hypotheses and mechanisms. Furthermore, the
collective presence of elite scientists within and across the Centers seems to promote a
considered and consistent approach to testing and validating hypotheses. The intra- and inter-
Center attention on new discoveries and findings appears to force higher quality of product. This
implied peer presence and peer review increases the level of confidence in results reported from
the Center studies as a whole.
The Centers, through a series of animal and human clinical experiments, have been
effective in evaluating hypotheses related to inflammation and immunity and cardiovascular
effects due to exposure to PM at ambient levels. The inflammation pathway has been linked to
both acute and chronic effects. In order to test and evaluate the validity of observed results,
multiple Centers collaborated, through controlled interactive experiments and shared protocols,
in testing, for example, the effects of different particle size fractions and conducting inter-species
comparisons. They have also begun addressing factors of susceptibility, such as aging. The
outcome of this research has been a remarkable consistency and continuity in the observed
effects that appear to lead to unified hypotheses on mechanisms and pathways. This weight-of-
evidence and the need for internal consistency in understanding the observed effects is a
significant contribution of the PM Centers.
15
-------
Ongoing and future efforts directed at further deciphering mechanisms for acute effects
appear promising and responsive to one of the critical challenges to the existing modifications to
the PM standard. In the future the Centers will likely address chronic and subchronic effects that
have previously been reported in epidemiological literature. Also, pilot studies are planned to
address dosimetry issues and hypotheses. Addressing most of these areas has required
significant innovation and employment of study designs and technologies that previously had not
been applied to these areas. Such innovation is another major attribute of a Center-based
program.
It appears that preparation for this review provided a significant stimulus for inter-Center
collaborations in developing and evaluating biological and toxicological hypotheses. During the
course of this review, the Panel learned that the Center Directors are mapping out meaningful
next steps for enhancing the collective understanding and interpretations of results reported to
date. Since PM and its components can have significant regional characteristics, it is important
for the Centers to consider exchange and further evaluations of the PM itself. The relevance of
PM composition and related source attribution are critical to our understanding of the reported
results.
Figure 1, taken from the presentation of one of the Center Directors, Dr. Oberdorster,
provides a unifying patho-physiological scheme for conceptualizing the mechanisms of PM
effects.
Biological Mechanisms ofERMg 1 From Exposure to Effects
Ambient Particles
(Pulmonary Deposition)
Epithelial Cell
Injury
Sensory
Nerves,
Ganglia
Extra-
pulmonary
Tissues
•Liver
•Bone-
Increased ROS
•Inflammation
•Allergy
Infectivity
Endothelial
Dysfunction
Cardiac & Respiratory Health Effects
16
-------
This integrative picture was developed through the collaborative discussions across the
Centers and has provided a roadmap for larger toxicology community; hence, it is a significant
contribution. The central role of oxidative stress is being investigated in all Centers as shown in
Figure 2, also taken from Dr. Oberdorster's presentation.
Figure 2
Examples of a Common Theme:
Oxidative Stress
Harvard; CAPs *• coronary events
New York; Transition metals on PM > infectivity
Northwest; PM ^-asthma aggravation
Rochester; UFP +-pulm. inflam. >endoth. dysf.; age
So.California; Quinones, ketones on PM *• release of ROS
Anot
her example of collaborative efforts that have been strengthened through the Centers is the rapid
initiation, development, and review of a protocol for subchronic CAPs exposure studies in mice,
subsequently leading to a chronic study. Such studies were not envisioned in the original RFA.
However, through inter-Center discussions and review, these studies were identified as critical to
furthering understanding of the mechanism of particle toxicity. The draft protocols have been
circulated for comment and refinement through the Center Directors, with the goal of optimizing
the protocol. The review process has included comments and suggestions from Agency
scientists as well, in keeping with the Centers' outreach to the scientific community.
e. Science Management
The Centers program has allowed for the development of a critical mass of technical
PM expertise in interdisciplinary research at and between the individual Centers. By design, the
Program forces interdisciplinary planning and coordination at the inception of study design,
rather than as an afterthought, thus leveraging the value of interdisciplinary research as a whole.
In concept, when epidemiologists, exposure experts, aerosol scientists, toxicologists,
physiologists, and other scientists engage a problem collectively, there is a higher likelihood of a
cohesive approach to the research than would result from a simple assemblage of individually
conducted research projects. One of the PM Centers' greatest successes to date is its serving as a
forcing function to promote this multi-disciplinary interaction from the ground up. In doing so,
the Centers program has created a network of scientific expertise that has the potential of
effecting a broad, balanced approach that also includes an imbedded mechanism of self-critical
peer-review.
17
-------
Judging from information in the integrated report from the Center Directors, another
attribute of the Center approach is that the time for hypothesis generation and experimental
design has been decreased, with the added advantage that hypotheses have been vetted before
actual laboratory studies have begun. While this aspect may not have played a major role in the
programs to date, the effect is likely to be greater in the future when several new and innovative
studies are envisioned.
An investment of approximately $1.5M/year/Center, while significant in total dollars,
should be viewed in the context of the types of studies necessary to advance this area. One panel
study of exposure/health alone can cost well over a $1M. If instead of using a Centers-based
approach, individual grants approach had been used, either 3-5 investigators would have been
forced to collaborate (always a technical and administrative challenge), or the Agency would
have had to establish and prescribe research area priorities over the five-year period; e.g.,
toxicology, first, and exposure studies, next. A research management approach, like the Centers
program, that has the capability of planning for both types of studies at the same time, holds the
promise of a superior outcome. In addition, this investment has been and will be advantageous
to the Agency because of the leveraging opportunities that arise from the Centers themselves, as
well as from other on-going research and support provided by other agencies and funding
organizations.
On the basis of reviewing the report from the Center Directors that was prepared for the
Panel, it would seem prudent to extend this program beyond FY04, to capitalize on the
investment made to date, and to take advantage of the apparent time efficiency that seems to be
demonstrated.
The request for the current SAB review seems to have motivated the type of inter-Center
collaboration and outreach that the Agency was hoping to achieve. This result argues for
instituting a requirement for an integrated annual report. It is important, however, that the
Center Program not become "an entitlement program" for certain institutions; rather, all
institutions should have to compete on their individual merits for continued funding beyond
FY04.
Based on the written background materials provided, there does appear to be some
disparity in the progress of individual Centers. Without an actual site visit and further
interactions with the individual Centers and their SACs, it is difficult to judge their individual
contributions and their progress relative to target. Such a site-specific examination is beyond the
scope of this particular review.
Because investigators at these particular Centers have a history of leadership in PM and
health effects research, their reputations were well-known prior to the Centers program.
However, the Centers concept has fostered additional development of a critical mass in
interdisciplinary research that has germinated new collaborations from others within the research
community, adding to the existing visibility and status of each of the Centers. As Centers, they
appear to render consistency to research in PM, which has generated additional confidence in the
results they report.
18
-------
There is a concern, however, that if research is conducted outside the Center framework,
then that work may be ignored or deemed to be less important, and consequently not as well
received. If their success were to lead to an attitude of exclusivity, then the Centers would run
the risk of becoming insular and oblivious to advances made elsewhere, some of which could
have implications to their own work. These concerns should be monitored, noting that some
extra-Center interactions can be promoted through such devices as symposia and workshops.
The Centers also provide excellent educational opportunities, allowing for the training of
young investigators in an atmosphere of interdisciplinary research. Those who are trained
outside and across the traditional disciplinary silos that have marked much of traditional training
and who are accustomed to collaborative research are more likely to transfer this understanding
to their future work. This birthing of a "next generation" of scientists is an important product of
the PM Centers Program that can potentially change the way research is conducted in the future
in all areas of environmental science.
The Centers have provided significant flexibility in which higher risk research activities,
such as method development, validation, and pilot studies can be accommodated. This
flexibility has led to the development of innovative methods, designs, and technologies. Inter-
Center transfers and sharing of personnel and technology have provided an added opportunity to
validate and test these innovations. These transfers have also extended to extra-Center
collaborations and have the potential for broader application. It is important to encourage and
further enhance this important attribute and contribution of the Centers program in the next
phase of the program. Some examples include the following:
1) New statistical methods for design of studies and analyses of results from
epidemiological and exposure studies.
2) Coarse, fine, and ultrafine mobile concentrators for field use.
3) Coarse, fine, and ultrafine biological sampling techniques for in vitro
mechanistic studies.
4) Inhalation toxicology trailers for field studies through the Los Angels Basin
(Human and animal trailers).
5) Particle instrumentation unit for field PM characterization.
/ Policy-Relevant Science
The fundamental reasons for initiating the PM Center research program sprang from the
science/policy debate that took place during the last review of the PM-NAAQS review and the
questions raised by the Clean Air Scientific Advisory Committee (CASAC) during its
deliberations. It was envisioned that an extensive research effort by the Agency would clarify
and resolve the issues, provide answers to questions raised, and assist in the next round of PM-
NAAQS review.
It appears that key areas of concerns that were expressed during the last review of PM-
NAAQS — in particular, dose-response relationships, existence or lack of threshold for PM
effects, and issues related to harvesting — that are central to future policy direction and
regulations, are being addressed by at least some parts of the PM Centers program, as well as by
19
-------
investigators outside the program. Because of the critical nature and implications for future
policy in these matters, it would be useful if these findings were replicated and validated by
other investigators, inside or outside the Centers programmer se.
There have been many projects started to address policy-relevant questions. At this
stage, the projects directly relevant to specific standard-setting questions have included
continuation and follow-up of studies underway prior to the establishment of the Centers
program; e.g., harvesting, dose response, follow-up of existing cohorts, some controlled human
exposure work, and experiments on underlying biological questions, such as mechanisms of
cardiac effects. The regular interaction within and between the Centers appears to have refined
these efforts. Although some portion of the work may have been possible with different funding
approaches, there have been clear benefits from the Centers-based approach, especially in the
toxicology and epidemiology interactions and its implications for the work on mechanisms.
The PM Centers research program has already produced some findings of policy
significance. For example, the addition of work from the Centers to other studies suggests the
absence of a threshold for PM effects, a finding which raises an important policy issue. Another
important observation is the suggestion by the Rochester Center that ultrafine PM has effects
distinct from those attributable to PM10 and/or PM2.5. Also, preliminary findings from the PM
Centers program support or expand upon previous findings that motor vehicle emissions appear
to contribute significantly to PM health effects, that NOx levels are associated with lung function
changes in children, and that the organic portion of PM may be responsible for some of the PM
effects. Such information raises some key policy and controls-related questions, such as how to
reduce exposure to the most toxic PM fractions.
Although there are substantial and innovative starts at examining individual PM sources
and components (e.g. ultra-fines, metals, and quinones) at different Centers, there is less
coherence in how the effects of exposures a) to emissions from different sources and b) to
different components and sizes of particles will be systematically compared, which is an
important forward-looking policy question. To date, although some consistent findings have
been reported, some intriguing findings that are not consistent between the Centers need to be
followed explored further. It will be critical for policy makers to understand the reasons for
these differences, if they are real. In addition, the Agency should take the lead in sorting out
these differences by working actively with the SACs and the Center Directors. In this regard, it
is worthwhile considering the option of creating an overarching mechanism to advise all of the
Centers and to coordinate insights in cases of seemingly conflicting data.
g. Multi-disciplinary and Inter-Center Integration
The STAR program is built upon the idea that the results must provide value-added to
the information that is being generated by the Agency, other stakeholders, and individual
investigators. It may be necessary to find metrics of success that go beyond scientific
publications derived from individual studies. The Centers' research impact value compared to
contributions generated via alternative funding mechanisms, will be an important barometer of
success. Again, the degree to which the Centers can provide answers to multi-disciplinary
issues, as well as provide key changes in direction, will be very important indications that the
20
-------
Center's program did make a difference. An important measure of success for this program is the
presentation of results and conclusions that will improve the scientific basis for the standard and
provide direction for implementation of control strategies by Agency program offices.
The Center Directors report prepared for this review reflect a good start at inter-Center
collaboration. It will likely take at least another year to assess the full impact of the anticipated
increases in interaction. Namely, will the intra- and inter-Centers interactions continue, leading
to better science or fuller consolidation of the science that has been learned? Such a relationship
will be a key metric of success. Will "Centered-ness" achieve new exploratory research that
continues along multi-disciplinary lines, or will the Centers consolidate their thinking to test a
single or a limited number of hypotheses? If the tendency is toward the latter, then the
effectiveness of the Centers approach may be lost, or the number of Centers could be reduced or
augmented to address new problems that would not be explored based upon the disciplines that
comprise the current individual Centers. In terms of other stakeholders, it is not clear that if the
way in which the Centers were established allows much flexibility for outreach to other
scientists, except at the individual investigator level. Fortunately, inter-organizational efforts are
usually most effectively started by individual investigators. The members of the Centers have a
history of success with inter-organizational collaborations, and their success over the course of
the next year may provide information about what kinds of formal outreach programs may be
required for a future RFA.
There is no clear path in the current design of the Centers program that integrates major
research findings into the development of an effective control strategy to protect public health.
A future RFA needs to clearly incorporate this important task to ensure that the results are
directed towards these concrete endpoints.
The previous RFA emphasized the need to a) set up a Center's clearinghouse function in
order to share of its research information with other entities and b) develop methods of
obtaining valuable information from other sources. These objectives should be a part of any
future RFA, and the current Centers need to be encouraged to move in that direction.
Two of the major attributes that should characterize the Centers are synergism and
broader exploration of the science, not necessarily premature consensus building among the
Centers. These concepts could be effectively developed through annual workshops organized by
the Centers. The workshop on cardiac effects conducted last year and the proposed workshop on
receptor modeling are examples of how a forward-thinking Centers program can move the entire
PM research field forward effectively.
2.2.2 Communications
Q3: How successful are Centers in communicating their findings to the public
and specifically, to those who directly use their research? Is it clear that
the work has been supported by the PM Centers program ?
21
-------
At this early stage, it is, understandably, difficult to judge how well the Centers have
succeeded in establishing effective communications. It is noteworthy that quite a few
publications have been generated to date that form a sound baseline for the direction of future
efforts in the Centers program and for research in the broader research community. Many of the
Centers appear to have used the popular media and community outreach effectively to publicize
their preliminary findings and to respond to inquiries. It also appears that they have assembled
multi-stakeholder SACs to ensure a flow of information in various sectors of the community.
It may be that with the infrastructure of the Centers the universities were better able to
feature this program as a community benefit, not singling out an individual investigator, but as
providing public health information to the media and public who have interests or questions
about PM issues. Since it is difficult to provide such a function in a cost-effective manner with
individual research grants, including this requirement in the RFA has reaped significant benefits.
It has also provided an administrative framework that could be utilized to broaden
communication activities to other groups; e.g. the regulated community.
One area in which there may be an opportunity for further improvement is the possibility
of a strategic communication plan across the Centers that would address the multiple audiences
that are targets for this information, including the scientific community. To date, Center-based
technical meetings have been planned with a year or so lag time, similar to what would happen
with individual investigator-focused grants. There may be advantages to thinking more broadly
about this problem, especially if the directions of the research continue and the findings from
these studies have the expected significant implications on public health. In this regard, making
the annual Centers meeting an open public scientific meeting would be especially valuable in
improving communication with the greater scientific community. To further enhance
communication, the Centers should maintain strong contacts with state and local air agencies
representatives, if that is not already the case.
2.2.3 Inter-Center interaction
Q4: How, if at all, does a PM research centers program facilitate agreement or
consensus on protocols or procedures to enable more direct comparison
of results among research institutions or centers?
There is evidence that the Centers appreciate the need for harmonization of protocols,
and there have been some attempts to do this. Achieving this end, however, is a daunting task
both organizationally and psychologically, since scientists like to adhere to their own pet
methods. If experiments are under way, then it is not a good idea to try and get workers to
change their protocols. However, for new studies or extensions of existing studies some
consideration of alternative, harmonized protocols could be advantageous. A centrally held
database of protocols would be an efficient and effective means of allowing experimenters to see
what protocols are in use or under consideration at other Centers. Periodic, joint meetings that
include discussion of methodology issues could also be undertaken.
22
-------
Probably the best example to date of inter-Center interaction is the Rochester Center's
workshop on the cardiovascular effects associated with air pollution: potential mechanisms and
methods of testing. The workshop culminated in an excellent report that contained a list of the
various methodologies recommended and the parameters they assessed. This effort could serve
as a model for workshops on other issues, such as particle size measurement, particle
composition measurement, in vitro toxicology models, and animal models.
There is a clear need for and benefit from increased inter-Center interaction, specifically
in the new panel studies being undertaken at all of the Centers. These studies mostly focus on
cardiovascular and respiratory endpoints and are generally of a small scale. There is much effort
in these studies to obtain detailed exposure data, as well as detailed health endpoint data as
described above. Such collaboration/interaction is an advantage both, in principle and - as
demonstrated in the Centers program— in fact. However, there is a potential problem with
statistical power and with generalizability arising from a collection of individual studies. Panel
studies limited to several hundreds of observations are susceptible to producing "noisy"
associations, which may vary from study to study or from study period to study period. Also,
because of the level of detail in the exposure and health endpoint assessments, there are many
associations to investigate, which increases the probability of chance associations, especially in
size-limited studies. The Centers program should stimulate and facilitate collaboration within
and between the five Centers, with the goal of harmonizing designs, methods of measurement,
and analysis of these studies. The foreseeable result would be a unified interpretation of the
results of the panel studies that would be much more rigorous than a post-hoc, meta-analysis of
completed studies would allow.
At the same time, it should be recalled that diversity of protocols can be seen as a
strength since huge amounts of data showing an effect using a single approach may not be as
powerful, or as persuasive, as decent amounts of data showing similar effects using different
approaches.
Among the more general opportunities for enhancing this cross-Center work are the
following:
a. The possible publication of a newsletter that would keep running lists of methods
being used and allow the Centers to identify areas of protocol exchange and
harmonization.
b. More PM Center workshops like the one organized by the Rochester Center where
methods can be exchanged and opportunities for protocol exchange and
harmonization can be identified.
23
-------
c. Attempts to develop reference materials, like the Southern California Centers efforts
on fine PM, which is an excellent idea when investigating a toxin so variable as
PM, especially for in vitro toxicology and animal studies.
d. Development of a centrally held, easily accessible database of downloadable pdf files
of protocols.
2.2.4 Leveraging
Q5: How, if at all, does a PM research centers program leverage or maximize use
of resources through sharing expensive equipment, samples, data, etc. ?
Each of the Centers — and each of the investigators within the Center — has specific
strengths in resources and expertise. There are two types of interaction that maximize resource
use: intra- and inter-Center interactions. There are many examples of intra-Center interaction;
e.g., common protocols and shared use of equipment across projects within a Center. One clear
example is the Rochester Center's common use of cardiac analysis, flow cytometers, particle
generation cores, and ultrafme concentrators across different studies.
There are also examples of specific strengths of one Center (e.g. sampling and analytical
tools and equipment) being made available to others through cross-Center collaboration. To
mention only three, the Harvard Center developed the concentrator that will be tested/used by
the Rochester Center, the Southern California Center has given PM samples to investigators at
other Centers, and the NYU Center is gaining input from other Centers as it prepares for testing
in mice.
In addition, the PM Centers are identified centers of PM expertise that allow them to
attract additional resources to fund other studies that are closely related to the goals of the PM
Centers Program.
However, there are still additional opportunities to enhance inter-Center utilization of
resources and expertise. Even though multi-disciplinary in nature, no Center can be equally
excellent in all areas. Such situations may not be even desirable, because it may not be an
efficient use of resources. It is important that the Centers recognize their individual areas of
strengths and make those available to others. This realization would increase cross-Center
collaborations in a significant way. Inter-Center collaboration is a difficult issue for inclusion in
a future RFA because each applicant develops his or her own independent research program.
There should be a mechanism (perhaps involving the SACs) to facilitate/insure synergistic cross-
linking among the personnel and hardware/software assets of the different Centers. This
coordinating effort must not interfere with the completion of the science proposed and developed
by each Center.
24
-------
2.2.5 Perception and visibility
Q6: How is the program perceived within and outside the research community?
Does a research center have greater visibility, and if so, what is the
impact?
As a novel approach for funding research, the PM Centers Program is being closely
watched on a number of fronts. The significant percentage of the Agency's total PM research
budget devoted to the Centers is additional motivation to observe the workings of the Centers
closely. Finally, the importance of the issue with which the Centers deal (i.e., the effects of PM
in our nation's air) insures considerable attention from a range of interested and affected parties.
Because each of these particular Centers has a history of leadership in PM and health
effects research, widespread knowledge of their work and their reputation preceded the Centers
Programmer se. However, the Centers concept has fostered the development of a critical mass
in interdisciplinary research that has spawned new collaborations from others within the research
community, adding to the existing visibility and status of each of the Centers. As Centers, they
appear to be maintaining the consistent quality in their research endeavors, which has generated
additional confidence in the results they report.
Beyond visibility in the scientific community, in general, the Centers Program has
provided excellent educational opportunities, allowing for the training of young investigators in
a non-traditional interdisciplinary manner. Such motivated young people, equipped with
technical skills and an appreciation of what it takes to attack a complex environmental problem
will be a valuable resource for the future.
One area for attention, however, may be that if research is conducted outside the Center
framework, it may be ignored or deemed to be less important, and consequently not as well
received. In their exclusivity, the Centers also would run the risk of becoming insular and
oblivious to advances made elsewhere, some of which may have implications to their own work.
These are issues that should be monitored and some extra-Center interactions can be promoted
through symposia and workshops.
25
-------
3. FINDINGS AND RECOMMENDATIONS
1. The PM Centers Program has both a) produced benefits beyond those normally found in
individual investigator-initiated grants and b) is likely to continue to provide such
benefits through to the end of its current funding cycle. Overall, the Panel found that the
program merits continuation beyond FY04 — through a new fully-competitive round of
applications — as one part of a diverse PM research portfolio at the Agency.
2. The Panel identified several specific advantages that the Centers approach offers over other
traditional research mechanisms, including enhanced flexibility and adaptability leading
to improved timeliness, ability to conduct higher-risk pilot and validation efforts, study
designs enhanced by intra-center multi-disciplinary integration, and improved leveraging
of the Agency's and the Centers' research resources, among others.
3. The Panel identified several ways in which a new round of Center grants could be enhanced,
either by expanding upon activities already underway or by undertaking new efforts.
Importantly, the Panel noted that while there are evident benefits of integration within
and across Centers, there are also potential challenges to insure that the work of the
Centers does not become isolated from that of other researchers within the Agency and in
the academic community. Key enhancements include the following:
a. Continued attention in a new request for applications (RFA) to focusing the
Centers' efforts on the most critical PM needs, as determined at that time
in reviews of research progress and needs by the National Research
Council and US EPA
b. The development of an informal, but overarching, mechanism of scientific
advice to the program
c. Enhanced opportunities for cross-fertilization of ideas with EPA intramural
researchers and the broader extramural community
d. Enhanced interaction between the research conducted at the Centers and
ongoing intensive air quality monitoring efforts, such as those at the
Agency's supersites and others
e. The provision of systems and resources from the start for inter-center
integration efforts.
26
-------
APPENDIX A - ACRONYMS
Agency
AIRS
CAA
CAAA
CAPs
CASAC
CDC
CHS
EPRI
FY
HEI
MMD
NAAQS
NAS
NCER
NHLBI
NIEHS
NMMAPS
NRC
ORD
PM
PM2.5
PM10
RFAs
RO1
SAB
SAC
STAR
UFP
US Environmental Protection Agency
Aerometric Information Retrieval System
Clean Air Act
Clean Air Act Amendments
Concentrated Ambient Particles
Clean Air Scientific Advisory Committee
Centers for Disease Control and Prevention
Children's Health Study (Southern California PM Research Center)
Electric Power Research Institute
Fiscal Year
Health Effects Institute
Mass median diameter
National Ambient Air Quality Standards
National Academy of Sciences
National Center for Environmental Research
National Heart, Blood, and Lung Institute
National Institute of Environmental Health Sciences
National Morbidity, Mortality, and Air Pollution Study
National Research Council
Office of Research and Development
Particulate Matter
Particulate Matter in the range of 2.5-10 micron
Particulate Matter of larger than 10 microns
Request for Applications
Single project research grants funded by the National Institutes of Health
USEPA Science Advisory Board
Science Advisory Committees (at each of the Centers)
Science to Achieve Results
Ultra-Fine Particles
A-l
-------
APPENDIX B
A MORE DETAILED DESCRIPTION OF THE SAB PROCESS
After receiving the Charge from the Agency in the summer of 2001, the SAB Staff
initiated a process for soliciting the names of candidates whose expertise would allow them to
make substantive contributions to answer the Charge questions. This solicitation included
a. Contacting various individuals within EPA
b. Publishing a notice in the Federal Register (Oct. 10, 2001, 51661-51662).
c. Contacting knowledgeable SAB Members and Consultants
The process (referred to as the WIDECAST) garnered 48 names, several being mentioned by
more than one source.
After further discussions with the SAB Staff and Agency personnel, the SAB Staff
Director contacted Mr. Daniel Greenbaum, President of the Health Effects Institutes who agreed
to serve as chair of the Panel. Having established Mr. Greenbaum's available dates to hold a
face-to-face public meeting, SAB Staff contacted all of the members on the WIDECAST and,
after briefly explaining about the SAB and the proposed interim review of the PM Centers,
inquired as to their interest and availability.
The 14 individuals who responded positively, submitting their public curriculum, became
the "Short List" of candidates. In each case, the person's curriculum vitae was used to construct
a "biosketch" of the candidate that described the individual's current position and affiliation,
expertise and experience in the matters at hand, experience on other advisory committees,
particular association with any of the PM Centers, and sources of research funding. The
biosketches were sent to the candidates for approval, after which they were posted on the SAB
Website (www.epa. gov/sab) for any comments that members of the public might want to make
that could help inform the final Panel selection. The SAB Staff Director made the final
selections, conferring with the Panel Chair and with the Executive Committee Chair (Dr.
William Glaze) . Primary consideration was given to expertise that the individual brought to the
Charge questions; specifically, areas of epidemiology, toxicology, exposure, science program
management, and policy-relevant science. An additional consideration was the benefit of having
some Panelists who were members of one or more the advisory committees associated with each
of the Centers. Such "inside insight" could be valuable to Panel as they grappled with how the
Centers "work" and what impact they have had or could have. One of the Panelists selected had
competed unsuccessfully in the Centers RFA competition, thereby bringing another perspective
to the Centers experience.
The 12-person Panel roster was announced on the SAB Website. In the days before the
meeting, complications arose for one of the members who had to withdraw; hence, the final
Panel of 11 Members (including the Chair).
Agency staff transmitted the review materials to the Panelists in late January, consisting
of the following:
B-l
-------
a. Charge to the Panel
b. "The EPA's Paniculate Patter (PM) Health Effects Research Centers Program",
prepared by the Directors and Senior Associates of the five PM Centers
c. Response to the Charges questions, prepared by each of the PM Centers
d. The Request for Applications (RFA) that announced the creation of PM Research
Centers Program
e. Information about Center-sponsored workshops
f. For each of the five Centers
1) Program Abstract
2) Progress Report
3) Publications List
On February 5, 2002 the Chair, Mr. Greenbaum, convened a conference call of the Panel
to discuss
a. The Charge
b. The review materials
c. Areas that the Agency and PM Center Directors should emphasize in their oral
presentations
d. Writing assignments (Lead and Associate Discussants) for the meeting.
e. Administrative matters
No public comments on the PM Centers were received prior to the meeting nor were any
presented at the meeting.
At the public meeting on February 11-12, 2002 in the SAB Conference Room (Ariel Rios
6013), the Agency presented some background material to set the context for the review. This
information was followed by presentations by each of the Center Directors, who were available
to answer additional questions, as needed during the course of the deliberation. Lead and
Associate Discussants used their written pre-meeting draft answers to the Charge questions to
initiate the discussion. They later modified these answers to reflect the sense of the entire Panel
as it emerged from the discussion. The Chair led the group in a collective discussion/editing of
the response to the Overall Question, drawing on material from each of the subsequent questions.
At the end of the meeting, the Chair summarized the answers to the Charge questions and the
major findings and recommendations.
Following the meeting, the Chair edited the draft generated by the Panel at the meeting.
After circulation and comment from the Panelists, the penultimate draft was discussed on a
conference call on March 27, 2002. The Panel-approved draft was sent to the SAB Executive
Committee (EC) for action during a publicly accessible conference call on May 8, 2002. [At the
meeting the Executive Committee approved the report, subject to final approval by designated
vettors,.. This report was forwarded to the Administrator on ....]
B-2
-------
APPENDIX C - ABSTRACT
The PM Centers Interim Review Panel (Panel) of the US EPA Science Advisory Board
(SAB) met on February 11-12, 2002 to review the Agency's PM Research Centers program as a
mechanism for generating research results that can inform Agency decision-making. Its major
findings and recommendations were as follows:
1. Overall, the Panel found that the program merits continuation beyond FY04 — through a new,
fully-competitive round of applications — as one part of a diverse PM research portfolio
at the Agency.
2. The Panel identified several specific advantages that the Centers approach offers over more
traditional research mechanisms, including enhanced flexibility and adaptability leading
to improved timeliness, ability to conduct higher-risk pilot and validation efforts, study
designs enhanced by intra-center multi-disciplinary integration, and improved leveraging
of the Agency's and the Centers' research resources.
3. The Panel identified several ways in which a new round of Center grants could be enhanced,
either by expanding upon activities already underway or by undertaking new efforts.
Importantly, the Panel noted that while there are evident benefits of integration within
and across Centers, there are also challenges to insure that the work of the Centers does
not become isolated from that of other researchers within the Agency and in the academic
community.
Keywords: Particulate matter, PM, research, Centers, US Environmental Protection Agency
C-l
------- |