December 10, 2007

Minutes of the

United States Environmental Protection Agency (EPA) 

Human Studies Review Board (HSRB) 

November 13, 2007 Public Teleconference Meeting

Docket Number: EPA-HQ-ORD-2007-0403

Committee Members:	(See EPA HSRB Members list – Attachment A) 

Dates and Times:  	Tuesday, November 13, 2007, 1:00 PM – 3:00 PM 

(See Federal Register Notice – Attachment B) 

Location: 		via teleconference 

Purpose: 	The EPA HSRB provides advice, information, and recommendations
on issues related to the scientific and ethical aspects of human
subjects research. 

Attendees: 	Chair: 			Celia B. Fisher, Ph.D.

Board Members: 	Alicia Carriquiry, Ph.D.

			Janice Chambers, Ph.D., D.A.B.T.

Richard Fenske, Ph.D., MPH

Suzanne C. Fitzpatrick, Ph.D., D.A.B.T.

Dallas E. Johnson, Ph.D.

Kannan Krishnan, Ph.D.

Michael D. Lebowitz, Ph.D., FCCP

Jerry A. Menikoff, M.D.

Rebecca Parkin, Ph.D., MPH 

Sean Philpott, Ph.D., M.Bioethics

Richard R. Sharp, Ph.D. 

Meeting Summary:	Meeting discussions generally followed the issues and
general timing as presented in the meeting Agenda (Attachment C), unless
noted otherwise in these minutes. 

Introductory Remarks, Meeting Administrative Procedures, and Meeting
Process

Dr. Celia Fisher (HSRB Chair) opened the teleconference meeting with an
introduction and identification of the HSRB members participating in the
call.  Dr. Fisher explained that the purpose of the meeting was to
review and approve the June 27-29, 2007 draft HSRB meeting report
(Attachment D).  

Dr. Paul Lewis (Designated Federal Officer [DFO], HSRB, Office of the
Science Advisor [OSA], EPA) thanked Dr. Fisher and the Board for their
participation in the teleconference and for their review of the draft
June 27-29, 2007 HSRB meeting report.  Dr. Lewis explained that the HSRB
is subject to Federal Advisory Committee Act (FACA) requirements.  As
the DFO, Dr. Lewis serves as liaison between the HSRB and EPA, or the
Agency.  He works with the appropriate officials to ensure compliance
with all appropriate ethics regulations.  Each member of the Board has
filed a standard government financial disclosure form that has been
reviewed by EPA to ensure that all ethics disclosures have been met.

Dr. Lewis stated that the documents discussed by the HSRB, including the
draft June 27-29, 2007 HSRB meeting report, are available at the public
docket; the address for the docket was included in the Federal Register
notice announcing this teleconference meeting.  As per FACA
requirements, the meeting minutes will include descriptions of matters
discussed and the conclusions reached by the Board.  As the DFO,
Dr. Lewis will prepare the minutes and have them certified by the HSRB
Chair within 90 calendar days of the meeting.  In addition, the minutes
will be available at the public docket and posted on the HSRB Web site. 


Public Comments

Dr. Fisher invited oral public comment on the draft June 27-29, 2007
HSRB meeting report.  No oral public comments were presented.  

Board Discussion and Decision on Report

Dr. Fisher introduced the written comments submitted by the EPA Office
of Pesticide Programs (OPP) and stated that the Board discussion during
the teleconference would focus on questions and points of clarification
raised by OPP.  Dr. Fisher suggested that the Board adopt all OPP
recommendations that were factual, grammatical, or editorial
corrections.

The Board’s letter to Dr. George Gray (Science Advisor, EPA)
summarizes the Board consensus and rationale regarding charge questions
raised at the June 27-29, 2007 meeting.  OPP’s comments on the letter
are related to comments made within the body of the draft meeting
report; therefore, Drs. Fisher and Lewis will revise the letter as
needed based on Board discussions during the teleconference.

Proposed Carroll-Loye Picaridin Insect Repellent Efficacy Study LNX-001

Dr. Fisher asked if Board members had any suggested changes to the HSRB
Consensus and Rationale related to scientific considerations (p. 17,
lines 39-43).  No Board members requested changes.

OPP’s written comments suggested that the minimum and maximum numbers
of subjects participating in this study were incorrect within the
meeting report text.  “The number of participants enrolled in this
study thus will total a minimum of 25 volunteers and a maximum of 37
volunteers, a number that appears to be adequately justified (Carroll
2007a; Carroll 2007b)” (p. 19, lines 11-13).  OPP’s written comments
stated that the minimum number of subjects should be 22 and the maximum
should be 54.  Dr. Fisher requested feedback from the Board on whether
to delete the sentence or incorporate OPP’s suggested changes.  Dr.
Sean Philpott disagreed with OPP’s comment because the minimum of 22
participants does not take into account the 3 alternate participants. 
Dr. Philpott indicated that he had discussed the number of study
participants in great detail with Dr. Scott Carroll (Carroll-Loye
Biological Research, Inc.) during preparation of this section of the
draft meeting report and concluded that a maximum of 37 participants
will participate in both field studies.  Dr. Fisher stated that the
sentence in the meeting report concerning minimum and maximum numbers of
participants would not be revised.

Within the ethics discussion for this study (p. 19, lines 23-38),
OPP’s written comments requested clarification on whether the Board
intended to state that the protocol meets the standards of 40 Code of
Federal Regulations (CFR) 26.1125 rather than state that it meets all
requirements of 40 CFR part 26, subparts K and L, being that the
paragraph focused specifically on 40 CFR 26.1125.  Dr. Philpott, who
authored this section of the meeting report, explained that he had
replicated the language used in the charge question, but agreed that the
meeting report could be changed to cite the specific documentation
requirement. 

Dr. Fisher inquired if Board members had changes or comments for the
HSRB Consensus and Rationale related to ethical considerations (p. 21,
lines 4-10).  No changes were suggested.

Proposed ICR Picaridin Insect Repellent Efficacy Study

Dr. Fisher asked if Board members had changes or comments for the HSRB
Consensus and Rationale related to scientific considerations (p. 24,
lines 24-29).  No changes were suggested.

For the Board’s discussion of the background of the picaridin study,
OPP’s written comments suggested several changes to the text in order
to clarify the difference between a confirmed bite (a bite confirmed by
another bite in the same or the next subsequent exposure period) and the
premise in the Insect Control and Research, Inc. (ICR) protocol that ICR
staff will determine whether to count an event as a bite (p. 25, lines
31-37).  Dr. Fisher stated that she planned to incorporate OPP’s
comments.  Dr. Philpott agreed that OPP’s changes were correct and
would more accurately reflect EPA guidelines.  In the following
paragraph, OPP’s written comments clarified that a rate of 1 to 10
landings per minute, not a “minimum” rate of 1 to 10, is necessary
for conducting the field trial (p. 25, line 45).  Dr. Fisher proposed
revising the sentence as follows:  “A minimum rate of 1 and a maximum
rate of 10 landings per minute are necessary for the field trial to be
conducted.”  The Board members agreed with this change.

OPP’s written comments questioned the use of quotation marks around
the phrase “substantially compliant” (p. 26, line 36).  Drs.
Philpott and Fisher agreed to remove the quotation marks, but noted that
the Board had discussed at a previous meeting the meaning of
“substantially compliant” and that the definition remains unclear. 
In the same sentence, OPP’s written comments requested clarification
of the phrase “the regulatory requirements of review and
documentation” (p. 26, line 37).  The Board agreed to revise the
phrase as follows:  “…the regulatory requirements of review and
documentation in 40 CFR 26.1125…”

	On page 27, lines 26-28, OPP’s written comments clarified that EPA
guidelines do not mention landings as an endpoint, although EPA has
accepted studies that use landings as an endpoint.  Dr. Philpott
explained that this passage was intended to reflect ICR’s and
toXcel’s justification for use of time to first confirmed bite (FCB)
by referring to EPA guidelines in their written response to OPP.  Dr.
Fisher noted that OPP may be concerned that this statement suggests that
EPA guidelines do call for landings with intent to bite.  She proposed
adding a sentence to this passage to clarify that use of landings with
intent to bite as an endpoint is not part of EPA’s guidelines.  Dr.
Philpott agreed with this proposed revision.

Dr. Fisher asked if Board members had changes or comments for the HSRB
Consensus and Rationale related to ethical considerations (p. 29, lines
37-41).  No changes were suggested.

Completed Inhalation Study with Acrolein

OPP’s written comments requested clarification of the Board’s
consensus that “…the study was sufficiently sound, from a scientific
perspective, to be used to estimate a safe level of acute inhalation
exposure to acrolein for the population tested” (p. 33, lines 44-45). 
OPP inquired as to whether the Board meant that the results cannot be
generalized beyond the population tested.  Dr. Fisher suggested revising
the sentence to reflect that the Board did not believe the results could
be generalized to younger or older population groups than those used in
the study.  Board members agreed with this revision. 

Regarding the Weber-Tschopp et al. study, the Board states that
“…post hoc benefit is not relevant…” (p. 37, line 2) and OPP’s
written comments requested clarification.  The Board discussed that at
least one Board member found the risk-to-benefit balance to be
inappropriate.  Dr. Fisher proposed revising the text as follows to
clarify the Board’s position:  “…post hoc benefit is not relevant
to the prospective risk-benefit balance…”  Dr. Jerry Menikoff agreed
with the suggested change.

Dr. Fisher asked if Board members had changes or comments for the HSRB
Consensus and Rationale related to ethical considerations (p. 37, lines
7-13).  No changes were suggested.

Completed Studies on the Therapeutic and non-Therapeutic Effects of
Administration of 4-aminopyridine

Dr. Fisher inquired if Board members had changes or comments for the
HSRB Consensus and Rationale related to scientific (p. 40, lines 10-20)
and ethical considerations (p. 42, lines 22-28).  No changes were
suggested.

Design of Research on the Levels of Exposure Received by Pesticide
Handlers

Risks and Benefits of Handler Research

OPP’s written comments expressed a general concern that the draft
meeting report focused on the Agricultural Handlers Exposure Task Force
(AHETF) to the exclusion of the Antimicrobial Exposure Assessment Task
Force (AEATF).  Based on OPP’s comments, Dr. Richard Fenske, who
authored this section of the meeting report, made revisions throughout
this section and submitted his revisions to Dr. Fisher prior to the
teleconference.  On page 43, lines 20-24, Dr. Fenske suggested revising
the text to include risks relevant to the AEATF protocols, as described
in the June 2007 HSRB meeting minutes.  Dr. Fisher inquired about the
Board’s critique (p. 43, lines 30-31) and how discussion of AEATF
should be incorporated.  Dr. Fenske suggested the addition of a
sentence noting that most of the Board’s comments are applicable to
the AEATF document in addition to AHETF document.  Reference to “the
document” should be changed to plural (“the documents”).

On page 44, lines 6-7, Dr. Fenske proposed adding a sentence to indicate
that participants would receive the benefits of use of test substances
at no cost; however, Mr. John Carley (OPP, EPA) clarified that the
benefit of free product would not apply to AEATF protocols because most
of these protocols would be performed in leased vacant buildings. 
Participants recruited from janitorial service companies would apply the
products.  Dr. Fenske agreed to modify the text to reflect this.

	Dr. Fenske explained that the subsequent paragraph (p. 44, lines
15-26), concerning use of farm equipment, is applicable only to the
AHETF and not the AEATF.  On page 44, lines 28-37, Dr. Fenske suggested
the addition of text at the end of the paragraph to indicate that the
same recommendations could be applied to the AEATF, but risks for AEATF
protocols would be lower. 

Dr. Fisher requested comments on the HSRB Consensus and Rationale (p.
45, line 24 through p. 46, line 2).  Dr. Fenske suggested the addition
of AEATF to the first line of the consensus statement, indicating that
both groups have provided the HSRB with appropriate and useful governing
documents.  Dr. Fenske also proposed the addition of AEATF to the final
sentence of the paragraph, concerning the ability of data collected by
both task forces to improve the quality of risk assessments and provide
valuable societal benefits.  Dr. Fenske agreed to incorporate the
discussed revisions into this section of the report and to submit the
revised text to Drs. Fisher and Lewis after conclusion of the
teleconference.

Addressing Potential Sources of Underestimation Bias

OPP’s written comments stated that although face/neck wipe sampling is
not mentioned in the draft Agency 875 guidelines, EPA would not reject
studies including face/neck wipes (p. 46, lines 44-46).  Dr. Michael
Lebowitz suggested adding a statement clarifying that wipe sampling is
not included in EPA guidelines, but EPA will accept such information. 
Dr. Fisher clarified that the sentence will be changed as follows: 
“This method was not among those recommended by the Agency in its 1987
Subdivision U Agency guidelines for pesticide handler exposure studies,
but this does not mean that EPA would not accept its use.”  Dr. Fenske
agreed with this revision.  

OPP’s written comments also questioned the following statement: 
“Nor was wipe sampling included as an appropriate method in the 1997
guidance document produced by the Organization for Economic Cooperation
and Development (OECD 1997)” (p. 47, lines 1-3).  OPP commented that
page 29 of the OECD document states:  “Exposure to the head, neck and
face should be determined by measuring deposition on a cotton hat or
cap, on a hood as part of the whole body dosimeter, or on a head patch
as for the patch method.  Exposure to the face and neck could also be
determined through the use of wipe samples.”  Dr. Fenske stated that
he agreed with OPP’s comment and suggested deleting the entire
sentence.

On page 48, lines 1-2, OPP’s written comments requested clarification
of the sentence describing potential underestimation of exposure using
removal techniques that remove only chemicals that have not been
adsorbed onto or absorbed into the skin.  OPP’s comments explained
that hand rinse and face wipe methods are designed to remove adsorbed
materials. Dr. Fenske suggested revising this sentence as follows: 
“Removal techniques typically underestimate exposure, since they can
only remove chemicals that have not been adsorbed irreversibly onto or
absorbed into the skin.”  The Board agreed with this revision.

OPP’s written comments suggested deleting the paragraph on page 48,
lines 28-34.  Dr. Fenske agreed to delete the first two sentences from
this paragraph. He believed it would be appropriate to retain the
remainder of the paragraph, and to add a sentence indicating Board
support of Agency plans to evaluate the relative importance of hand,
neck and face exposure from each study as planned by the task forces. 
He recommended adding language contained in OPP’s comment regarding
evaluation of data from each study, and recommended spelling out “Task
Forces” and “whole body dosimetry,” rather than using acronyms. 
Dr. Fenske will incorporate the revisions discussed during the
teleconference into this section and will submit the revised text to
Drs. Fisher and Lewis.

Dr. Fenske also suggested modifying the sentence “In both cases, a
validation study for recovery efficiency of wash or wipe samples can be
tested in vitro…” (p. 49, lines 21-22) to “…could be tested in
vitro…”

OPP’s written comments pointed out that the HSRB Consensus and
Rationale (p. 49, line 27) was not included in the draft meeting
report; therefore, Dr. Fisher developed a draft of the conclusions for
Board approval.  Dr. Fisher read her draft text and Dr. Fenske reviewed
the draft Consensus and Rationale and agreed to incorporate revisions
discussed during the teleconference and to submit the revised text to
Drs. Fisher and Lewis. 

Dr. Fisher requested comments on the HSRB Consensus and Rationale
regarding the appropriateness of not including concurrent biomonitoring
in the protocols (p. 50, lines 26-30).  No changes were suggested.

QA and QC Controls

OPP’s written comments noted that the HSRB Consensus and Rationale
related to quality assurance (QA) and quality control (QC) controls (p.
51, line 21) was not included in the draft meeting report; therefore,
Dr. Fisher developed a draft of the conclusions for Board approval. 
“Overall, the SOPs [Standard Operating Procedures] outlining the
overall administration, report generation and quality assurance (QA)
oversight seems reasonably complete.  The HSRB reviewers noted two major
areas that should be expanded and/or revised for additional clarity,
namely the SOPs that focused on data quality and sample integrity and
compliance.”  Dr. Lewis requested that “The HSRB reviewers…” be
changed to “The Board…”  No other changes were suggested.

Design of Scenario-Level Sampling Strategies

OPP’s written comments requested clarification on whether the
Board’s description of the number of handler-days included both the
AHETF and AEATF programs (p. 51, lines 39-40).  “It was estimated that
this would include approximately 1.1 million handlers and approximately
2 million handler-days.”  Dr. Fenske suggested revising the text to
“It was estimated by the AHETF that this would include…”

OPP’s written comments also questioned the Board’s statement that
“…complex probability sampling is more typical for these types of
projects” (p. 51, lines 42-43) and requested more specificity in
regard to the types of projects the Board was referring.  Dr. Fenske
agreed that this sentence is confusing and suggested that the sentence
be deleted.  Dr. Fisher asked Mr. Carley if he found this revision to be
acceptable and he indicated agreement with the change.  On page 51, line
45, the Board decided to revise “Complications associated with complex
probability sampling…” to “Considerations associated with
sampling…”

Dr. Alicia Carriquiry questioned the sentence referring to selection
bias as a particular issue for protocols that will only use volunteers
(p. 52, lines 1-2); she asked Mr. Carley to provide an example of a
study that does not use volunteers.  Mr. Carley suggested that studies
based on Census data do not use volunteers and clarified that EPA had
not asked for revision or clarification of this particular sentence. 
Dr. Carriquiry noted that selection bias is an issue for all protocols,
not “a particular issue for these protocols…” Dr. Lebowitz stated
that the use of the term “volunteers” may be problematic because
there is concern about inappropriate pressure to participate placed on
potential participants since they are workers; he felt that selection
bias is an issue and that the sentence is accurate.  For the AHETF,
participants represent a convenient sample, not a randomly selected
sample.  Dr. Carriquiry remarked that she believed the purpose of this
sentence was for EPA to justify use of purposive diversity sampling
(PDS) by stating that if random sampling is used, people can refuse to
participate.  The Board agreed to delete this sentence.

OPP’s written comments stated:  “The primary purpose of the Task
Forces’ proposed research is collection of improved measurements of
the range of individual handler exposure-days for the various scenarios.
 Generation of data to assess the relationship of the active ingredient
to exposure is a secondary goal.”  The Board agreed with OPP’s
comment and agreed to change the phrase “the primary driver of the
study design” (p. 53, line 16) to “an important driver of the study
design.”

	OPP’s written comments indicated that the discussion regarding study
factors and variables (p. 53, lines 17-29) is specific to the AHETF
program and that it would be helpful for the Board to include comments
concerning the AEATF program.  Dr. Lebowitz clarified that the entire
paragraph refers to the AHETF program and that the AEATF was not
discussed in this regard during the June 2007 HSRB meeting.  Dr. Fenske
suggested adding, “For example, in the AHETF study…” The Board
agreed to this revision.

On page 53, lines 27-29, “The Board concluded that any attempt at
diversity sampling should include an appropriate number of non-certified
applicators.” OPP’s written comments indicated that this
recommendation seemed to reflect an incomplete understanding of the
regulatory requirements regarding applicator certification.  Many
applicators who apply restricted use pesticides are not themselves
certified, but make applications under the supervision of a certified
applicator.  Dr. Fenske referred to Board discussion during the June
2007 HSRB meeting concerning the wide variety of qualifications of
certified applicators and variations in the quality of supervision of
those working with them.  This prompted the Board to include a statement
within the draft meeting report concerning inclusion of an appropriate
number of non-certified handlers because these workers are likely to
have the highest exposure levels.  Mr. Carley agreed that Dr.
Fenske’s response clarified the Board’s intent but noted that most
handlers participating in the AHETF protocols will be non-certified.  He
agreed that the Board’s statement concerning inclusion of
non-certified handlers could remain, but that it should be clarified
that this recommendation refers to AHETF protocols.  Dr. Fenske
suggested that for the HSRB Consensus and Rationale (p. 53, lines
35-44), a sentence could be added indicating that Board discussions at
the June 2007 meeting focused on AHETF and that not all recommendations
would apply to the AEATF.

On page 53, lines 31-33, “The Board recommended that the Agency
develop a process whereby the critical variables associated with
exposure are ranked, accompanied by an appropriate rationale and
justification for the ranking.”  OPP’s written comments requested
clarification on whether the HSRB was suggesting that EPA define the
process by which the task forces should identify and rank all critical
variables and fully document their rationale and justification for the
ranking.  Dr. Fisher clarified that the Board believed a process would
be needed, but did not want to define a specific process. Dr. Lebowitz
added that if EPA wishes to use the data in the most optimal fashion,
EPA should develop a process for identification, ranking, documentation,
and justification of critical variables and should provide the Board
with the rationale and documentation.  This should be done before the
exposure experiments are conducted. Dr. Fenske recommended that OPP be
allowed some degree of flexibility in defining these activities. Mr.
Carley commented that EPA believes strongly that the task forces should
rationalize and document all critical factors included in designing
sampling strategies.  EPA plans to require this information in order for
the data to be usable, but EPA is not interested in defining the actual
process.  Dr. Fisher suggested that the word “process” could be
removed. Mr. Carley suggested recommending that EPA ensures that the
critical variables associated with exposure are ranked and that
justification for the ranking is described.  Dr. Fisher agreed and added
that this should occur prior to data collection and these activities
should be performed by both task forces.  The Board agreed to revise the
sentence as follows:  “For both AHETF and AEATF, the Board recommended
that prior to data collection the Agency ensure critical variables
associated with exposure are ranked…”  Mr. Carley noted that the
same sentence appears within the HSRB Consensus and Rationale (p. 53,
lines 42-44).  There were no further comments for the HSRB Consensus and
Rationale (p. 53, line 35-44) other than revising the last sentence.

OPP’s written comments pointed out that the HSRB Consensus and
Rationale (p. 55, line 6) for the charge question regarding the need
for scenario-specific information, the availability of data to identify
significant variables potentially influencing exposure, and the
feasibility of developing a sampling strategy to address the variables
quantitatively was not included in the draft meeting report.  Dr. Fisher
prepared a draft of this text and distributed it to the Board for
review:  “The Board recommended that the following information was
necessary for it to provide its scientific advice:

Scenario-specific information detailing variables that might influence
exposure and its effect;

A feasible sampling strategy including specifics of population to be
tested (including its size), a list of relevant variables and how they
would be collected and analyzed;

Information on relationships between scenario-specific exposure
assessment and the representative exposure in such scenarios in the
target population;

Essential environmental variables including site description,
temperature, humidity, and wind levels as well as subjects’ external
clothing, work history and type of pesticide application;

Relevant data on inter-subject variability; and

A data analysis plan.”

	Dr. Fisher asked the Board members for comments on the proposed
conclusion.  No changes were suggested.

On page 56, lines 6-7, the meeting report states, “The sample size
that we are concerned with in these studies is 25 and not 5 as is argued
in the Governing Documents.”  OPP, in its written comments states,
“OPP thinks the effective sample size of a 5 X 5 sampling design would
be somewhere between 5 and 25.  As described in Snijders and Bosker (p.
23), based on an ICC [intraclass correlation coefficient] of 0.3 (for
sampling locations) the effective sample size is approximately 11 for
this design.”  Dr. Carriquiry noted that the effective sample size of
11 appears to be correct; however, she felt OPP’s written comment
concerning the usefulness of random sampling for such a small sample
size was incorrect.  She believes random sampling is preferable to PDS
for small samples.  Dr. Carriquiry agreed to re-phrase this paragraph to
address issues regarding the appropriateness of random sampling and to
confirm that the sample size and 5 X 5 sampling design was appropriate. 
Dr. Carriquiry will submit the revised text to Drs. Fisher and Lewis.

 

OPP’s written comments requested clarification of the phrase
“conceptually large” (p. 56, lines 17-18).  Dr. Carriquiry explained
that “conceptually large” usually refers to infinity, which is
described as 30 by statisticians; this refers to the number of purposive
samplers, not the sample itself.  She explained that the point of
referring to a “conceptually large” number of purposive samplers was
to imply that purposive sampling can be unbiased; this is true only if
there are many purposive samplers and the data are averaged over their
sample.  Dr. Fisher agreed to clarify this sentence to read that “This
is true if we have a large number of purposive samplers and average over
them (central limits theorem).” 

OPP’s written comments requested clarification of the Board’s
conclusion that EPA’s arguments regarding the cost of random sampling
were not convincing and that use of random sampling would cost more than
PDS.  Dr. Carriquiry explained that, relative to the cost of collecting
and analyzing the data, the difference in costs between using PDS versus
random sampling was not large.  PDS is less costly, but the difference
is not large relative to the cost of the entire study.  Dr. Lewis agreed
to add a line to this paragraph clarifying the Board’s position on
cost.  Dr. Carriquiry noted that the Board was speculating about costs
in the absence of relevant information and suggested that the task
forces present cost estimates for both sampling strategies relative to
other costs.  Dr. Fisher interjected that she was unsure whether such a
discussion would fall under the purview of the Board, but perhaps such
issues could be discussed during the Board work group meeting at which
sampling issues for the task forces will be discussed.

OPP’s written comments questioned whether the Board’s suggestions
regarding random sampling (p. 56, lines 40-41) also applied to AEATF
research.  Dr. Carriquiry stated that the recommendations would be
slightly different and offered to re-write recommendations for the
AEATF.  Dr. Lewis cautioned that it could be problematic to add new
recommendations to the meeting report without Board discussion and
approval.  Dr. Carriquiry clarified that the recommendations would not
be new, but would merely be re-phrased to apply to the AEATF
(i.e., removing references to farming equipment).  Dr. Fisher noted
that purposive selection of locations (p. 56, line 42) would apply to
AEATF, although counties or groups of counties would refer only to
AHETF.  She proposed deletion of “(e.g., counties or group of
counties)” from the first bullet.  The suggestion regarding farming
operations (p. 56, lines 43-44) would apply only to AHETF.  Board
suggestions regarding stratification of producers by crop and size (p.
56, line 45), and random selection of producers (p. 57, lines 1-2) could
be re-worked to apply to AEATF by changing “producers” to
“operations” and by describing appropriate AEATF variables for
stratification and selection.  The Board agreed to change the fourth
bullet as follows:  “Randomly select operations and within operations,
randomly select operators.”  Mr. Carley suggested use of the term
“handler” rather than “operator.”  The Board agreed to this
revision.  In response to OPP’s comment, the Board agreed to remove
the last suggestion concerning focusing on fewer scenarios (p. 57, lines
3-4).

Regarding the Board’s suggestion to randomly select producers within
sub-stratum and randomly select handlers within producers, OPP’s
comments inquired how to cope with a low rate of response and limited
pool of applicants.  Dr. Carriquiry explained that the main sampling
unit is the operation and that, within the operation, there may be one
or two handlers; the main concern is whether the operation agrees to
participate.  Mr. Carley stated that previous task force experience
suggests that random selection of operations will yield a response rate
significantly lower than 10 percent.  He asked the Board for guidance
for coping with this expected low response rate.  Dr. Carriquiry noted
that the low response rate would affect both PDS and random sampling
strategies; however, if PDS is used, operators known to be willing to
participate will be chosen which raises significant selection bias
issues.  She added that a 10-percent response rate seems unusually low. 
Dr. Fisher clarified that both PDS and random sampling designs do not
solve the issue of the low response rate, but random sampling may be
able to provide a degree of variability that PDS cannot.  Dr. Carriquiry
explained that choosing operations using PDS may result in selection of
sites that have characteristics different than other sites that may have
been chosen using a random sampling design; this would decrease the
representativeness of the results.

Mr. Carley recommended that the text within the meeting report stating
that random sampling is no more costly than PDS (p. 56, lines 29-40)
should be revised, in light of the Board’s discussion during the
teleconference concerning lack of information on costs; the sentence
could be changed to indicate that random sampling may be no more costly
than PDS.  He re-iterated that EPA needs advice from the Board for
coping with the expected low response rate.  Dr. Lebowitz explained that
random sampling avoids biases and assumptions and allows the data to be
used more effectively for risk assessment activities.  Dr. Fisher
suggested that the report state that “random sampling is no more
impractical and may be no more costly within the context of the costs of
the whole study than PDS.  Irrespective of response rate, random
sampling provides more information regarding the representativeness of
participating sites or operations.”  Dr. Carriquiry offered to add a
sentence indicating that the Board wishes to consult with experts who
have experience with low response rates.  Dr. Fisher remarked that this
subject should be addressed during the Board’s work group discussions.

For the HSRB Consensus and Rationale (p. 57, lines 8-18), OPP’s
written comments inquired as to why exposure experiments for regulatory
purposes should be based on random sampling.  Dr. Lebowitz explained
that risk assessments based on biased samples have been shown to be
inaccurate and also have raised legal issues; EPA has been sued because
of risk assessments derived from biased samples.  The more
representative the population from which risk assessment decisions are
made, the more likely the risk assessment will be legally acceptable. 
Dr. Fisher agreed to add a statement indicating that risk assessments
based on random samples tend to have less bias, are more informative,
and defensible for regulatory purposes.  Mr. Carley stated that although
he understood this conclusion, the report does not indicate that the
Board deliberated on this matter during the June 2007 HSRB meeting; he
suggested adding information concerning this conclusion to the report. 
Dr. Lebowitz suggested adding a reference to a National Academy of
Sciences report that described this issue.  He agreed to send the
reference to Dr. Lewis, who offered to place the reference in the
meeting report.  In addition, the Board agreed to change “will be used
for regulatory purposes” to “will be used by EPA” and agreed to
remove the word “particularly” from the sentence (p. 57, line 14).

Statistical Justification for Number of Clusters and Monitoring Units

On page 57, lines 39-40, the meeting report states:  “In both
programs, the purposive sampling is used to select clusters and MUs
[monitoring units] within clusters, and as such the sampling of the
clusters and the MUs within clusters is not random.” In its written
comments, OPP stated that the task forces propose purposive selection of
the sites, but once a location is selected, the task forces will
randomly draw subject from among the workers who volunteer; therefore,
selection of MUs within a cluster is proposed to be random.  Dr.
Carriquiry explained that random selection of sites is important and
subsequent selections are less important.  For example, a state could be
purposively selected, then operations randomly selected within the
strata.  Selection of monitoring units within a cluster also should be
random.  The Board agreed to revise the sentence as follows:  “In both
programs, the purposive sampling is used to select clusters; however,
the sampling of MUs within clusters will be random.” The Board
determined that the remainder of the paragraph was correct.

On page 58, lines 26-28, the meeting report states:  “As long as a
cluster size of 5 is not exceeded, the same total number of MUs (N=25)
will also achieve this same level of relative accuracy even if the
number of MUs per cluster varies.”  OPP’s written comments indicated
that this statement did not appear to agree with the results of the task
force simulations regarding variation in cluster sizes.  Dr. Carriquiry
explained that the number of MUs per cluster should be approximately
equal, and suggested adding “slightly” to the end of the sentence. 
The Board agreed with this revision.

On page 59, lines 16-17, the draft meeting report states:  “…the
choice of only three clusters by the AEATF seems risky and it should be
increased if at all possible.”  In its written comments, OPP indicated
that the Board’s conclusion in the draft report seems inconsistent
with the Board’s recommendations made during the June 2007 meeting. 
Dr. Carriquiry explained that the Board agrees that increasing the
number of clusters is costly; however, if the task forces can afford it,
increasing the number of clusters would be an effective way to increase
sampling. She suggested removing the word “strong” from line 22 to
emphasize that from an analysis point of view, increasing the number of
clusters is desirable, but the Board is aware of cost limitations.  She
also suggested including OPP’s comment regarding increased costs when
adding more clusters.  The following sentence will be added to the end
of the paragraph (p. 59, line 24):  “Costs increase if you have to
rent more buildings instead of studying more subjects per building.”

Regarding the HSRB Consensus and Rationale (p. 59, line 32-34), OPP’s
written comments stated that the Agency believes that the potential
sampling bias is unknown and not measurable.  The Board agreed with
OPP’s comment concerning the inability to measure bias and agreed to
delete the following sentence from the meeting report:  “Unless the
surrogate sampling method of purposive sampling is changed to the more
statistically appropriate clustered random sampling, the sponsors should
consider monitoring the potential bias resulting from such surrogate
sampling.”

Within-Worker Variability

OPP’s written comments stated that the Agency believes the “impact
of ignoring the within-person variance” (p. 60, line 10) is modest and
acceptable since the Agency is interested in the distribution of
single-day exposures, not the distribution of usual exposures. 

Dr. Carriquiry stated that if OPP is interested in only single-day
exposure, a large number of workers would need to be monitored instead
of repeated measurements of the same worker.  She questioned OPP’s
need for single-day measurements rather than collecting data over many
days to determine usual exposure.  Dr. Janice Chambers questioned the
ability to obtain repeated measurements of a worker if the exposure
scenario would not be repeated, as may occur in some agricultural
settings.  Dr. Carriquiry stated that it would be desirable to average
exposure over conditions (wind, temperature, etc.) because the exposure
will change.  Measuring exposure only on a single day determines
exposure only for that set of conditions and is irrelevant from a policy
point of view.  Dr. Chambers noted that such repeat measurements require
including similar scenarios, but random sampling will eliminate some of
these scenarios.  Dr. Fisher suggested recommending that repeat measures
be collected for some workers to determine within-worker variability for
a subset of the handlers.  If it is not possible to collect repeated
measurements on the same person under the same conditions, time could be
used as a repeated variable to determine if exposure remains consistent.
 Dr. Carriquiry argued for changing the sampling design rather than
collecting information from the same conditions for different handlers. 
The variance of distribution will be higher than what it should be.  She
added that it is easier to increase the sample size than to increase the
number of observations per worker.  She recommended deleting lines 19-21
and 23-24 on page 60 of the draft meeting report.  Dr. Fisher suggested
adding to the sentence beginning on line 14, “If the objective of the
study is to obtain an estimate of the mean exposure of workers in a
given scenario or to obtain an estimate of the one-day distribution of
exposure…”  In line 36, the word “however” will be removed.

Based on OPP’s comments, the Board agreed to delete the following
sentence (p. 61, line 14):  “The gain in information is likely to
more than compensate for the increased cost.”  The Board also agreed
to replace the word “replicate” (p. 61, lines 4 and 6) with
“within-person repeated observations.” 

OPP’s written comments pointed out that the HSRB Consensus and
Rationale (p. 61, line 40) was not included in the draft meeting
report.  Dr. Fisher asked the Board members for suggestions on the
conclusion for this issue.  Dr. Carriquiry suggested that the Board
recommend that the task forces collect data for as many handlers as cost
will allow.  Dr. Fisher suggested adding a statement indicating that the
lack of choosing a within-person design is limiting if EPA wishes to
obtain data on usual exposure; however, if EPA wishes to collect data on
one-day exposure, their approach is not limiting, but the Board
recommends that as many handlers as possible are observed.

Subject Recruitment and Enrollment Issues

OPP’s written comments requested explanation of the basis for assuming
vulnerability of many of the prospective subjects (p. 62, line 35).  Dr.
Menikoff clarified that, in this case, vulnerability referred to
economic (i.e., working for an employer who wishes to participate in the
study), educational, and language issues.  Dr. Fisher proposed revising
the beginning of the sentence as follows:  “Give the language,
economic and educational characteristics of the prospective
subjects…”  OPP’s written comments also explained that many
employers, such as farmers or an aerial application service, do not have
as many as 50 employees who could participate in the study (p. 62, line
38).  The Board agreed to lower the example of “25 out of 50” to
“5 out of 10.”

Dr. Fisher asked the Board members for comments on the HSRB Consensus
and Rationale for this section (p. 62, lines 43-46).  No changes to the
text were suggested.

Summary and Next Steps

Dr. Fisher asked each Board member for their approval of the revised
June 27-29, 2007 draft meeting report, including acceptance of the
points of factual clarification and grammatical changes raised by OPP
which were not discussed during the teleconference.  All Board members
in attendance at the teleconference meeting approved the report.  

Dr. Lewis thanked Board members for their preparation for and
participation in the conference call and for their work on the report. 
Dr. Lewis stated that he and Dr. Fisher will revise the report based on
comments made during the teleconference.  The revised report will be
released at regulations.gov and posted on the HSRB Web site.  The next
face-to-face HSRB meeting is scheduled for January 15-18, 2008.  

The meeting was adjourned by the Chair.

Respectfully submitted:

Paul I. Lewis, Ph.D.

Designated Federal Officer

Human Studies Review Board

United States Environmental Protection Agency

Certified to be true by:

Celia B. Fisher, Ph.D.

Chair

Human Studies Review Board

United States Environmental Protection Agency

NOTE AND DISCLAIMER:  The minutes of this public meeting reflect diverse
ideas and suggestions offered by Board members during the course of
deliberations within the meeting.  Such ideas, suggestions, and
deliberations do not necessarily reflect definitive consensus advice
from the Board members.  The reader is cautioned to not rely on the
minutes to represent final, approved, consensus advice and
recommendations offered to the Agency.  Such advice and recommendations
may be found in the final report prepared and transmitted to the EPA
Science Advisor following the public meeting.

Attachments 

Attachment A 		HSRB Members 

Attachment B 		Federal Register Notice Announcing Meeting 

Attachment C 		Meeting Agenda 

Attachment D 		June 27-29, 2007 EPA Human Studies Review Board Meeting 

Proposed Final Draft Report 

Attachment A

EPA HUMAN STUDIES REVIEW BOARD MEMBERS 

Chair

Celia B. Fisher, Ph.D.

Marie Ward Doty Professor of Psychology

Director, Center for Ethics Education

Fordham University

Bronx, NY 

Vice Chair

William S. Brimijoin, Ph.D.*

Chair and Professor 

Molecular Pharmacology and Experimental Therapeutics

Mayo Foundation

Rochester, MN 

Members

Alicia Carriquiry, Ph.D.

Professor 

Department of Statistics

Iowa State University

Ames, IA 

Gary L. Chadwick, PharmD, MPH, CIP*

Associate Provost

Director, Office for Human Subjects Protection

University of Rochester

Rochester, NY 

Janice Chambers, Ph.D., D.A.B.T.

William L. Giles Distinguished Professor

Director, Center for Environmental Health Sciences

College of Veterinary Medicine

Mississippi State University

Mississippi State, MS 

Richard Fenske, Ph.D., MPH 

Professor

Department of Environmental and Occupational Health Sciences

University of Washington

Seattle, WA 

Susan S. Fish, PharmD, MPH*

Professor, Biostatistics & Epidemiology

Boston University School of Public Health

Co-Director, MA in Clinical Investigation

Boston University School of Medicine

Boston, MA 

Suzanne C. Fitzpatrick, Ph.D., DABT

Senior Science Policy Analyst

Office of the Commissioner

Office of Science and Health Coordination

U.S. Food and Drug Administration

Rockville, MD 

Dallas E. Johnson, Ph.D.

Professor Emeritus

Department of Statistics

Kansas State University

Manhattan, KS

KyungMann Kim, Ph.D., CCRP*

Professor and Associate Chair

Department of Biostatistics & Medical Informatics

School of Medicine and Public Health

University of Wisconsin-Madison

Madison, WI 

Kannan Krishnan, Ph.D.

Professor

Département de santé environnementale et santé au travail

Faculté de médicine 

Université de Montréal

Montréal, QC  Canada

Michael D. Lebowitz, Ph.D.

Professor Emeritus of Medicine

University of Arizona

Tucson, AZ 

Lois D. Lehman-Mckeeman, Ph.D.*

Distinguished Research Fellow, Discovery Toxicology

Bristol-Myers Squibb Company

Princeton, NJ 

Jerry A. Menikoff, M.D.  

National Institute of Health

Office of Human Subjects Research

Bethesda, MD 

Rebecca Parkin, Ph.D., MPH

Associate Dean for Research and Public Health Practice

School of Public Health and Health Services

The George Washington University

Washington, DC

Sean Philpott, Ph.D., M.Bioethics

Policy and Ethics Director

Global Campaign for Microbicides

Program for Appropriate Technology in Health

Washington, DC  

Ernest D. Prentice, Ph.D.*

Associate Vice Chancellor for Academic Affairs

Professor of Genetics, Cell Biology and Anatomy

Professor of Preventive and Societal Medicine

Omaha, NE 

Richard R. Sharp, Ph.D. 

Director of Bioethics Research

Department of Bioethics

Cleveland Clinic

Cleveland, OH 

* Not in attendance at teleconference

Attachment B

Federal Register Notice Announcing Meeting

Human Studies Review Board (HSRB); Notification of Public Teleconference
  

[Federal Register: October 24, 2007 (Volume 72, Number 205)]

[Notices]

[Page 60361-60362]

From the Federal Register Online via GPO Access [wais.access.gpo.gov]

------------------------------------------------------------------------
-------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-ORD-2007-0403; FRL-8486-1]

Human Studies Review Board (HSRB); Notification of a Public
Teleconference To Review Its Draft Report From the June 27-29, 2007 HSRB
Meeting

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

------------------------------------------------------------------------
-------------------------------------------------------

SUMMARY: The EPA Human Studies Review Board (HSRB) announces a public
teleconference meeting to discuss its draft report from the June 27-29,
2007 HSRB meeting.

DATES: The teleconference will be held on November 13, 2007 from 1 to
approximately 3 p.m. Eastern Time.

Location: The meeting will take place via telephone only.

Meeting Access: For information on access or services for individuals
with disabilities, please contact the Designated Federal Officer (DFO)
at least 10 business days prior to the meeting using the information
under FOR FURTHER INFORMATION CONTACT, so that appropriate arrangements
can be made.

Procedures for Providing Public Input: Interested members of the public
may submit relevant written or oral comments for the HSRB to consider
during the advisory process. Additional information concerning
submission of relevant written or oral comments is provided in Unit I.D.
of this notice.

FOR FURTHER INFORMATION CONTACT: Members of the public who wish to
obtain the call-in number and access code to participate in the
telephone conference, request a current draft copy of the Board’s
report or who wish further information may contact Crystal
Rodgers-Jenkins, EPA, Office of the Science Advisor, (8105),
Environmental Protection Agency, 1200 Pennsylvania Avenue, NW.,
Washington, DC 20460; or via telephone/voice mail at (202) 564-5275.
General information concerning the HSRB can be found on the EPA HSRB Web
site at   HYPERLINK
"http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html
&log=linklog&to=http://www.epa.gov/osa/hsrb/" 
http://www.epa.gov/osa/hsrb/ .

ADDRESSES: Submit your written comments, identified by Docket ID No.
EPA-HQ-ORD-2007-0403, by one of the following methods:

	Internet: http://www.regulations.gov: Follow the on-line instructions
for submitting comments.

	E-mail:   HYPERLINK "mailto:ord.docket@epa.gov"  ord.docket@epa.gov .

	Mail: Environmental Protection Agency, EPA Docket Center (EPA/DC), ORD
Docket, Environmental Protection Agency, Mailcode: 28221T, 1200
Pennsylvania Ave., NW, Washington, DC 20460.

	Hand Delivery: The EPA/DC Public Reading Room is located in the EPA
Headquarters Library, Room Number 3334 in the EPA West Building, located
at 1301 Constitution Avenue, NW., Washington, DC. The hours of operation
are 8:30 a.m. to 4:30 p.m. Eastern Time, Monday through Friday,
excluding Federal holidays. Special arrangements should be made for
deliveries of boxed information. Please contact (202) 566-1744 or e-mail
the ORD Docket at   HYPERLINK "mailto:ord.docket@epa.gov" 
ord.docket@epa.gov  for special instructions.

	Instructions: Direct your comments to Docket ID No.
EPA-HQ-ORD-2007-0403. EPA's policy is that all comments received will be
included in the public docket without change and may be made available
online at   HYPERLINK
"http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html
&log=linklog&to=http://www.regulations.gov"  http://www.regulations.gov
, including any personal information provided, unless the comment
includes information claimed to be Confidential Business Information
(CBI) or other information whose disclosure is restricted by statute. Do
not submit information that you consider to be CBI or otherwise
protected through   HYPERLINK
"http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html
&log=linklog&to=http://www.regulations.gov"  http://www.regulations.gov 
or e-mail. The   HYPERLINK "http://www.regulations.gov" 
http://www.regulations.gov  Web site is an “anonymous access”
system, which means EPA will not know your identity or contact
information unless you provide it in the body of your comment. If you
send an e-mail comment directly to EPA, without going through  
HYPERLINK
"http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html
&log=linklog&to=http://www.regulations.gov"  http://www.regulations.gov
, your e-mail address will be automatically captured and included as
part of the comment that is placed in the public docket and made
available on the Internet. If you submit an electronic comment, EPA
recommends that you include your name and other contact information in
the body of your comment and with any disk or CD-ROM you submit. If EPA
cannot read your comment due to technical difficulties and cannot
contact you for clarification, EPA may not be able to consider your
comment. Electronic files should avoid the use of special characters,
any form of encryption, and be free of any defects or viruses.

	

I. Public Meeting

A. Does This Action Apply to Me?

	This action is directed to the public in general. This action may,
however, be of interest to persons who conduct or assess human studies,
especially studies on substances regulated by EPA, or to persons who are
or may be required to conduct testing of chemical substances under the
Federal Food, Drug, and Cosmetic Act (FFDCA) or the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA). Since other entities may also be
interested, the Agency has not attempted to describe all the specific
entities that may be affected by this action. If you have any questions
regarding the applicability of this action to a particular entity,
consult the person listed under FOR FURTHER INFORMATION CONTACT.

B. How Can I Access Electronic Copies of This Document and Other Related
Information?

	In addition to using regulations.gov, you may access this Federal
Register document electronically through the EPA Internet under the
Federal Register listings at   HYPERLINK
"http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html
&log=linklog&to=http://www.epa.gov/fedrgstr/" 
http://www.epa.gov/fedrgstr/ .

	Docket: All documents in the docket are listed in the   HYPERLINK
"http://www.regulations.gov"  http://www.regulations.gov  index.
Although listed in the index, some information is not publicly
available, e.g., CBI or other information whose disclosure is restricted
by statute. Certain other material, such as copyrighted material, will
be publicly available only in hard copy. Publicly available docket
materials are available either electronically in   HYPERLINK
"http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html
&log=linklog&to=http://www.regulations.gov"  http://www.regulations.gov 
or in hard copy at the ORD Docket, EPA/DC, Public Reading Room. The
EPA/DC Public Reading Room is located in the EPA Headquarters Library,
Room Number 3334 in the EPA West Building, located at 1301 Constitution
Ave., NW., Washington, DC. The hours of operation are 8:30 a.m. to 4:30
p.m. Eastern Time, Monday through Friday, excluding Federal holidays.
Please contact (202) 566-1744 or e-mail the ORD Docket at   HYPERLINK
"mailto:ord.docket@epa.gov"  ord.docket@epa.gov  for instructions.
Updates to Public Reading Room access are available on the Web site ( 
HYPERLINK
"http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html
&log=linklog&to=http://www.epa.gov/epahome/dockets.htm" 
http://www.epa.gov/epahome/dockets.htm ).

	The June 27-29, 2007 draft HSRB meeting draft report is now available.
You may obtain electronic copies of this document, and certain other
related documents that might be available electronically at
www.regulations.gov and the EPA HSRB Web site at   HYPERLINK
"http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html
&log=linklog&to=http://www.epa.gov/osa/hsrb/" 
http://www.epa.gov/osa/hsrb/ . For questions on document availability or
if you do not have access to the Internet, consult the person listed
under FOR FURTHER INFORMATION CONTACT.

C. What Should I Consider as I Prepare My Comments for EPA?

	You may find the following suggestions helpful for preparing your
comments:

	1. Explain your views as clearly as possible.

	2. Describe any assumptions that you used.

	3. Provide copies of any technical information and/or data you used
that support your views.

	4. Provide specific examples to illustrate your concerns.

	5. To ensure proper receipt by EPA, be sure to identify the docket ID
number assigned to this action in the subject line on the first page of
your response. You may also provide the name, date, and Federal Register
citation.

D. How May I Participate in This Meeting?

	You may participate in this meeting by following the instructions in
this section. To ensure proper receipt by EPA, it is imperative that you
identify docket ID number EPA-HQ-ORD-2007-0403 in the subject line on
the first page of your request.

	1. Oral comments. Requests to present oral comments will be accepted up
to November 6, 2007. To the extent that time permits, interested persons
who have not pre-registered may be permitted by the Chair of the HSRB to
present oral comments at the meeting. Each individual or group wishing
to make brief oral comments to the HSRB is strongly advised to submit
their request (preferably via e-mail) to the person listed under FOR
FURTHER INFORMATION CONTACT no later than noon, Eastern time, November
6, 2007, in order to be included on the meeting agenda and to provide
sufficient time for the HSRB Chair and HSRB DFO to review the meeting
agenda to provide an appropriate public comment period. The request
should identify the name of the individual making the presentation and
the organization (if any) the individual will represent. Oral comments
before the HSRB are limited to 5 minutes per individual or organization.
Please note that this includes all individuals appearing either as part
of, or on behalf of an organization. While it is our intent to hear a
full range of oral comments on the science and ethics issues under
discussion, it is not our intent to permit organizations to expand these
time limitations by having numerous individuals sign up separately to
speak on their behalf. If additional time is available, there may be
flexibility in time for public comments.

	2. Written comments. Although you may submit written comments at any
time, for the HSRB to have the best opportunity to review and consider
your comments as it deliberates on its report, you should submit your
comments at least 5 business days prior to the beginning of this
teleconference. If you submit comments after this date, those comments
will be provided to the Board members, but you should recognize that the
Board members may not have adequate time to consider those comments
prior to making a decision. Thus, if you plan to submit written
comments, the Agency strongly encourages you to submit such comments no
later than noon, Eastern Time, November 6, 2007. You should submit your
comments using the instructions in Unit 1.C. of this notice. In
addition, the Agency also requests that person(s) submitting comments
directly to the docket also provide a copy of their comments to the
person listed under FOR FURTHER INFORMATION CONTACT. There is no limit
on the length of written comments for consideration by the HSRB.

E. Background

	The EPA Human Studies Review Board will be reviewing its draft report
from the June 27-29, 2007 HSRB meeting. Background on the June 27-29,
2007 HSRB meeting can be found at 72 FR 31323 (June 6, 2007) and at the
EPA HSRB Web site   HYPERLINK "http://www.epa.gov/osa/hsrb/" 
http://www.epa.gov/osa/hsrb/ . The Board may also discuss planning for
future HSRB meetings.

Dated: October 18, 2007.

Elizabeth Lee Hofmann,

Deputy Director, Office of the Science Advisor.

[FR Doc. E7-20953 Filed 10-23-07; 8:45 am]

BILLING CODE 6560-50-P

Attachment C

11/7/07 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

HUMAN STUDIES REVIEW BOARD (HSRB) 

PUBLIC TELECONFERENCE MEETING 

NOVEMBER 13, 2007 

1:00 pm -3:00 pm (Eastern Time) 

HSRB MEETING FOR REVIEW AND APPROVAL OF 

DRAFT JUNE 27-29, 2007 HSRB MEETING REPORT * 

HSRB WEB SITE http://www.epa.gov/osa/hsrb/ 

Docket Telephone: (202) 566-1752 

Docket Number: EPA-HQ-ORD-2007-0403 

Meeting location via telephone only 

Members of the public may obtain the call in number at (202) 564-5275 

1:00 PM	Introduction and Identification of Board Members – Celia
Fisher, Ph.D. (HSRB Chair) 

1:10 PM 	Meeting Administrative Procedures – Paul Lewis, Ph.D.
(Designated Federal Officer, HSRB, OSA, EPA) 

1:15 PM 	Meeting Process – Celia Fisher, Ph.D. (HSRB Chair) 

1:20 PM 	Public Comments 

1:30 PM 	Board Discussions and Decision on Report – Celia Fisher,
Ph.D. (HSRB Chair) 

A. 	Proposed Carroll-Loye Picaridin Insect Repellent Efficacy Study
LNX-001 

1.	If the proposed research described in Protocol LNX-001 from
Carroll-Loye Biological Research is revised as suggested in EPA’s
review, does the research appear likely to generate scientifically
reliable data, useful for assessing the efficacy of the test substances
for repelling mosquitoes? 

2.	If the proposed research described in Protocol LNX-001 from
Carroll-Loye Biological Research is revised as suggested in EPA’s
review, does the research appear to meet the applicable requirements of
40 CFR part 26, subparts K and L? 

B.	Proposed ICR Picaridin Insect Repellent Efficacy Study 

1.	If the proposed research described in ICR’s proposed picaridin
protocol is revised as suggested in EPA’s review, does the research
appear likely to generate scientifically reliable data, useful for
assessing the efficacy of the test substances for repelling mosquitoes? 

2.	If the proposed research described in ICR’s proposed picaridin
protocol is revised as suggested in EPA’s review, does the research
appear to meet the applicable requirements of 40 CFR part 26, subparts K
and L? 

C. 	Completed Inhalation Study with Acrolein 

1.	Please comment on whether the study is sufficiently sound, from a
scientific perspective, to be used to estimate a safe level of acute
inhalation exposure to acrolein.

2. 	Please comment on the following: 

a) 	Is there clear and convincing evidence that the conduct of the study
was fundamentally unethical? 

b)	Is there clear and convincing evidence that the conduct of the study
was significantly deficient relative to the ethical standards prevailing
at the time the research was conducted? 

D. 	Completed Studies on the Therapeutic and non-Therapeutic Effects of
Administration of 4-aminopyridine 

1. 	Please comment on whether the studies are sufficiently sound, from a
scientific perspective, to be used to derive a point of departure for
estimating risk to humans from exposure to 4-AP. 

2.	Please comment on the following: 

a) 	Is there clear and convincing evidence that the conduct of any of
the three clinical studies (Segal et al., 1999; Grijalva et al., 2003;
Van Diemen et al., 1993) was fundamentally unethical? 

b) 	Is there clear and convincing evidence that the conduct of any of
the clinical studies was significantly deficient relative to the ethical
standards prevailing at the time the research was conducted? 

E. Design of Research on the Levels of Exposure Received by Pesticide
Handlers 

Risks and Benefits of Handler Research 

Will the Task Forces’ Governing Documents considered in conjunction
with the additional study- and scenario-specific information specified
above provide an adequate basis for assessing whether the risks of
conducting a particular study are justified by the expected benefits of
the proposed research? If not, what additional information should be
provided for an IRB, EPA, and the HSRB? 

Addressing Potential Sources of Underestimation Bias 

1. 	Has EPA appropriately characterized the limitations on the
scientific usefulness of a handler database that does not include data
characterizing the efficiency of residue removal procedures? If not,
what limitations have been overlooked? 

2. 	Has EPA identified the relevant scientific and practical
considerations affecting the choice to include biomonitoring, and has
EPA appropriately characterized the limitations on the scientific
usefulness of the resulting data if no biomonitoring is conducted? If
not, what other considerations should bear on a decision to conduct
biomonitoring in addition to WBD? 

QA and QC Controls 

Do the Task Forces’ Standard Operating Procedures appear adequate to
ensure that the data resulting from the proposed research will be of
high quality? If not, what other Quality Assurance or Quality Control
procedures need to be addressed? 

Design of scenario-level sampling strategies 

With regard to the AHETF and AEATF plans to conduct their proposed
handler research using purposive diversity sampling strategies: 

1. 	Has EPA identified the relevant scientific and practical
considerations affecting the choice of a strategy for sample selection?
If not, what other considerations should bear on the choice? 

2. 	Does the HSRB agree with EPA that the Task Forces should provide
scenario-specific information about the availability of data to identify
significant variables (other than AaiH) potentially influencing exposure
and about the feasibility of developing a sampling strategy to address
those variables quantitatively? If not, what additional information is
needed? 

3.	Has EPA appropriately characterized the limitations on the scientific
usefulness of the resulting data attributable to the choice of the
sampling strategy? If not, what has EPA overlooked? 

Statistical justification for number of clusters and monitoring units 

What additional information, if any, would the HSRB need to assess the
adequacy of the justification for the number of clusters and number of
MUs in specific AHETF and AEATF study proposals? 

Within-Worker variability 

Has EPA appropriately characterized the limitations on the scientific
usefulness of a database that does not include repeated measures? If
not, what limitations has EPA overlooked? 

Subject recruitment and enrollment issues 

Does the Board agree that the Governing Documents and associated SOPs of
the AHETF and AEATF research programs include comprehensive and
appropriate protections for human subjects of the research? If not, what
has been overlooked?

 

In singling out the handling of language differences as an area
requiring further refinement, has EPA overlooked other areas in need of
revision? If so, what? 

2:45 PM	Summary and Next Steps – Celia Fisher, Ph.D. (HSRB Chair) and
Paul Lewis, Ph.D. (Designated Federal Officer, HSRB, EPA) 

3:00 PM 	Adjournment 

*Please be advised that agenda times are approximate. For further
information, please contact the 

Designated Federal Officer for this meeting, Crystal Rodgers-Jenkins via
telephone: (202) 564-5275 or e-mail: rodgers-jenkins.crystal@epa.gov. 

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