December 13, 2016
EPA-HSRB-16-3
Thomas A. Burke, Ph.D., MPH
EPA Science Advisor
Office of the Science Advisor
1200 Pennsylvania Avenue, NW
Washington, DC 20460
Subject: October 19-20, 2016 EPA Human Studies Review Board Meeting Report
Dear Dr. Burke,
The United States Environmental Protection Agency (EPA or Agency) requested that the
Human Studies Review Board (HSRB) provide scientific and ethics reviews of two items: A
Protocol for Laboratory Evaluation of Mosquito Bite Protection from Permethrin-treated
Clothing for the U.S. Army After 0, 20 and/or 50 Washings; and a Completed Study for
Measurement of Potential Dermal and Inhalation Exposure During Manual Pouring of
Two Solid Formulations Containing an Antimicrobial. The Board's responses to the charge
questions and detailed rationale and recommendations are provided in the enclosed final meeting
report.
Signed,
Liza Dawson, PhD
Chair
EPA Human Studies Review Board
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INTRODUCTION
On October 19-20, 2016, the United States Environmental Protection Agency's (EPA or Agency)
Human Studies Review Board (HSRB or Board) met to address the scientific and ethical charge
questions related to two items: A Protocol for Laboratory Evaluation of Mosquito Bite
Protection from Permethrin-treated Clothing for the U.S. Army After 0, 20 and/or 50
Washings; and a Completed Study for Measurement of Potential Dermal and Inhalation
Exposure During Manual Pouring of Two Solid Formulations Containing an
Antimicrobial.
REVIEW PROCESS
The Board conducted a public meeting on October 19-20, 2016. Advance notice of the meeting
was published in the Federal Register as "Human Studies Review Board; Notification of a
Public Meetings" (EPA, 2016, pp. 68414).
Following welcoming remarks from Agency officials, the Board began its review of the first
item, A Protocol for Laboratory Evaluation of Mosquito Bite Protection from Permethrin-
treated Clothing for the U.S. Army After 0, 20 and/or 50 Washings.
The Board heard presentations from EPA for each agenda item in sequence, consisting of the
Agency's review of scientific and ethical aspects of the two studies. This Final Report of the
meeting describes the HSRB's discussion, recommendations, rationale and consensus in
response to each charge question for each of these items.
For each agenda item, Agency staff first presented their review of the science and the Board
asked the Agency presenters clarifying questions. The staff then described their review of the
ethical aspects and the Board asked clarifying questions about those. The HSRB solicited public
comments and next asked Agency staff to read the Charge Questions under consideration. The
Board discussed the science questions first and then the ethics question. The Chair then called for
a vote to confirm concurrence on a summary statement in response to each charge question.
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For their evaluation and discussion, the Board considered materials presented at the meeting, oral
comments, related materials and documents provided by the study sponsors, the Agency's
science and ethics reviews of the studies, oral responses from a study sponsor and protocol team,
and public comments made at the meeting.
CHARGE TO THE BOARD AND BOARD RESPONSE
Charge to the Board:
Is the protocol, "Laboratory evaluation of mosquito bite protection from permethrin-
treated clothing for the U.S. Army after 0, 20 and/or 50 washings" likely to generate
scientifically reliable data, useful for estimating the level of mosquito bite protection provided by
different textiles treated with permethrin?
Board Response:
The Board concludes that the research reported in the completed study is sufficiently sound,
from a scientific perspective, to be used to evaluate the bite protection level of permethrin-
treated military clothing within the limits of the number of washes tested. The Board also had
four specific recommendations for clarifications to be made in the study protocol, and additional
minor points which are described in the discussion below.
•	In the protocol, provide more clarity on formaldehyde, which was referenced in the
Safety Data Sheet for the permethrin treated fabric; specifically, please outline the source
of the formaldehyde and what level of residual formaldehyde, if any, would be expected
in the treated fabrics used in this study.
•	The Board recommends consistent washing of test subjects' arms before each exposure,
including the control test and first exposure, to improve consistency with regard to the
attractiveness of the volunteers for biting mosquitoes.
•	The Board requests clarification regarding the Invexus process for treating the fabrics
with permethrin. Specifically, the Board requests inclusion of data on the dermal transfer
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rate following the Invexus treatment, to support the calculations of MOE for the
volunteers in the study.
• The Board recommends clarifying whether the risk of anaphylaxis in the study is non-
negligible, and if in fact there is such a risk, providing appropriate training and
emergency measures such as Epi-Pens for use in cases of anaphylaxis; if the risk is
negligible, references to such may be deleted.
HSRB Detailed Recommendations and Rationale:
The HSRB discussed the design of the bite protection study, commenting that the study design
was sound and there were no major concerns about the methodology used in the study. It was
noted that the fabrics tested will be used in order of least concentrated to most concentrated
permethrin (untreated, then fabric washed 50 times, then 30 times, etc.) to avoid any potential
carryover of permethrin from one sleeve to the next. Bite-through data (representing the ability
of the mosquitoes to bite through the fabric to reach the subject's arm) from previous studies
informs the sample size calculations and feasibility of the present study. Laboratory raised
mosquitoes will be used for safety and consistency of results.
The Board commented that it is reasonable to conclude that the hazard presented by permethrin
in this study is low, as it has been tested extensively in animals and shown to have a low toxic
potency by all exposure routes. It does not appear to present an appreciable risk of dermal
sensitization. It is also reasonable to conclude that the exposure of subjects to permethrin in this
study will not be associated with an appreciable increase in risk of toxicity. In the extreme (and
unlikely) scenario of 100% of the permethrin in the unwashed fabric being absorbed by a 70kg
subject, the internalized dose would still be hundreds-fold less than the dermal NOAEL in rats.
MOEs in garment workers also support a high margin of "safety buffer" in exposure levels in
this study.
The Board recommended specifying the use of non-prescription hydrocortisone in the protocol
to relieve itching of mosquito bites, to distinguish this from treatment that could be interpreted as
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providing medical care in the study lab. Also, the language of the protocol mentions anaphylaxis
in the context of initiating a 911 call. If the likelihood of anaphylaxis is negligible, then perhaps
this reference should be deleted. If the possibility of anaphylaxis is not negligible, then
emergency treatment, such as use of an EpiPen from appropriately first-aid-trained staff should
be made available. The HSRB recommends that this issue be clarified in the protocol.
Comments on statistical aspects of the study
The study design using each subject as his/her own control is appropriate for removing variation
arising from differences in attractiveness of subjects to the mosquitoes. The factorial structure
(fabric x washings x species) is appropriate for comparisons of fabric type-number of washings
combinations within and across mosquito species. In addition, this design helps minimize the
number of subjects required for the study. The assumption of a binomial distribution for the
proportion of bites is reasonable if mosquitoes bite independently of each other. During
discussion with EPA staff, it was clarified that mosquito biting behavior should not be influenced
by behavior of other mosquitoes nearby—in other words, that independence is a reasonable
assumption.
Under the binomial assumption, the use of a generalized linear mixed model with a log link, and
subjects as a random effect, is the appropriate model for analyzing the study data. Calculation
of the required sample sizes using the assumed generalized linear mixed model is appropriate.
The simulation study to obtain the sample sizes was properly designed with the assumptions
clearly stated.
The statistics discussant for the Board also commented that it is unclear why the sample size for
the study reported in Attachment 2 included the generalized linear model with subjects fixed and
the generalized estimating equation (GEE) approach. Neither appeared to be considered or used
in the final protocol. In addition, both the fixed subject model and GEE could have been
analyzed using the same GLIMMIX procedure that was used for the random subjects model
instead of using GENMOD.
Overall the statistical design, sample size calculations, and proposed data analysis were clearly
explained and appropriate.
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Testing of mosquito species to ensure that they are disease-free.
There was considerable discussion by the Board regarding the question of testing of the
laboratory reared mosquitoes for pathogens. There were several questions raised. First, if there
is a real risk of pathogens being transmitted by mosquitoes then a full panel of testing would be
required to certify that they are disease-free; however, the proposed testing only incorporated
two tests and other pathogens would not be subject to screening. On the other hand, if the
laboratory-reared mosquitoes had virtually no possibility of exposure to pathogens then the
screening would not only be unnecessary, but could send a false signal about risks of the study or
exposure to laboratory raised mosquitoes in general. After extensive discussion the Board
agreed that testing for pathogens encountered in wild mosquito populations might not make
sense for laboratory reared populations. However, the Board also commented that some kind of
certification of the quality and safety of the mosquito population from a laboratory supplier is
needed, given that this is important for scientific reasons and for the safety of the human subjects
in the study. There was some uncertainty about what kind of quality measures should be used.
Chain of custody from lab to research team seemed to be an appropriate step, and perhaps US
Department of Agriculture (USDA) permits for shipping, if required, could also indicate
compliance with relevant security measures. The Board requested that the sponsor and EPA
determine the best method for certifying that the mosquito populations used in the study will be
safe and free of pathogens, and that these measures be included in the protocol document and the
informed consent. The discussion of these issues was carried over from the scientific review to
the ethics review of the study, given that the principal concern is with regard to risk to human
subjects.
Questions about the Invexus™ process
The protocol document references the Invexus™ process for treating the fabrics with permethrin,
which is a technology used to treat surfaces and materials such as textiles with various products
like antimicrobials. No data were provided regarding the efficiency or durability of this process,
or the amount of dermal transfer that might potentially be involved in the use of these treated
fabrics. Previous studies of pesticide treated fabrics that the HSRB reviewed in past meetings
had used other processes for incorporating the chemical into the fabric. Questions were raised
about whether the dermal transfer was likely to be the same, or more or less than, previous
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methods. EPA staff responded that the concentration of permethrin in the treated fabrics is the
same as in previous applications, but that they did not have data on the rate of dermal transfer for
the Invexus™ treated materials. The sponsor commented that they would provide those data as
part of the application to the EPA for approval of these products. The sponsor also indicated that
use of the Invexus™ process for other applications such as bed nets resulted in lower dermal
transfers than previously used methodologies for fabric treatment. The estimate for dermal
transfer used to calculate the MOE in this case was 15%, which in fact is a high estimate,
according to EPA staff, since data from previous studies using treated uniforms showed about a
10-fold lower transfer rate.
The Board acknowledged that the estimated dermal transfer rate was probably higher than the
actual rate, based on previous data, and requested that information about the transfer rate from
these Invexus™-treated materials also be provided in the protocol document.
Ethics
Charge to the Board:
Is the research likely to meet the applicable requirements of 40 CFR Part 26, Subparts K and L?
Board Response
The Board concluded that the available information supports a determination that the research
will be conducted in substantial compliance with 40 CFR Part 26, Subparts K and L, pending the
following three changes:
•	The protocol document should clearly specify that any protocol changes must receive
IRB approval prior to implementation, with the exception of changes needed to
eliminate apparent immediate hazards to human subjects.
•	The Board recommends deleting the Spanish language recruitment materials from the
study plan, as Spanish language informed consent and study implementation
materials will not be provided. Therefore, recruitment of individuals who speak only
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Spanish will not be feasible. Recruitment materials in English will reflect the study
population of English speakers included in the study.
• As mentioned in the scientific review, appropriate documentation should be provided
in the protocol and the informed consent document that the laboratory-reared
mosquitoes are free of pathogens and pose no risk of disease to human subjects.
HSRB Detailed Recommendations and Rationale:
The Board discussed the ethical aspects of the study that had been thoroughly reviewed and
presented by EPA staff. The Board agreed with EPA's assessment that the study was carefully
designed, that risks to human subjects were minimized, and that the informed consent process
was appropriate, and that the study presented an opportunity to learn valuable scientific
information which could be useful in the future for protection of military personnel.
Need for clarity on IRB approval of protocol revisions
The Board recommended clarifying in the protocol document that all protocol revisions must be
reviewed and approved by the overseeing IRB prior to implementation in the study. The current
wording in the protocol appeared unclear, and hence rephrasing for clarity is recommended.
Question of representativeness of the study population
The issue of Spanish language recruitment materials generated considerable discussion among
Board members. EPA staff commented that they supported the idea of using Spanish language
materials to recruit a more diverse study population for the study, with the aim of increasing the
representation of demographic and ethnic groups that are members of the military, the ultimate
users of the products being tested. Members of the Board commented that using Spanish
language materials without allowing for translation of all informed consent documents and
providing Spanish-speaking study staff would not likely contribute to diversity since ultimately
only study subjects who could understand English would be included in the study. These points
also led to broader discussion about whether it essential to obtain a study population that
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represented the full diversity of the US military. The Board ultimately agreed that due to the
relatively small size of the study, combined with the fact that each person serves as their own
control (thus eliminating worries about differences between individuals in susceptibility to
mosquitoes), this provides some rationale for not requiring inclusion of non-English speakers in
the study for scientific reasons. Furthermore, because the study offers no direct benefits to
subjects, the Board agreed that it was equitable to include only English speakers in the study;
potential participants would not be denied benefits of any type by their exclusion. Therefore, the
Board recommended that for the sake of logical consistency and efficiency it is best to eliminate
the Spanish language recruitment and focus solely on English-speaking participants.
Concerns about documenting safety of laboratory reared mosquitoes
Concerns about testing of mosquitoes for potential pathogens was raised during the scientific
review. As mentioned above, the Board agreed that some kind of certification that mosquitoes
are disease-free and are safely transported from laboratory to study site is required. The Board
stated that these measures are necessary not only for safety of human subjects in the study but
also for reasons of public trust. It is critical to document safety of interventions at each step so
that study subjects, oversight bodies and members of the public are assured that there are no
pathogen risks to human subjects through the testing procedure.
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HSRB review of A Completed Study for Measurement of Potential Dermal and Inhalation
Exposure During Manual Pouring of Two Solid Formulations Containing an Antimicrobial
Science Charge to the Board
Is the research in study AEA07 likely to generate scientifically reliable data, useful for assessing
the exposure of occupational workers and consumers who manually pour or scoop solid
formulation antimicrobials products?
Board Response:
The Board concluded that research in study AEA07 is likely to generate scientifically reliable
data, useful for assessing the exposure of occupational workers and consumers who manually
pour or scoop solid formulation antimicrobial products.
HSRB Detailed Recommendations and Rationale
The Board agrees with the EPA's review of the completed report finding that the AEATF II
addressed all issues identified during EPA and HSRB reviews of the study protocol and that the
research team was faithful to the final protocol when carrying out the study. The protocol design
and the careful execution of the study produced high quality data for exposure to powder and
granular formulations during product pouring events for both commercial and consumer
applications.
Given the wide range in the amount of product handled and the quality of exposure
measurements (inhalation and surrogate dermal), the data was well suited for evaluating the
relationship between the amount of product handled and exposure, particularly for water soluble
particles of 100% active ingredient. The results for each scenario (consumer, commercial,
powder, granule) and each exposure route (inhalation, long-long-dermal, short-short-dermal,
etc.) satisfied or nearly satisfied all the data quality objectives resulting in good confidence in the
statistics (average, median and 95th percentile) for exposure.
By extension, the results for the calculated unit exposure (UE) (i.e., exposures normalized to
pounds active ingredient handled) for the most part also satisfied the data quality objectives.
However, the UE results are not as generalizable as they could have been because, in this case,
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the amount of active ingredient handled (AaiH) was the same as the amount of product handled
(i.e., the material was prepared with -100% active ingredient) and in the opinion of the Board,
the composition of the powders and granules were not necessarily representative of other
formulations. The Board was not given any information about what typical composition of solid
pour formulations are, but if there are products with less than 100% a.i., then the UE calculated
by the Agency would not necessarily be appropriate as is.
The Board agrees that the deviations and amendments (both recorded and identified by the
Agency review) should not have impacted the quality and relevance of the data. One deviation
that was identified during the Agency review was that subjects were to carry out the task as they
normally would (AEA07 page 16), but the observer for ME14 gave a suggestion to not toss the
powder across the pool. This suggestion likely modified the behavior of the subject. It is difficult
to know what impact the modified behavior had on the outcome. There is no direct evidence that
can be used to make an assessment of what the outcome would have been if the behavior had not
been modified. The results for this individual, ME14, were at the high end of the distribution
(second highest) even with the potential behavior modification, but could possibly have been
higher if not modified. An analysis could be done to estimate what difference it would make to
the statistics if the true exposure for this individual had been higher or lower.
The other unrecorded deviation as noted in the Agency review was the order of activities where
the original protocol indicated randomly selecting the order of scenarios, but the final protocol
and actual study always had the granule pour first followed by the powder pour. This likely had
two impacts on the outcome of the study. First, for the less experienced subjects, conducting the
granule pour may have provided an opportunity to "learn" the activity such that the subsequent
ME would have produced exposures that were biased lower. It would be difficult to assign a
numerical value to this learning effect, but given the range of product handled and the range of
"experience" represented, the effect was probably small. The other possible effect of always
doing the granule pour first is that there was residue or carry over between ME for the same
individual (not much time elapsed between events). The protocol included measurement of the
residue (pre-exposure air sampling page 69) before each event, which was helpful in assessing
the potential contribution of carryover from one event to the next. The measurements showed
that there was carryover and that the highest carryover was associated with events that had large
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amounts of product handled. The background measured was up to several mg/m3. The Task
Force dismissed this contribution as, on average, being low relative to the average exposure
during a ME (33 - 42 mg/m3), but did not assess the percent contribution in paired analysis, i.e,
from one high granule event to a second low powder event. The carryover will bias all powder
samples upwards but the amount of bias is probably insignificant for most (but not all) of the
powder MEs. The ultimate effect would need to be assessed statistically but likely would bias the
low end of the distribution upwards (i.e., higher exposure) with no effect on the high end of the
distribution.
Both the AHEATF (the task force) and the EPA review highlighted several outliers in the data.
Ultimately these outliers were not removed from the data set, which is the correct approach, in
the Board's opinion, given that these MEs were real observed events. Apparent statistical outliers
are probably a result of the "purposeful diversity" approach used in these studies and the
presence of the occasional outlier (as long as it is not related to a bad measurement) likely speak
to the success of this approach in capturing the range of possible outcomes without actually
conducting a fully stratified sampling design. So it is important not to exclude apparent outliers
unless it can be linked to some other failure in the experimental design or measurement/analysis.
The Agency review identified limitations in the data and the Board generally agrees with the
Agency's conclusions, with the exception of concerns about lack of a conceptual model as
described below. The Agency mentioned the lack of representativeness caused by recruiting in
one area and during one season, noting that this could lead to the subjects not being
representative of the region as a whole.
Another limitation of the single location/season testing noted here is the lack of range in
temperature. Intuitively the mild temperature during testing could bias the results lower,
particularly for the water-soluble powders and granules (mostly for powders) because sweat
moistened skin will likely have a much higher adherence factor for airborne particles than dry
skin. This may be a non-issue depending on the characteristics of the cotton dosimeter because
the "stickiness" of the simulated dermal surface (i.e., cotton) may already be equivalent to moist
skin but that information has not been provided to the Board and was not known at the time of
review. The Board noted that there may be limitations with the use of these dosimeters for the
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measurement of exposure to solid residues, as there may be fall-off mechanisms that may
underestimate total exposure. The adherence dynamics of fabric may not entirely represent
adherence to human skin during the exposure event. In addition, during measurement activities
for the determination of solid loading on skin (i.e., exposure) fall-off of solid particles may occur
that result in an underestimate of exposure. These activities may include: subject walks to the
changing room, removal of dosimeters, placement of dosimeters in hangers, and partitioning of
dosimeters into pieces before placement in bags for analysis. The report did not describe any
specific measures to reduce fall-off during these procedures.
The biggest limitation in the data is the lack of generalizability of the surrogate test substance to
other solid pour granules and powder formulations. The final results do not provide a way to
assess the relationship between exposure and AaiH. The results do provide an excellent data set
for assessing the relationship between exposure and the amount of product handled because the
surrogate test substance made up 100% of the product. To relate this data to AaiH, a number of
important assumptions would need to be made about exposure pathways (direct contact,
splashing, resuspension/deposition, resuspension/transport/inhalation) and the pathways may in
fact be significantly influenced by the properties of the material itself, for example clumping
issues, fine particle plumes, high water solubility leading to 100% adherence to wet skin, etc. It
may be that "solid pour powders and granules" are always made of 100% a.i. and always are
highly water soluble (sticking to wet surfaces) but that information was not available for this
review.
Although the protocol and field study are scientifically reliable, what is missing from the EPA's
analysis is a conceptual model showing all reasonable exposure pathways for each of the primary
exposure routes (inhalation, dermal contact, indirect ingestion). A conceptual model, for
example, presented as a logic model type diagram, would facilitate further planning and research
about the appropriateness of the assumption of "proportionality." These diagrams, once
constructed, can be used in conjunction with ongoing research to help illuminate factors that
influence variance in exposure outcomes and, in this case, could help point to specific exposure
pathways that may or may not follow the assumption of proportionality (and why). For example,
a clump of material causing a splash will almost certainly reduce exposure by the "plume
pathway" but increase exposure by the "splash pathway" but, depending on the size of the clump
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will likely reduce the UE because a significant amount of product was transferred to the water
without contributing to resuspension (plume). Further conceptual modeling of exposure
pathways and factors influencing each of the pathways will enhance the design of research
conducted on exposures, and ultimately result in better science.
Statistical comments
The study design is appropriate and the sample size is adequate. The representativeness of all
Ohio users appears to be a limitation and could be factored into in a future study. The primary
statistical approaches are summary statistics and linear regression models with log transformed
exposure and pounds of active ingredients handled. Criteria forjudging a scenario are in terms of
a 3-fold relative accuracy and confidence interval width at most 1.4. The additional analyses
regarding outliers and non-detect are appropriate. Alternative statistical approaches including
quantile regression and log-log-logistic models are interesting. However, the linear regression
model with transformed variables is simpler and is also acceptable. Overall, the study design
and statistical methods used for data analysis are appropriate and acceptable.
Ethics
Charge to the Board:
Does available information support a determination that study AEA07 was conducted in
substantial compliance with Subparts K and L of 40 CFR Part 26?
Board Response
The Board concludes that available information supports a determination that the study was
conducted in substantial compliance with Subparts K and L of 40 CFR Part 26. The Board also
recommends several measures to improve ethical standards in future studies:
• The Board recommends that EPA communicate to the overseeing IRB that an
inappropriate amendment was approved in one of the protocol revisions for AEA07,
specifically, a change that deleted the statement that changes to the protocol would be
approved by the IRB prior to implementation. The Board recommends that the IRB and
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the study team be informed that implementing protocol changes prior to IRB review and
approval represents a violation of federal regulatory standards as well as a violation of
ethical norms.
•	The Board recommends updating AEATF II Standard Operating Procedures (SOPs) to
provide guidance for evaluating study-related adverse events (AEs), in particular for
determining whether events are likely related or unrelated to study participation. The
Board also recommends developing guidance for investigators on gathering relevant
medical information for evaluation of AEs through requests for access to participant
medical records and other activities to acquire appropriate medical information, as
needed.
•	The Board recommends that future protocols require that medical professionals
evaluating whether AEs are related to study participation be independent of the study
team.
HSRB Detailed Recommendations and Rationale
The Board agreed with the ethics assessment provided by EPA staff, that the study was
conducted in substantial compliance with regulatory standards at Subparts K and L of 40 CFR
Part 26.
However, there were four ethical concerns raised by the HSRB. First, there were apparently a
large number of protocol changes implemented without IRB approval. Most of the changes
related to logistical matters, for example, changing the sizes of product containers used for
pouring, and allowing for a longer time period for extraction of samples during laboratory
analysis. While these changes did not result in increased risks to human subjects, they represent
a violation of regulatory standards and norms of research oversight. In study AEA07, in many
cases IRB approval was sought after changes were implemented, rather than before. The Board
recommended that the study team and the reviewing IRBs be reminded that all protocol changes
must be reviewed and approved prior to implementation by the study team, except when
needed to eliminate apparent immediate hazards to human subjects.
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Also, during one of the protocol revisions, language in the protocol that originally stated
"Changes to the protocol currently require review and approval by the IRB prior to
implementation" was changed, deleting the phrase "prior to implementation." This change
underscored the failure to adhere to appropriate compliance measures with regard to IRB
oversight. EPA staff have already communicated to the study team and the IRB that this
language does not reflect ethical and regulatory standards, and the HSRB is in agreement with
the Agency's approach.
The third issue discussed by the Board was the response to adverse events. During the conduct
of the study, one of the study subjects experienced an AE that was determined by the study team
to likely to be unrelated to the study, since the symptoms (nausea and vomiting) were unrelated
to potential cyanuric acid exposure during the scripted pouring scenarios. However, there were
several gaps in the procedures for responding to an AE. Because the subject in this case was
taken to the emergency room for treatment, study staff needed a procedure to obtain information
about the medical assessment by ER personnel. Due to HIPAA requirements, it was not obvious
to study staff how to obtain relevant records. Procedures should be put in place to request that
subjects authorize the study team to access medical records in case of a suspected AE, so that
appropriate follow up and evaluation of the AE can be initiated if needed. In the particular case
in question, the subject also should have been instructed to call the hotline provided by the
chemical manufacturer for reporting potential exposures.
Fourth, the Board recommends ensuring that in all cases the medical provider or first responder
who is called to assist or help evaluate an AE be independent of the study team.
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US ENVIRONMENTAL PROTECTION AGENCY
HUMAN STUDIES REVIEW BOARD
Chair
Liza Dawson, Ph.D., Research Ethics Team Leader, Division of AIDS National Institutes of
Health (NIH), National Institute of Allergy and Infectious Disease (NIAID), Bethesda, MD
Vice Chair
Edward Gbur, Jr., Ph.D., Professor, Agricultural Statistics Laboratory, University of Arkansas,
Fayetteville, AR
Members
Jennifer M. Cavallari, Sc.D., C.I.H., Assistant Professor, Division of Occupational and
Environmental Medicine, Department of Community Medicine, University of Connecticut
Health Center
Farmington, CT
Gary L. Chadwick, Pharm.D., M.P.H., C.I.P., Senior Consultant, HRP Consulting Group, Inc.
Fairport, NY
Alesia C. Ferguson, MS., MPH., PhD., Associate Professor, Department of Environmental and
Occupational Health, College of Public Health, University of Arkansas Medical Sciences,
Little Rock, AR
George Fernandez, Ph.D., Statistical Training Specialist, SAS Institute, Statistical Training and
Technical Services, Sparks, NV
Kyle L. Galbraith, Ph.D., Research Integrity Officer, University of Illinois at Urbana-Champaign
Office of the Vice Chancellor for Research, Champaign, IL
Jewell H. Halanych, M.D., Assistant Professor, Internal Medicine Residency Program,
Montgomery Regional Campus, University of Alabama at Birmingham, Montgomery, AL
Walter Thomas Klimecki, D.V.M., Ph.D., Associate Professor and Department Head (Interim),
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona,
Tucson, AZ
Randy Maddalena, Ph.D., Physical Research Scientist, Indoor Environment, Lawrence Berkeley
National Laboratory, Berkeley, CA
Suzanne M. Rivera, Ph.D., M.S.W., Vice President for Research and Technology Management,
Case Western University, Cleveland, OH
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Jun Zhu, Ph.D., Professor of Statistics and of Entomology, Department of Statistics, University
of Wisconsin - Madison, Madison, WI
Consultant to the Board:
Kendra L. Lawrence, Ph.D., BCE, PMP, Health Sciences Product Manager, US Army Medical
Materiel Development Activity, Ft. Detrick, MD
Human Studies Review Board Staff
Jim Downing, Executive Director, Human Studies Review Board Staff, Office of the Science
Advisor, United States Environmental Protection Agency, Washington, DC
NOTICE
This report has been written as part of the activities of the EPA Human Studies Review Board, a
Federal advisory committee providing advice, information and recommendations on issues
related to scientific and ethical aspects of human subjects research. This report has not been
reviewed for approval by the Agency and, hence, the contents of this report do not necessarily
represent the view and policies of the Environmental Protection Agency, nor of other agencies in
the Executive Branch of the Federal government, nor does the mention of trade names or
commercial products constitute a recommendation for use.
In preparing this document, the Board carefully considered all information provided and
presented by the Agency presenters, as well as information presented by public commenters.
This document addresses the information provided and presented within the structure of the
charge by the Agency.
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