October 6, 2008

MEMORANDUM

SUBJECT:	Draft Final Report from the Human Studies Review Board on the
June 2008 Meeting 

TO:		Paul I. Lewis, Ph.D. 

		Designated Federal Official

		Human Studies Review Board

		Office of Science Advisor (8105R)

FROM:	William L. Jordan 

		Senior Policy Adviser 

		Office of Pesticide Programs (7501P)

This memorandum offers comments from the Office of Pesticide Programs
(OPP) on the draft Final Report from the Human Studies Review Board
(HSRB or Board) on its June 24-25, 2008, meeting.  The draft report
covered two topics: (1) proposals from the Agricultural Handlers
Exposure Task Force (AHETF) for two pesticide applicator exposure
monitoring studies under the closed-cab airblast scenario and (2) the
completed Insect Control and Research (ICR) mosquito repellent efficacy
study A117.

OPP has no comments on the Board’s advice concerning ICR study A117.

OPP offers the following observations with respect to the Board’s
advice concerning the research proposals submitted by the AHETF for
measuring handler exposure while applying liquid pesticide sprays using
conventional airblast equipment drawn by closed-cab vehicles.  Our
comments focus particularly on the HSRB’s recommendations to change
the sampling strategy and expand the sample size to produce more
scientifically useful data.  Unlike OPP’s previous reviews of draft
HSRB reports, these comments do not contain specific editorial
suggestions; rather our concern is with clarifying the overall thrust of
the Board’s recommendations about the AHETF proposals.  

The design of the AHETF’s sampling strategy has drawn comments in
previous HSRB meetings in June 2006, April 2007, and June 2007. 
Generally the Board has recommended that the exposure research employ a
probability-based sampling strategy so that the results would be
statistically representative of the population exposures that EPA will
be assessing when EPA performs risk assessments using these data.  The
Board has repeatedly stressed the limitations of any data collected on
research participants selected by a purposive sampling strategy, such as
that proposed by the AHETF.  In its draft Final Report the Board
continues to recommend that the AHETF change its sampling strategy and
expand the sample size.

The concerns raised by the HSRB in the earlier meetings cited above led
OPP to reconsider its position on what sampling methodologies to accept.
 As we explained in our presentations at the June meeting, we spent
nearly two years in discussions with the AHETF and with internal and
external experts before reaching a decision on this issue.  We carefully
weighed the factors relevant to assessing alternative sampling designs
– the feasibility and cost of different sampling methods; the
scientific value of the resulting data sets; and our intended use of the
datasets.  Fully appreciating the Board’s position on the importance
of obtaining statistically representative data, OPP has nonetheless
decided to accept data from the AHETF’s proposed purposive sampling
design.  In our professional judgment the data generated by the AHETF
research will provide scientifically reliable measurements of individual
participants’ exposures and, when used together with other information
on potential exposure available to the Agency, will support estimates of
high-end handler exposures. 

Dr. Debra Edwards, Director of OPP, announced and explained this
decision to the Board at the June meeting.  She told the Board that we
regard the AHETF’s proposed research – including its proposal to use
a purposive sampling strategy – to be scientifically sound.  She
acknowledged plainly the limitations on use of the resulting data; she
also noted that the new data would represent a great improvement over
existing data, both qualitatively and quantitatively, and would be
adequate for our regulatory purposes.  She told the Board that she
believes getting the new data is important to improve our assessments of
handler exposure to pesticides.  OPP has been and remains eager for the
AHETF to perform this research.  

We were not surprised when, at the June meeting, the HSRB again
commented critically on the AHETF sampling strategy.  We listened
closely to the Board’s discussions of the AHETF proposals, and our
overall impression was that, although the Board would prefer a research
program of a different kind, the HSRB understood and accepted OPP’s
decision.  The minutes of the June meeting, certified by Dr. Fisher,
reinforce this impression:

[Dr. Fenske] stated that the research is likely to generate
scientifically sound data that will be useful for EPA risk assessment
activities.  He commended the Agency’s evaluation and presentation of
the materials and the Task Force for addressing most of EPA’s concerns
in its June 13, 2008 letter. 

[p. 33]

 Dr. Johnson agreed that the data would be scientifically reliable and
will be useful for assessing exposure.  He agreed with Dr. Edwards that
EPA needs this data for its risk assessment activities because existing
data are inadequate. 

[p. 35]

Overall, the Board was impressed by the design of the research. The
Board questions the usefulness of the data and cautions EPA against use
of the data for other than the intended purpose. It is difficult to
conclude that the data will be “reliable” because of the lack of
replicate measures; however, the protocol will collect sound qualitative
data that will be useful to EPA.  

[From Dr. Fisher’s summary of the Board discussion, p. 37]

In sum, what we heard from the Board during the June 2008 meeting did
not seem to challenge our decision, and did not lead us to change our
views.  In early July, we advised the AHETF to proceed with their
research after making certain revisions to their protocols; they have
done so.

In view of this history, we were surprised and confused by the
discussion of the AHETF sampling strategy in the HSRB’s draft Final
Report.  In its summary introduction the draft states:

If the approach presented in these protocols were adopted, then the
sample size would need to be increased. 

(p. 1)

and 

In conclusion, if the AHETF materials are revised in accordance with the
Agency’s suggestions and the Board’s recommendations, including
implementation of the Board’s recommended alternative design, several
limitations with the proposed research will be alleviated and the
research is more likely to generate scientifically reliable data, useful
for assessing the exposure of handlers who apply liquid pesticides using
airblast equipment drawn by vehicles with closed cabs. 

(p. 2, emphasis added) 

The draft Final Report presented detailed recommendations for what would
amount to a major change in the design of the sampling strategy (pp.
12-13), and then added:

Finally the Board urged the Agency to seriously consider the alternative
design presented earlier in this report before making a final decision
on study design. (p. 15)

The sense of the draft final report and the minutes of the meeting are
different.  While the minutes mention ways to improve the AHETF study
design, the minutes do not indicate that such changes were a
prerequisite to generating scientifically valid results.  In fact, the
generally favorable summary statements quoted from the minutes of the
meeting were not conditioned on a substantial change to the proposed
design of the research, and the Board did not discuss such a condition
in June.  In contrast, the draft Final Report seems to indicate that the
Board would not consider data generated by the proposed AHTETF protocols
to be scientifically useful unless the design had changed
significantly..  

If the Board is only advising EPA to encourage the handler exposure task
forces to consider sampling strategies that would generate statistically
representative data, we do not disagree that data developed using a
different method could have broader scientific utility than data derived
using different sampling methods.  But, as Dr. Edwards explained, the
issue for EPA and the HSRB is not whether the research could be better;
the issue is whether the research, as proposed, is likely to generate
valid data useful for OPP’s regulatory purposes.  We think that the
AHETF proposals meet that standard, and we believe the Board agrees.  We
hope the Board will clarify its views.

