10/22/07 DRAFT

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

HUMAN STUDIES REVIEW BOARD (HSRB)

OCTOBER 24-26, 2007 

PUBLIC MEETING

Wednesday, October 24, 2007

Environmental Protection Agency 

Conference Center - Lobby Level 

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive

 Arlington, VA 22202 

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

Docket Telephone: (202) 566 1752

Docket Number: EPA-HQ-ORD-2007-0942

( 8:30 AM	Convene Meeting and Identification of Board Members – Celia
Fisher, Ph.D. (HSRB Chair)

( 8:40 AM	Welcome – George Gray, Ph.D. (EPA Science Advisor) 

( 8:45 AM	Opening Remarks – Debbie Edwards, Ph.D. (Director, Office of
Pesticide Programs, [OPP])

( 8:50 AM	Meeting Administrative Procedures - Paul Lewis, Ph.D.
(Designated Federal Officer [DFO], HSRB, OSA, EPA) 

( 8:55 AM	EPA Follow-up on HSRB Recommendations – Mr. William Jordan
(EPA, OPP)   

Scientific and Ethical Approaches for Observational Exposure Studies 

( 9:05 AM	EPA Draft Document Scientific and Ethical Approaches for
Observational Exposure Studies– Roy Fortmann, Ph.D. and Larry Cupitt,
Ph.D. (Office of Research and Development, EPA)   

( 10:15 AM	Break    

( 10:30 AM	Public Comments

( 11:00 AM	Board Discussion   

One of the goals of the document is identify the major scientific and
ethical areas and issues that researchers should address in the design
and implementation of observational human exposure measurement studies,
with the emphasis on the areas requiring ethical considerations.  Does
each section identify the major areas and issues where ethical
considerations should be addressed?

( 12:15 PM	Lunch   

( 1:00 PM	Board Discussion (continued)  

The document is intended to serve as a reference and resource of
information that researchers can use in the design and implementation of
observational exposure studies.  Are there additional sources of
information that should be considered for inclusion in the section?

Is the information presented accurately and clearly in each section?

Note: Board discussion will focus on responding to the three charge
questions together by  section (Sections 1 to 7) of the EPA draft
document 

Sodium Azide 

( 1:45 PM	Science and Ethics of Sodium Azide Study – Ms. Nancy
McCarroll (OPP, EPA) and Mr. John Carley (OPP, EPA)  

( 2:30 PM	Public Comments 

( 2:45 PM	Board Discussion      

The Agency has concluded that this study contains information sufficient
for assessing human risk resulting from potential acute and chronic
exposure.  Please comment on whether the study is sufficiently sound,
from a scientific perspective, to be used to estimate a safe level of
acute and chronic exposure to sodium azide.  

Please comment on the following:

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

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?

( 3:30 PM	Adjournment   

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

HUMAN STUDIES REVIEW BOARD (HSRB)

OCTOBER 24-26, 2007 *

PUBLIC MEETING

Thursday, October 25, 2007

Environmental Protection Agency 

Conference Center - Lobby Level 

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive

 Arlington, VA 22202 

( 8:00 AM	Convene Meeting –  Celia Fisher, Ph.D. (HSRB Chair)

( 8:05 AM	Follow-up From Previous Day’s Discussion – Mr. William
Jordan (OPP, EPA)  

Science Issues in Mosquito Repellent Efficacy Field Research 

( 8:10 AM	Introduction – Celia Fisher, Ph.D. (HSRB Chair)

( 8:20 AM	EPA Presentation -   Mr. William Jordan (EPA, OPP)   

( 8:40 AM	Public Comments

( 8:55 AM	Board Discussion   

Issue 1.

	What do data show about the variability of the time intervals
between first and subsequent landings in mosquito repellent field
trials?

	What is the current scientific understanding of how factors other
than repellent efficacy could affect the likelihood that an initial
event—a mosquito landing or mosquito bite—would be “confirmed”
by another similar event within 30 minutes?  Please address at least
these factors:

o	Characteristics of mosquito populations

o	Characteristics of test sites

o	Characteristics of test subjects

o	Characteristics of test methods

	Can the impact of such factors on the likelihood or timing of an
initial and confirming event be predicted?  Can it be quantified?   

Issue 2.  

At its June 27 - 29, 2007 meeting the Board learned that different
designs with different “length-biased” sampling for mosquito
repellent field studies are in use.  One design exposes subjects to
potential mosquito landings for one minute of every 15 minutes; another
design exposes subjects to potential mosquito landings for five minutes
of every 30 minutes. 
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	What is the methodological rationale for the two different designs? 

	Which design is used more widely in the field? Why? 

	Can potential effects of variation in the pattern of intermittent
exposure on the results of efficacy testing be isolated from the effects
of other variables?  If so, can the direction or magnitude of the
effects be predicted?  How might these influences be analyzed and
accounted for in collecting, reporting and analyzing repellent efficacy
data?

Issue 3. 

Dr. Matt Kramer, a USDA statistician who has served as a consultant, has
suggested that the precision of estimates of Complete Protection Time
(CPT) in repellent testing could be significantly increased by defining
a failure of efficacy as the mean time from treatment to a series of
several landings or bites.  He has stated:

The precision of CPT increases when it is estimated beyond time to
[First Confirmed Bite] FCB or FCLanding.  How well CPT can be estimated
depends on the distribution of so many bites beyond FCB.  The number of
mosquitoes that will bite (n) will determine results of the test.  Each
person in the field should be his/her own control; that way it is
possible to know n per person, and reduce person-to-person variability.

If using the mean time to the first 5 bites, the SE will decrease
proportionally as n increases (n = 5 in this case).  That is equivalent
to an increase in the power of the test of 5 times.  This method allows
for detecting formulation differences near the CPT.

	Does this approach, indeed, increase the precision of estimates of
CPT markedly without requiring additional subjects?

	If so, would this increased precision justify the incremental risk
to the subjects resulting from their exposure to a great?

Is it practical to test long-lasting repellents to the point of five
landings?

( 10:00 AM	Break   

( 10:15 AM	Board Discussion (continued)   

Completed Field Efficacy Studies by Carroll-Loye Biological Research:
SCI-001 and WPC-001

( 11:15 AM	EPA Science and Ethics of Completed Carroll-Loye Biological
Research Studies SCI-001 and WPC-001 – Clara Fuentes, Ph..D. (OPP,
EPA), Mr. Kevin Sweeney (OPP, EPA) and Mr. John Carley (OPP, EPA)  

( 12:15 PM	Lunch   

( 1:15 PM	Public Comments   

( 1:45 PM	Board Discussion 

SCI-001

Is this study sufficiently sound, from a scientific perspective, to be
used to assess the repellent efficacy of the formulations tested against
mosquitoes?  Please comment specifically on:

Whether participation in field testing by several subjects on the day
after they had been treated with a different test repellent is likely to
have affected the validity of the results for those subjects on those
days.  

The effects of changes to the experimental design resulting in
evaluation of repellents using fewer than ten subjects per treatment per
day, followed by pooling of results by site for statistical analysis.

Does available information support a determination that this study was
conducted in substantial compliance with subparts K and L of EPA
regulations at 40 CFR part 26?  Please comment specifically on:

The decision to use a different test formulation in place of one of the
test materials described in the protocol reviewed by the IRB, EPA and
the HSRB.

How to assess the ethical conduct of an insect repellency study
involving multiple test formulations when there is an ethical deficiency
in the conduct of the study with respect to one of the test
formulations.  If the ethical deficiency warrants not relying on the
results of the testing with regard to one test formulation, under what
circumstances (if any) does the ethical deficiency affect the
acceptability of the results from testing the other formulations?  

WPC-001

Is the research conducted under WPC-001 sufficiently sound, from a
scientific perspective, to be used to assess the repellent efficacy of
the formulation tested against mosquitoes?  Please comment specifically
on whether participation in field testing by several subjects on the day
after  they had been treated with a different test repellent is likely
to have affected the validity of the results for those subjects on those
days.

Does available information support a determination that the research
covered by WPC-001 was conducted in substantial compliance with subparts
K and L of EPA regulations at 40 CFR part 26?  If the conduct of any
part of SCI-001 is deemed not to substantially comply with the
requirements of subparts K and L, please comment specifically on how to
assess the ethical conduct of research conducted under WPC-001 in light
of the fact that it was conducted at the same times and at the same
places as the research covered under protocol SCI-001.  

( 3:00 PM	Break   

Carroll-Loye Biological Research Insect Repellent Efficacy Protocols

SPC-001

( 3:15 PM	Science and Ethics of Carroll-Loye Protocol SPC-001 – Mr.
Kevin Sweeney (OPP, EPA) and Mr. John Carley (OPP, EPA)  

( 3:45 PM	Public Comments  

( 4:00 PM	Board Discussion 

If the proposed research described in Protocol SPC-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? 

If the proposed research described in Protocol SPC-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?  

SPC-002

( 5:00 PM	Science and Ethics of Carroll-Loye Protocol SPC-002 – Mr.
Kevin Sweeney (OPP, EPA) and Mr. John Carley (OPP, EPA)  

( 5:30 PM	Public Comments   

( 5:45 PM	Board Discussion   

If the proposed research described in Protocol SPC-002 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? 

If the proposed research described in Protocol SPC-002 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?  

( 6:45 PM	Adjournment  

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

HUMAN STUDIES REVIEW BOARD (HSRB)

OCTOBER 24-26, 2007 *

PUBLIC MEETING

Friday, October 26, 2007

Environmental Protection Agency 

Conference Center - Lobby Level 

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive

 Arlington, VA 22202 

( 8:30 AM	Convene Meeting –  Celia Fisher, Ph.D. (HSRB Chair)

( 8:35 AM	Follow-up From Previous Day’s Discussion – Mr. William
Jordan (OPP, EPA)  

ICR Repellency Efficacy Protocol   A117

( 8:40 AM	EPA Science and Ethics Reviews of ICR Protocol A117– Mr.
Kevin Sweeney (OPP, EPA) and Mr. John Carley (OPP, EPA) 

( 9:15 AM	Public Comments 

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Board Discussion 

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
of the genus Culex? 

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?  

( 10:30 AM	Break  

EPA Update of AEATF and AHETF Research Programs

( 10:45 AM	EPA Presentation -   William Jordan (OPP, EPA)

( 11:00 AM	Public Comments   

( 11:15 AM	Board Discussion 

No Board Charge

( 12:30 PM	Adjournment - Celia Fisher, Ph.D. (HSRB Chair) and Paul
Lewis, Ph.D. (DFO, HSRB, OSA, EPA) 

* Please be advised that agenda times are approximate and subject to
change. For further information, please contact the Designated Federal
Officer for this meeting, Paul Lewis via telephone: (202) 564-8381 or
email:   HYPERLINK "mailto:lewis.paul@epa.gov"  lewis.paul@epa.gov  

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