will be assessed; merely asking a participant if they are literate is
insufficient.  Spanish speakers should be available at all telephone
numbers that potential subjects are instructed to call for further
information, including those listed on the ICFs and for the IRB.  The
means by which subject understanding of the research will be assessed is
unclear; a quiz with suggested answers is provided in the appendix but
it is not clear if this will be used for all subjects.  The protocol
does not describe how persons conducting the consent interviews are
trained to assess subject understanding.  The background risk of
agricultural work should not be used when assessing the risk-benefit
relationship.  The Task Force should consider offering risk counseling
related to working with pesticides while pregnant to subjects who have a
positive pregnancy test; handouts or a referral would suffice.  The Task
Force also should consider obscuring participants’ identities in
photographs and video footage.  There is no discussion of the expected
gender distribution of applicators on the IIRB application.  The
predicted ethnicity distribution is 90 percent White and 10 percent
Hispanic in Florida and Georgia, which seems to be a low amount of
Hispanic participants.

The protocol states that the documents of those who withdraw from the
study because of a positive pregnancy test will be destroyed; EPA must
indicate whether this is acceptable.  References to interpreters and
witnesses should be removed from the documentation and SOPs for this
protocol because the Task Force has decided instead to use bilingual
researchers.  The ICF states that compensation for research-related
injuries will cover the cost of “reasonable and appropriate” medical
treatment; this phrase should be removed.  Dr. Fish agreed with
Mr. Carley’s suggestion to list certain procedures in the SOP rather
than the protocol because of inconsistencies between descriptions in the
SOP and the protocol.  SOP 11.F.0 for adverse event reporting states
that adverse events will be reported to Western IRB.  This languages
needs to be changed because adverse events should be reported to IIRB.
The ICF refers only to the AHETF and not to the sponsor; at this point,
a re-write is not necessary but should be considered in the future.  The
Spanish translation of the recruitment poster states that subjects are
not qualified if they are “cognitively impaired;” this language
should be simplified.  If these changes are made, the protocol meets the
ethics charge question.

Dr. Chadwick noted that the section discussing use of photographs in the
ICF borders on exculpatory.  The document states that the AHETF owns the
rights to photographs and can use them for any purpose.  This asks
participants to waive rights that are unrelated to the research.  There
are ways to document the research using photographs that do not identify
the subjects.  The ICF should discuss the need for and use of the
photographs.  Dr. Menikoff agreed that the AHETF should clarify how the
photographs can and will be used.  Assuming appropriate limitations on
use, it is reasonable to not obscure identities at all times.  These
situations are not as embarrassing as typical medical photographs.  The
ICF states that subjects will not be photographed while dressing;
expanding the explanation of use of the photographs should be
sufficient.

Dr. Prentice inquired why the charge questions ask if the research
“appears” likely to generate reliable data and if EPA’s use of the
word “appear” in the charge questions was deliberate.  Mr. Jordan
explained that the use of “appear” was intended to convey that
despite the best plans, in practice the research may not comport with
standards.  EPA uses the charge question to determine that if a protocol
is performed as described, subjects will most likely be treated
ethically.  Dr. Fisher reminded Board members that the HSRB is not an
IRB.  The HSRB makes recommendations to EPA to ask for further
information or modifications to a protocol.  The protocol may return to
an IRB after Board review.

Dr. Prentice stated that he largely agreed with other Board reviewers
regarding the ethics charge questions.  He noted that there was some
confusion about when potential subjects receive a copy of the ICF.  It
appears that consenting may occur several days before or up to the day
of the study.  Volunteers should receive a copy of the ICF at least 1
day before the study.  Mr. Carley explained that subjects probably
receive the ICF at the initial group meeting and then can schedule
individual interviews; however, EPA will check that this is clarified.
Dr. Prentice expressed concern about the payment of $20 to participants
who attend an interview, whether or not they participate in the
research.  Dr. Fish explained that this was usual practice at her
institution; the nominal payment is intended to cover the costs of
transportation and child or other dependent care.

Dr. Parkin noted that obscuring the identity of participants was
important not only for reasons of potential embarrassment but also to
protect undocumented participants.  She stated that she also was
uncomfortable with IIRB both translating and approving the translated
materials.  Dr. Menikoff asked if undocumented workers were a specific
concern, because the study design appears to make it unlikely that
undocumented workers will enroll in these studies.  Mr. Carley explained
that the anti-microbial exposure research taking place in California
required proof of age using a government-issued photograph
identification form that was not issued to illegal residents.  This
protocol also requires a government-issued form of identification and
thus illegal workers are unlikely to enroll.  Dr. Carriquiry noted that
the ICF does not specify that the identification must be issued by the
United States government.

Concerning translation by the IRB, Dr. Chadwick remarked that the IRB he
works with will obtain a translation of a document for an investigator,
but the process by which this is done was not known.  Dr. Fish explained
that commercial IRBs often have Spanish-speaking translators on staff.
She added that using IRB staff members to translate documents is
preferable because they understand the information that needs to be in
the form and the degree of clarity required.  Dr. Fisher asked if EPA
agreed with the AHETF’s decision to destroy the records of women who
have a positive pregnancy test.  Mr. Carley explained that EPA expects
these women to be included in counts of interview participants, but
agreed with the decision to destroy their information.  Dr. Chadwick
noted that testing for literacy was not a requirement for participation
in this protocol.  Dr. Sean Philpott stated that the ICF as written is
too complex for the target population and should be simplified.

Dr. Fisher summarized that the protocol meets the requirements of 40 CFR
part 26, subparts K and L with some changes and recommendations.  The
AHETF should ensure that its test for understandability is objective and
should train interviewers in assessing understanding.  All forms need to
list Spanish speakers who can be contacted by potential subjects.
Destroying the records of pregnant subjects is acceptable.  Regarding
photographs, any exculpatory language in the ICF should be removed.  Use
of films should be described in the ICF and restricted in their use
(i.e., used only for research or training purposes).  Task Force
observers should strive to avoid taking pictures of participants’
faces or should work to obscure their identity.  The Task Force did not
provide data on gender distribution and the expected ethnic distribution
(90 percent White and 10 percent Hispanic) was surprising; the AHETF
should describe the reasons for this distribution.  The reference to use
of interpreters and witnesses should be modified.  The phrase
“reasonable and appropriate” should be removed from the provision
for medical treatment.  Inconsistencies between the protocol and the SOP
should be resolved; most of this information can be described in the SOP
and referred to in the protocol.  Clarification of adverse event
reporting to the appropriate IRB is needed.  The recruitment poster
should list a Spanish-speaking contact and a local contact.
Clarification of when consent is obtained is needed.

Dr. Prentice inquired about training of informed consent interviewers.
Dr. Fish responded that no information was provided concerning how the
consent interview should proceed.  The documents mention standard
Collaborative IRB Training Initiative or National Institutes of Health
(NIH) procedures.  Dr. Prentice said that the Task Force should consider
including culturally relevant training.  Dr. Carriquiry remarked that
the Spanish version of the documents is inaccurate; the Spanish version
does not state that participation is voluntary until quite late in the
document.  Clarification that participation is voluntary is needed.  In
response to suggestions to obtain a back translation of the documents,
Dr. Fish explained that many interpreters find this inadequate and
prefer use of a certified translator to ensure that the language is
appropriate and culturally suitable.

Review of April 9-10, 2008 HSRB Meeting Report

Review Process

Dr. Lewis stated that the Board would review for subsequent approval of
its report for the April 9-10, 2008 HSRB meeting.

Public Comments

	Dr. Lewis invited oral public comment on the draft April 9-10, 2008
HSRB meeting report.  No oral public comments were presented.

Board Discussion and Decision on Report

Dr. Fisher opened discussion on the draft report by asking if Board
members had any suggested changes to the Board Recommendations on Review
and Format on the AEATF and AHETF Protocols (overall recommendations,
format of the protocols for subsequent HSRB review, format of Agency
presentations, and Task Force comments at the meeting) (p. 15, lines
25-45 and p. 16, lines 1-38).  No comments or changes were made.

Regarding the HSRB Consensus and Rationale related to scientific
considerations for the AEATF-II study protocols (p. 21, lines 42-46 and
p. 22, lines 1-36), no comments were made.  No comments were made for
the HSRB Consensus and Rationale related to ethical considerations (p.
26, lines 43-46 and p. 27, lines 1-2).

No comments were made for the HSRB Consensus and Rationale related to
scientific considerations for the protocol ICR A382 (p. 28, lines
30-36), studying the efficacy of two formulations of picaridin for
repelling stable flies.  The Board also had no further comments on the
HSRB Consensus and Rationale related to ethical considerations (p. 30,
lines 15-19).

The Board had no further comments on the HSRB Consensus and Rationale
related to scientific considerations for Carroll-Loye Biological
Research Completed Studies SCI-001.4 and SCI-001.5 (p. 32, lines 4-9),
testing LipoDEET 302 and Coulston’s Duranon for repelling mosquitoes
in two field environments.  No comments were made regarding the HSRB
Consensus and Rationale related to ethical considerations for these
protocols (p. 35, lines 10-13).

The Board did not make changes to the section of the draft report
describing the Board’s decision regarding future review of protocols
with planned deviations from prior IRB review (p. 35, lines 15-46 and p.
36, lines 1-2).

Dr. Krishnan inquired if the overview on page 32 should be moved before
the science review in the report.  Dr. Philpott remarked that there is
some redundancy in the report regarding abstracts of the protocols, but
this will not occur in the future.  An abstract provided by EPA will be
included at the beginning of the review of a protocol, followed by the
science and ethics reviews.  The HSRB will review these abstracts to be
sure that issues the Board considers to be of importance are included.
Dr. Fisher agreed to eliminate the subheading on page 32, line 20.

Dr. Fisher asked each Board member to approve the changes discussed
during this meeting.  All Board members in attendance at the conclusion
of this discussion approved the report.  Dr. Lewis added he will make
any necessary grammatical changes to the report.

Follow-up from Previous Day’s Discussion

	Dr. Fisher summarized Board conclusions for the next AHETF submission.
The Board would like to see consideration of the recommendations it made
at this meeting.  In particular, an observer recording sheet describing
how worker behavior will be recorded should be included in information
provided to the Board, as should EPA’s analytic plan for its intended
use of the data.  It is difficult to determine if the 5x5 design will
provide useful data if the analytic plan is not included.  The plan can
be based on potential use as well as intended use.  EPA is welcome to
use consultants to develop its statistical approach.

EPA Review of Completed ICR Mosquito Repellent Efficacy Study A117

Background and Context

	Mr. Carley provided an overview of completed ICR mosquito repellent
efficacy study A117.  This study was a laboratory test of
already-registered repellent products for effectiveness against
mosquitoes of the genus Culex, a principal vector of West Nile Virus
(WNV).  The products were previously tested in the field against
mosquitoes of other genera.  Further testing was required by EPA to
support the proposed label claim to repel “mosquitoes which can vector
West Nile virus.”

	ICR protocol A117, submitted August 8, 2007, was reviewed favorably by
the HSRB in October 2007.  In early January 2008, ICR submitted a
revised protocol and ICF for informal EPA review, and met with EPA on
January 14, 2008, to discuss these documents.  On January 10, 2008,
the HSRB released the draft final report of its October 2007 meeting.
In February 2008, ICR further revised the protocol and consent form,
obtaining final IRB approval on February 26, 2008.  Laboratory testing
was conducted on March 4, 2008, and the final report of testing was
submitted to EPA on April 9, 2008.

	Because specific events occurring in February and early March 2008 were
of specific concern for the ethics review, Mr. Carley described this
time period in further detail.  On February 8, 2008, ICR further revised
the protocol and ICF, reflecting EPA and HSRB comments.  On February 14,
2008, ICR submitted the revised protocol and ICF to Essex IRB, Inc.
(EIRB).  EIRB reviewed and approved the February 8, 2008 protocol and
reviewed and conditionally approved the February 8, 2008 ICF, with calls
for numerous changes on February 18, 2008; however, none of these
changes were of substantive significance.  Most were minor editorial
changes and a few were requests for insertion of standard language.  ICR
began recruiting potential subjects on February 18, 2008.  On February
19, 2008, EIRB notified ICR by email of the results of its February 8,
2008 review.  On February 20, 2008, ICR submitted a further revised ICF
to EIRB, which EIRB approved on February 25, 2008.  EIRB notified ICR of
the approval on February 26, 2008.

	On April 9, 2008, ICR submitted its final report and supplement for
protocol A117 to EPA.  On May 19, 2008, EPA emailed a request for
clarification on three points:  the rationale for the change in dosing
regimen reported as a deviation from the protocol, the number of
subjects, and the sequence and timing of recruiting actions.  ToXcel
responded to EPA’s request for clarification on May 21, 2008.  EPA’s
science and ethics reviews were completed on May 22, 2008.  On June 6,
2008, toXcel responded to EPA’s reviews.

EPA Science Assessment of ICR Study A-117:  Laboratory Repellency of Two
Registered Picaridin Products to Culex Mosquitoes

	Mr. Mark Suarez (OPP, EPA) provided EPA’s science assessment of ICR
study A117.  The test materials were two registered repellents
containing 10 percent picaridin:  Avon Skin-So-Soft SSS Bug Guard Plus
Picaridin Insect Repellent (Lotion) (Reg No 806-29) and Avon
Skin-So-Soft SSS Bug Guard Plus Picaridin Insect Repellent (Spray) (Reg
No 806-31).  The study objectives were to determine the efficacy of the
repellents to Culex mosquitoes in the laboratory to support proposed
label claims for efficacy against “mosquitoes which can vector West
Nile virus,” based on the hypothesis that the repellent samples will
provide 8 hours of protection from Culex quinquefasciatus mosquitoes in
the laboratory.  Because the objectives of the study did not include
establishing a typical consumer dose, the dose used was the standard
1 gram per 600 square centimeters, for consistency with the dose used
in earlier testing of the same repellents.

	Based on the Rutledge and Gupta (1999) meta-analysis, a target sample
size of 10 was needed to establish a complete protection time (CPT) of 8
hours ± 2 hours with 95 percent confidence.  A total of 12 treated
subjects were planned, to ensure an N of 10 even with as many as two
drop-outs.  One untreated control subject was chosen by lot.  All 12
treated subjects completed testing; all results were included in the
analysis.

	The criticisms of the scientific design of this protocol in EPA’s
review of September 24, 2007, and in the HSRB’s final report of the
October 2007 meeting were satisfactorily addressed through the revisions
made to the protocol before it was executed.  These criticisms include
the following:

use of 200 mosquitoes per cage

expansion of the statistical analysis plan to include descriptions of
how to assess normality of distribution, how to analyze non-normal data,
and statistics for all contingencies

consideration of the Kaplan-Meier test in place of the Q test

designation of an endpoint as “CPT”

addition of a form for attractiveness data

appending the product labels to the protocol

clarification of the reference to “dose range finding”

extension of the test duration to 10 hours.

	Final revisions to the protocol were made on February 8, 2008.  The
revised protocol was approved by EIRB on February 18, 2008, and executed
on March 4, 2008.  The execution was generally consistent with the
protocol, with one reported deviation.  Instead of treating subjects in
six pairs, subjects were treated in two groups of six.  This deviation
did not affect the experimental outcomes, but should have been done by
protocol amendment rather than as a deviation.

	The cages used in this study were 2x2x2 foot cubes, sitting on a table.
 The floor of the cage is mirrored to enable observers to see mosquitoes
on the underside of the subjects’ arms.  The sides and top of the cage
are screen wire.  On two of the sides there are two fabric sleeves that
are secured around the upper forearms of the subjects with large rubber
bands.  Because there are two sets of sleeves, it was possible to test 2
subjects at once, each testing a different repellent on each forearm.

	Two hundred mosquitoes were released into each cage.  The mosquitoes
were laboratory-reared, disease-free adult (3- to 8–day-old) females
that had been fasted for 24 hours and had never received a blood meal.
Before subjects were treated with repellents, each subject established
attractiveness to the test mosquitoes by placing an untreated arm into
the mosquito-filled cage.  Once each subject had shown attractiveness to
mosquitoes, they were treated with one test repellent on each forearm
and testing began.  At 30-minute intervals, the untreated control
subject confirmed that the mosquitoes were still aggressive by putting
an untreated forearm into each cage.  If fewer than 5 mosquitoes landed
on the control subject’s arm within one minute, (as happened early in
the test), 200 fresh mosquitoes were added to each cage.  After the
aggressiveness of the mosquitoes was confirmed, treated subjects placed
their arms through the sleeves into the cage for 5 minutes.  This cycle
of confirmation of aggressiveness followed by 5-minute test exposures of
all treated subjects was repeated for 10 hours, or until a subject
experienced failure of efficacy on both arms, defined by a confirmed
bite on each treated arm.

	A failure of efficacy was defined as a “confirmed bite,” which was
one bite followed by another on the same arm within the same or the
subsequent 5-minute exposure period.  For test substance A, there were a
total of five bites (three unconfirmed and one confirmed).  For test
substance B, there were a total of six bites (two unconfirmed and two
confirmed).  CPT was defined as the time from treatment with the
repellent until the first confirmed bite, i.e., until the time of the
first bite confirmed by another (confirming) bite within the same or the
subsequent 5-minute exposure period.  CPTs were 9.417 ± 1.094 hours for
test substance A and 9.667 ± 0.421 hours for test substance B.  A
larger error was generated for substance A (lotion) because of an early
failure.

	EPA has concluded that the study provides scientific results that meet
EPA guideline standards, based on the study protocol as amended in
accordance with EPA and HSRB comments before testing began.  Both
products provided a CPT of approximately 9.5 hours against the WNV
vector Culex quinquefasciatus.

EPA Ethics Assessment of ICR Study A-117:  Laboratory Repellency of Two
Registered Picaridin Products to Culex Mosquitoes

	Mr. Carley provided EPA’s ethics assessment of protocol A117.
Documents considered in this review were the primary report of ICR Study
A117 (MRID 47397701) and supplemental information to address
requirements of 40 CFR (MRID 47413601).  Additional documents considered
were EPA’s protocol review of September 24, 2007, toXcel’s response
to the EPA protocol review (October 17, 2007), toXcel summary of a
January 14, 2008 meeting with EPA, the HSRB’s final report of its
October 2007 meeting (January 17, 2008), toXcel’s response to EPA’s
request for clarification (May 21, 2008), and toXcel’s further
clarification of recruiting events (received June 6, 2008).  The last
communication was not received until after this ethics review was
completed.

	Three deficiencies were noted.  The IRB minutes did not explain the
basis for requiring changes in the ICF.  The IRB roster did not indicate
members’ experience sufficient to describe their chief anticipated
contributions to deliberations and EIRB procedures were not submitted.
These gaps did not compromise EPA’s review.

	All comments from EPA and the HSRB were addressed in the revised
protocol and ICF of February 8, 2008.  These included the following:

revision of the discussions of risks and benefits in the protocol and
ICF

correction of the description of risk from repellents

addition of a discussion of environmental risks

discussion of risk of disease included in the ICF

addition of a description of attractiveness testing to the ICF

removal of the assertion that subjects are representative

justification or removal of the age cap at 55 years

adjusting ICF eligibility criteria to track with the protocol

clarification of descriptions of recruitment and consent processes

deletion of subject signature from data collection forms

harmonization of different discussions of control selection

clarification of how landing mosquitoes will be removed

	One protocol deviation was reported.  The protocol called for treating
subjects in six pairs; instead subjects were treated in two groups of
six.  The rationale provided was to simplify moving large numbers of
subjects in and out of the testing room.  EPA believes that this change
could have been anticipated and should have been made by amendment, with
prior IRB approval.  An unreported deviation involving initiation of
subject recruitment before final IRB approval of the ICF also occurred.

	On February 18, 2008, EIRB approved the February 8, 2008 protocol and
conditionally approved the ICF.  On February 18, 2008, the principal
investigator communicated with EIRB and was told that recruitment could
begin.  On February 18, 2008, ICR began calling previous subjects to
determine their interest and availability for the March 4, 2008 study.
On February 19, 2008, EIRB notified ICR by email of its decisions made
on February 18, 2008.  On February 20, 2008, ICR revised the ICF and
submitted it to EIRB.  EIRB approved the revised ICF on February 25,
2008 and notified ICR of its approval on February 26, 2008.  On
February 26, 2008, ICR mailed copies of the approved ICF to candidates
who had expressed interest in participating in the study.  The
communication with EIRB on February 18, 2008, and calling of subjects
occurring on the same date were reported in the June 6, 2008 report
from toXcel.

	Both EPA and the HSRB expressed concern about the recruiting process in
their reviews of ICR protocol A117, and called for its clarification.
The protocol description of the recruiting process was revised after the
October 2007 HSRB meeting to reflect EPA and HSRB comments.  The revised
protocol was approved by EIRB on February 18, 2008.  The recruiting
process initiated by ICR on February 18, 2008, and described in the
toXcel submissions dated May 22, 2008 and June 6, 2008, differed in
numerous respects from the process described in the revised protocol.

	Based on the toXcel submission of June 6, 2008, EIRB reportedly told
ICR on February 18, 2008 that “recruitment of study subjects could be
initiated since the protocol had been approved.”  However, no
documentation of the reported communication between the principal
investigator and EIRB personnel on February 18, 2008, has been provided.
 The June 3, 2008 email from EIRB on this matter does not mention any
prior communication on this subject.  Neither ICR nor toXcel has
reported, nor is there evidence of, any imminent hazard to subjects that
could have justified a change to approved research without prior IRB
approval.

	Based on its review, EPA has concluded that subjects were recruited
through a process differing from that prescribed in the protocol,
although this deviation from the protocol did not put subjects at
increased risk.  The subjects saw and signed the ICF only after final
IRB approval; therefore, the deviations from the protocol in the
recruitment process are unlikely to have seriously compromised the
informed and voluntary consent of the subjects, all of whom were
experienced subjects in ICR repellent tests.

	The applicable standards for this research are 40 CFR §26.1703,
prohibiting intentional exposure of pregnant or nursing women, or of
children under 18; 40 CFR §26.1705, requiring evidence of substantial
compliance with 40 CFR part 26, subparts A-L; 40 CFR §26.1303,
requiring documentation of ethical conduct; and FIFRA §12(a)(2)(P),
requiring fully informed, freely voluntary participation.  The
requirements of 40 CFR §26.1125 and §26.1601 for prior review of the
protocol by EPA and the HSRB were met.  The requirements of 40 CFR
§26.1303 and 40 CFR §26.1703 were met.

	The evidence that investigators initiated recruitment before final EIRB
approval of the consent form suggests that the conduct of the study may
not have been in substantial compliance with 40 CFR §26.1705 part 26,
subparts A-L.  The requirement of FIFRA §12(a)(2)(P) for fully
informed, fully voluntary consent of subjects may have been compromised
by initiation of recruitment before obtaining final IRB approval of the
ICF.

	EPA interprets 40 CFR §26.1111(a)(4) and (5) to mean that research is
not approved until both §26.1116 and §26.1117 have been satisfied;
however, EPA has learned that OHRP is considering guidance that would
allow recruiting to begin when the protocol and ICF have received at
least conditional IRB approval, as was true in this case.  The
initiation of this research before full IRB approval did not endanger
subjects, but led to procedural deviations from the protocol which may
or may not rise to the level of substantial non-compliance with 40 CFR
part 26, subparts A-L.

ICR A117 Charge Questions:

a.	Is this study sufficiently sound, from a scientific perspective, to
be used to assess the repellent efficacy of the formulations tested
against mosquitoes of the genus Culex?

b.   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?

	Clarifying Questions

	Dr. Philpott noted that the supporting information on ethical conduct
lists a third product to be tested (towelettes) and asked if this was a
mistake.  Mr. Carley responded that the protocol calls for testing of
two products and two products were tested.  Dr. Philpott inquired if EPA
has requested and received a telephone script for the recruiting
process.  Mr. Carley replied that there is a passage in the protocol
characterized as a “script” but it is vague and lacks detail.  EPA
does not know the exact context or content of the recruiting script.

	Dr. Menikoff questioned how the change from six pairs of two subjects
to two groups of six subjects affected the approval of the protocol.
Mr. Carley explained that the change was reasonable, given that it
simplified the testing and had no impact on results or ethics.  The
investigators should have submitted a protocol amendment to make this
change because it was possible to anticipate and was not made in
response to a hazardous testing situation.

	Dr. Menikoff requested a description of the IRB communication with the
principal investigator on February 18, 2008.  Mr. Carley explained that
on June 6, 2008, ICR included a copy of the June 3, 2008 email from IRB
to the principal investigator as supporting documentation that
recruiting could be initiated before receipt of the final approved ICF.
The letter does not specifically mention this situation, in which an
unconditional approval of the protocol and conditional approval of the
ICF had been received.  Dr. Menikoff noted that EIRB did not
specifically claim that the events violated its terms and said that it
appeared that the first telephone call to potential subjects may have
been to check availability and the protocol may not have been mentioned.
 The call might have been supplemental to what was described in the
protocol as the first recruitment call.  Mr. Carley commented that EPA
does not know the exact content of the call.  The protocol indicates
that an initial contact will be made to ask subjects if they are
interested and available for the study, and then subjects will be
informed about the study and the ICF will be described.  If subjects
agree to participate, the ICF will be sent to them and after receipt is
confirmed, ICR calls the subject and reviews the ICF within the next few
days.  There appears to be insufficient time for this process because of
when the approved ICF was sent.  A compression of the protocol (fewer
steps and fewer contacts with potential subjects) may have occurred.
Dr. Menikoff noted that the subjects other than the three who did not
receive the ICF were offered a chance to discuss the ICF.  The fact that
three people did not receive the ICF appears to be a violation.  Mr.
Carley stated that there were procedural violations, but the substantive
steps of the process were in place.

	Dr. Prentice commented that ICR began recruiting on February 18, 2008,
before final approval of the ICF and inquired about the nature of the
revisions to the ICF and whether they were substantive.  Mr. Carley
explained that there were approximately 15 changes to the ICF, and all
but two or three were minor editorial changes.  The exceptions were the
request by EIRB to insert standard language, including a paragraph that
informs subjects about resources on participation in studies.  These
resources include only links to the main portals to OHRP and the NIH,
and seem unlikely to be helpful concerning participation in this type of
study.  EPA believes that addition of this material is unnecessary and
will contact EIRB about this matter.  Dr. Prentice asked if there was
any documentation of the communication between the principal
investigator and EIRB that occurred on February 18, 2008.  Mr. Carley
responded that EPA had received only the June 6, 2008 clarification that
the ICR staff was “told” they could proceed with recruiting.  This
email from EIRB is dated June 3, 2008, and does not refer to the prior
communication.  Mr. Carley added that he had not had a chance to speak
with ICR about this issue in detail.

	Dr. Prentice remarked that the recruiting calls on February 18, 2008
could indicate use of an unapproved script, but the HSRB lacks the
information needed to decide if this is the case.  Mr. Carley agreed
that ICR’s characterization of their recruiting process was highly
inadequate.  Dr. Krishnan inquired if checking availability is
considered part of the recruiting process.  Mr. Carley replied that
this is part of the process.  Dr. Krishnan noted that ICR’s reply
states that potential subjects signed the ICFs, but does not say when
they signed them.  Mr. Carley explained that all subjects signed the ICF
on March 4, 2008, the day of testing.  There was insufficient time for
the subjects to sign the forms and mail them back to ICR.  A statement
in the supplemental materials states that all subjects signed the
approved ICF on the morning of March 4, 2008.  Dr. Krishnan noted that
in ICR’s response, they indicate that all subjects agreed to travel to
ICR to have their questions answered, and agreed to be prepared to sign
the ICF on the day of testing.  Mr. Carley clarified that all subjects
were invited to travel to ICR to discuss the ICF but none did.  All
subjects arrived on the morning of testing and discussed the ICF at that
time.  All the subjects participating in the protocol were experienced
subjects who had participated in previous ICR protocols.

	Dr. Parkin inquired when EIRB procedures had been previously submitted
to EPA.  Mr. Carley indicated that EIRB had submitted its procedures to
EPA approximately 1 year ago.  Dr. Parkin stated that because EPA had
received no documentation of EIRB procedures, the Board has no knowledge
concerning whether EIRB was following its procedures in review of this
protocol.

Public Comments

	Dr. Robin G. Todd of ICR, Mr. Niketas Spero of ICR, Dr. Ralph Piedmont
of Loyola College, and Mr. Andrew Pechko of Avon Products, Inc., on
behalf of ICR

	Mr. Niketas Spero (ICR) explained that on February 18, 2008, ICR
received a telephone call from EIRB, as is typical when they complete a
review.  EIRB explained that the protocol was approved and the ICF was
conditionally approved.  During the call, Ms. Karen Radcliffe (EIRB)
was asked if recruiting could begin.  She responded that recruiting
could begin, but the ICF could not be discussed.  Later that day, Mr.
Spero began the recruitment process but limited the substance of the
telephone calls to potential subjects to asking about interest and
availability.  March 4, 2008 was chosen as the test date to allow
sufficient time to raise the mosquitoes and recruit a sufficient number
of subjects.  Only subject availability was discussed on the call.  When
the approved ICF was received on February 26, 2008, Mr. Spero called the
available subjects back and discussed the ICF and protocol.  At this
time, subjects also were offered the opportunity to come to ICR and
discuss the ICF in further detail, but all declined this opportunity.

	Regarding the deviation of the protocol from six groups of two to two
groups of six, this was not considered until the planning meeting on the
day before testing.  ICR decided it would be easier to test 12 people if
there were two dedicated times for exposure in the cage.  There was
insufficient time to amend the protocol.  Mr. Spero acknowledged that
the investigators should have considered this approach earlier.

	Dr. Fisher inquired why the test date of March 4, 2008, had been
chosen.  Mr. Spero explained that this was based on the sponsor’s need
to present its report to EPA.  Also, raising mosquitoes needs to begin
approximately 2 weeks in advance, and ICR believed all paperwork would
be approved by this date.  Dr. Fisher asked when ICR had notified EIRB
of the change in the number of test groups.  Mr. Spero stated that this
was noted as a deviation and EIRB was contacted 10 days later.  Dr.
Fisher requested clarification regarding testing of the towelette
product.  Mr. Spero explained that ICR evaluated only the aerosol and
pump spray.  Testing will support the towelette product because the
three AIs are the same.  Although only two product types were tested,
the regulatory requirements for the towelette product also will be met.
Mr. Andrew Pechko (Avon Products, Inc.), on behalf of ICR, explained
that the DASH30 towelette uses the same liquid formulation that is in
the pump spray, so this efficacy test supports the towelette product.

	Dr. Fisher asked if ICR had provided its written recruitment script.
Mr. Spero explained that ICR did not use a script for this study, but
has one for future use that has been approved by EIRB.  EIRB approved
the vague script described in the protocol.  During the first call to
subjects (on February 18, 2008), subjects were informed that testing
would occur on March 4, 2008, and asked if they were interested and
available.  If they were, subjects were told that the ICF could not be
discussed because it had not yet been approved, but that once it was
approved, they would be contacted to discuss the form.

	Dr. Krishnan inquired if all subjects had seen the ICF only the day
before testing, or if they saw it on an earlier date.  Mr. Spero
explained that the ICF was approved on February 26, 2008.  Subjects
were called on that day and the ICF was discussed (in particular, the
exclusion criteria and parameters of the study), and it was mailed to
subjects the same day.  Subjects were called again on February 29, 2008,
after they had received the ICF.  This second call lasted approximately
5 to 10 minutes and indicated that all participants read the ICF and
were comfortable with ICR procedures.

	Dr. Philpott asked if subjects received compensation for traveling to
ICR to discuss the ICF, if they chose to do so.  Mr. Spero responded
that there was no compensation for this activity.  All subjects declined
to come in to discuss the ICF because they had participated in many
previous studies.  Dr. Philpott inquired about the subjects who did not
receive the ICF by mail and whether they had an opportunity to review
the ICF before testing began.  Mr. Spero explained that the ICF was read
over the phone (February 26, 2008) to those who did not receive it in
the mail.  The test day was scheduled to begin at 6:00 a.m., which
provided ample time for subjects to read the ICF and ask questions about
it before signing.

	Dr. Fisher asked if the boilerplate language that EIRB suggested
inserting included any language from the EPA Web site or just OHRP.  Mr.
Spero answered that it did not include EPA language.  Mr. Carley
clarified that there were three insertions of standard language, but no
major changes to the ICF.

Board Discussion

	Scientific Considerations – ICR A117

	Dr. Chambers opened the Board’s science discussion of ICR protocol
A117.  Use of a standard consumer dose of the repellent and counting
bites as opposed to landings was previously approved by the HSRB and
EPA.  She agreed with Mr. Carley that the change to two groups of six
participants did not affect the science of the protocol.  She concluded
that the results were scientifically valid.

	Dr. Krishnan agreed with EPA and Dr. Chambers that, given the purpose
of the study, the results are acceptable and sound.  He noted that there
was a typographical error in the table on page 4 referring to product
numbers.

	Dr. Young agreed that the results were scientifically valid, but she
commented further on issues related to mosquito studies in general.  She
expressed concern about conclusions drawn as a consequence of the study.
 The hypothesis is that the repellents will offer 8 hours of protection;
however, at 3 hours the product failed for one of the subjects; this
represents 8 percent of the subjects and is thus a significant finding.
She expressed concern about how this would affect the labels of the
products.

	Dr. Young noted the heavy reliance on the Rutledge and Gupta (1999)
meta-analysis paper for the sample design.  She stated that the
designers of this protocol over-relied on the analysis and that the
meta-analysis itself is flawed.  This analysis is reasonable to use for
rough power calculations, but in the documentation of the protocol there
is an assumption that if there are the same number of subjects in the
experiment, the same conclusions can be drawn as those described in
Rutledge and Gupta.  This is untrue.  In addition, many of the articles
used in the meta-analysis are flawed and the meta-analysis is weighted
toward large studies with small means; traditional modeling of means and
variance were not used.

	Dr. Young also noted problems related to right-censoring of the data.
Eleven subjects in this study had no bites at 10 hours, but one person
was bitten at 3 hours.  If these data are analyzed by Kaplan-Meier
analysis, the analysis falls apart when attempts are made to compute the
mean because more than 90 percent of the data points are censored.  This
is problematic for statistical analysis of the data.  To base the
conclusion of 8 hours ± 2 hours of protection on the Rutledge and Gupta
article is seriously flawed.  Careful consideration of how to analyze
these studies in the future is needed.  If the results claim to define a
mean, the mean is approximately 8 hours of protection; however, again
use of the Kaplan-Meier equation would be flawed.  Dr. Fisher asked Dr.
Young if she had any recommendations or suggestions for future studies.
Dr. Young suggested that there are different models that would be more
suitable for this work, but nothing is available in the published
literature comparable to the Rutledge and Gupta paper for discussion of
study power.  Re-analysis of the studies included in the Rutledge and
Gupta analysis also might be helpful.

	Dr. Fisher noted that this issue continues to arise in Board
discussions, but the Board has been unable to recommend useful
alternatives.  Dr. Carriquiry explained that the main problem is the
very small sample size.  To resolve this issue, either a larger sample
size or longer observation period (perhaps 15 hours to observe product
failure) is needed.  Dr. Young stated that failure should reach at least
50 percent before the study stops.  Dr. Fisher inquired if parametric
statistics were appropriate for this sort of study.  She added that
increasing the observation period to 15 hours was probably unreasonable.
 Dr. Young remarked that, on average, stating that the product offers 8
hours of protection is reasonable, but this will not include those for
whom the product fails early.

	Dr. Lebowitz agreed that there was no method for analyzing the data in
a way that would be statistically significant.  The policy issue in
question is what sort of information to include on the product label,
given the evidence.  He agreed with Dr. Young’s frustrations, but
noted that while these discussions have arisen before, changes in sample
size or length of observation period have not occurred.  He stated that,
regarding the answer to the scientific charge question, he agreed with
Drs. Chambers, Krishnan, and EPA, that the data are sound.  How EPA uses
the data to inform labeling is a regulatory issue for which the Board is
not skilled to provide advice.

	Dr. Fisher remarked that the charge states that, from a scientific
perspective, in conjunction with other available information, the study
established what it hypothesized.  She asked if the Board wanted to
include a statement that the data are sufficient for estimating a range
of response times, but not an average.  Labeling decisions are beyond
the purview of the Board.

	Dr. Young stated that it was not possible to obtain an unbiased
estimate of the mean or derive the standard deviation using these data.
Dr. Brimijoin stated that he agreed with the consensus that the study
has adequate scientific validity and answers the charge question.  He
agreed with Dr. Lebowitz that the science was as good as or better than
that in the typical insect repellent study.  The Board can offer any
suggestions it chooses to EPA to guide them on regulatory decisions, but
these are outside the purview of the Board.  He expressed sympathy with
the frustrated statisticians regarding the study design, power, and
interpretation.  The raw data from these studies are available and the
Board can revisit them to try to determine a more appropriate analytical
approach.  Dr. Brimijoin stated that these data are consistent with
current “best practices” for insect repellent studies.  Two changes
are needed to improve the studies.  Insect repellent investigators must
rethink their study designs in light of the proposed statistical
analyses.  The statistical community also should consider which
measurements and endpoints would be appropriate for these studies.  He
commented on survival analyses for treatments for fatal conditions in
which the endpoint is 100 percent death; however, such studies do not
need to achieve a 100 percent death rate for detection of the effects of
treatment to be possible.  Unlike most cancer chemotherapeutics, insect
repellents work well, approaching a 100-percent success rate over times
that are reasonable for testing.  It would not be practical to test
repellents in a research setting for much longer than 8 to 10 hours.  He
disagreed with Dr. Young’s assessment that because all data are
censored except for one data point that the calculated mean is
meaningless.  He noted that if 99 out of 100 subjects were protected for
more than 10 hours but one was protected for only 2 hours, the
protection range would not be 2 to 200 hours; nearly everyone in this
example received complete protection.  Dr. Brimijoin stated that he was
not prepared to offer EPA advice on regulatory issues or ways to treat
the data, but the data presented at this meeting are meaningful for
protection; a mix of common sense and mathematics should be applied to
assessment of the data.

	Dr. Carriquiry countered that, given the data from this study, she
would expect there to be 8 to 10 failures in a study of 100 subjects.
If investigators wish to observe a rare event, they must increase their
sample size.  She stated that she would not oppose the Board’s
conclusion that the study is acceptable, but it was problematic that the
data did not allow estimation of an unbiased mean.  Dr. Brimijoin
commented that instead of increasing sample size, another option would
be to increase mosquito pressure to perhaps 10 times that used in these
experiments; another alternative would be to decrease the amount of
repellent used.  Dr. Young remarked that it would be possible to
estimate the proportion of users who would receive less than 8 hours of
protection if the sample size was larger; current data would estimate a
failure rate of 8 percent.  Dr. Fisher noted that the typical sample
size of 10 was acceptable in part to minimize risk; however, laboratory
experiments do not carry the same degree of risk as field studies.

	Dr. Lebowitz interjected that the Board was making assumptions about
what might or might not happen, given changes to the protocol.  The
Board can only carefully consider and discuss the information it is
given.  The Board also does not have any adequate recommendations for
changes for future designs.  He recommended that EPA consider the issues
raised at this meeting and request that the HSRB discuss them further,
if the Agency desires.  Dr. Chambers stated that EPA needs some
consistent guidelines to help the Board focus on scientific issues,
rather than study design and regulatory matters.  Dr. Fisher stated that
in her opinion, the data were useful for assessing efficacy, but not for
determining a mean or standard deviation; however, the study was
well-executed and questions about limiting the uses of the data have
arisen in the past.

	Dr. Ralph Piedmont (Loyola College), on behalf of ICR, stated that he
agreed that the Rutledge and Gupta study is inadequate and flawed, but
it represents the current state of knowledge regarding repellent
studies.  In designing the study, the goal was to be conservative; the
Rutledge and Gupta study was the only report available for guidance on
power.  With a sample size of 12, it is possible to have a mean estimate
of protection of up to 10 hours ± 2 hours.  Given the current state of
the science, these data indicate that the product works for 8 hours ±
2 hours.  He agreed that use of the actual mean is not supported because
it is biased and 95 percent confidence intervals cannot be justified;
however, the use of 12 subjects was scientifically justified given the
existing knowledge.  Dr. Lebowitz agreed that the Rutledge and Gupta
paper was insufficient, with the Board’s assessment of the statistics
of the study, and with the conclusion that the Board does not believe
the evidence is sufficient to agree with conclusions about means and
standard deviations drawn using the results of the study.

	Dr. Fisher summarized that the Board consensus was that the study was
conducted using best practices following an approved protocol; however,
the Board does not believe that the data can be used to develop a mean
and standard deviation.  EPA will decide if this is possible and how
they will use the data.  She also agreed that the investigators had used
current best practices to design their study.

	Ethical Considerations – ICR A117

	Before the discussion began, Dr. Fisher reminded the Board of its
consensus regarding protocol deviations:

Any study executed prior to IRB approval of the ICF and the protocol, or
changed in ways that were not approved by the IRB will be judged by the
Board as failing to meet the applicable requirements of §40 CFR part
26, subpart K.

If EPA submits to the Board for review a completed protocol with
scientific deviations from the original protocol reviewed by the Board,
the EPA review of the completed protocol should provide the Board with
EPA's opinion regarding why the deviation did not meet the requirement
for re-review and why the protocol still meets the applicable
regulations.

	Dr. Philpott opened the ethics discussion of ICR protocol A117 by
stating that the study had been adequately designed to minimize risks.
The relevant risks included participating in research conducted under
hot and humid conditions, adverse events associated with use of the
products, exposure to insect bites, and exposure to vector-born
illnesses.  The risks associated with the hot and humid research
environment are minimized by limiting participants to 5-minute intervals
in this environment.  The risks associated with use of the product are
minimized because the AI (picaridin) is registered and widely used,
there are adequate stopping rules, and people with skin reactions to the
products are excluded from the research.  Bites are expected, but risks
from exposure to bites are minimized by excluding participants with a
history of severe reactions to insect bites and by close monitoring and
providing medical care.  The risk of vector-borne disease is minimized
because the research uses laboratory-raised mosquitoes that have not had
a previous blood meal.  The study investigators also contacted
participants after the research was complete to ask about any adverse
events.

	Key issues of concern related to this protocol include the protocol
deviation and consent issues.  Protocol deviations that appear planned,
but are not reviewed by an IRB arise frequently.  In this case, the
change from testing six pairs of two subjects to testing two groups of
six subjects was a planned violation because the investigators discussed
this change the day before testing began.  It was possible for the
investigators to call EIRB and obtain some sort of approval for the
change, but they did not do so.  The Board has explicitly explained that
federal regulations state that the only allowable protocol violations
are those that occur to protect the subjects.  In addition, ICR did not
contact EIRB about this violation until 10 days after the research took
place, and did not include EIRB’s response in the documentation of the
research.

	Recruitment took place prior to revisions and final approval of the
ICF, although the Board has been told that ICR received verbal approval;
however, on page 92 of the report there is a written statement from the
Chair of the IRB stating that a study may not commence any further
research activity, including scheduling, until a stamped ICF is
received.  This statement is dated August 2007.  ICR has clearly
violated IRB rules regarding recruitment.  Because of this,
Dr. Philpott stated that it was his opinion that the protocol is not in
compliance with 40 CFR part 26 and he recommended that EPA cannot use
the results of this study.

	Dr. Menikoff stated that he disagreed, to some extent, with Dr.
Philpott’s conclusions.  He noted that he had objected to the
Board’s consensus on protocol violations previously, and believed
other Board members did as well, because the statement does not include
a consideration of intent.  A discussion of intent occurred, but
statements related to intent were eliminated from the consensus.  The
Board is asked to consider if a protocol is in “substantial”
compliance; the Board consensus statement appears to demand
“perfect” compliance.  Given Mr. Carley’s thorough review, the
Board may not be able to approve any research if it demands perfect
compliance.  Dr. Fish added that this particular study was conducted
before the Board created its statement and thus the consensus statement
should not be applied as rigorously.  Dr. Menikoff stated that in terms
of consent and recruitment, differences in facts exist.  The written IRB
materials differ from statements that the IRB emailed or said to the
investigators.  This matter can be investigated.  If EIRB informed the
investigators by telephone call that recruitment could begin despite the
lack of a finalized ICF, then the study is not in substantial
noncompliance.  Calling people who previously agreed to be contacted
about participation in these studies to ask if they are available on a
certain date should be acceptable.  Dr. Menikoff added that reading the
ICF over the telephone to those who did not receive the ICF in the mail
also is not necessarily a violation.

	Regarding the change in protocol design, this also may not rise to the
level of substantial noncompliance, given that it did not increase
subject risk; however, because the deviation was planned, Dr. Menikoff
stated he was more likely to agree with Dr. Philpott on this matter.

	Dr. Fisher agreed that if EIRB gave permission to begin scheduling
activities, the sponsor is in compliance.  The HSRB has questioned IRB
activities in the past; if this IRB did not behave in a legitimate
manner, the HSRB should make a strong statement to this effect.  Dr.
Menikoff agreed, but added that this may be complicated by apparent
changes in recruitment policies taking place through OHRP and the IRBs.

	Dr. Chadwick stated that the Board is continually disappointed by
investigators who do not follow their own protocols; however, it may be
unreasonable to expect 100-percent compliance.  Many investigators view
protocols as guidelines, while regulatory entities and the HSRB appear
to view them more as “written in stone.”  The Board needs to
recognize that two types of changes to protocols occur:  deviations,
which affect neither science nor risk, and violations, which affect
subject protection, or science, or both.  In this case, a deviation
occurred.  It is true that the investigators did not follow the written
protocol, but this did not result in subject harm or damages to
scientific validity, which the Board is charged with reviewing.  The
Board must carefully consider wording; the HSRB believes that
recruitment means enrollment, but a member of an IRB may believe that
recruitment includes asking about availability.  Dr. Chadwick cautioned
sponsors that other agencies have the policy of “if it is not written,
it did not happen.”  Documentation is important for regulatory
agencies, and justifying an action on verbal advice is a bad choice.
Dr. Chadwick concluded that in his opinion, ICR protocol A117 is
ethically acceptable.

	Dr. Fish agreed with Dr. Chadwick.  Ethicists may consider recruitment
to be part of the informed consent process because most recruitment
processes provide information about the study to the potential subjects,
and it is important that this information is approved by an IRB.  In
this case, however, recruitment involved knowledgeable subjects and
information on this study was not provided to them, except to tell them
that the study would take place on March 4, 2008.  If this is the only
information provided and no specifics of the study were discussed before
approval of the ICF was obtained from EIRB, recruitment is in compliance
with the intent of the regulations.

	Dr. Prentice agreed with Drs. Chadwick, Fish, and Menikoff.  He noted
that the risk-benefit balance is highly important to the IRB’s
approval of a study.  In this case, the primary risk is exposure to
mosquito bites and the discomfort associated with such bites.  There is
no direct benefit to the subject, only to society for registration of an
alternative efficacious repellent against mosquitoes that harbor WNV.
If the Board declines to accept the data, the risk-benefit balance has
been negated for every subject, which is a serious matter.  Dr. Prentice
agreed that any unethical or significant deviations should not be
ignored, but in this case, the deviations are minor.  The deviations
indicate that the system is working; a deviation occurs, is reported,
and a mitigation plan is put in place.  He disagreed with Dr.
Philpott’s opinion that the results should not be used by EPA.

	Dr. Philpott agreed with the points raised by his fellow Board members,
but expressed concern that, based on the written materials reviewed by
the Board, the protocol is not in compliance with ethics regulations.
He was concerned that the Board might be setting a precedent by making
value judgments.  In light of the Board consensus on protocol
deviations, Dr. Philpott concluded that he could not recommend EPA use
of the data.

	Dr. Lebowitz noted that for the National Incident Management System,
written or oral commands are acceptable, except in unusual cases where
the regulations require a written command.  He agreed with Dr. Chadwick
regarding the difference between deviations and violations.  If the
Board can conclude that neither the scientific nor ethical standards
were violated, deviations should be accepted as “human error.”  The
Board should not be so rigid that it cannot operate within this system.

	Dr. Prentice noted that slide 32 of EPA’s review stated “led to
procedural deviations from the protocol which may be deemed to rise to
the level of substantial non-compliance with subparts A through L of 40
CFR part 26,” but the charge asks if the “available information
supports a determination that this study was conducted in substantial
compliance with subparts K and L of EPA regulations at 40 CFR part
26.”  “Substantial compliance” indicates that a level of
compliance less than 100 percent would be acceptable.  This protocol was
conducted in sufficient compliance that the Board does not have concerns
about the science or blatant violations of the regulations.  Dr.
Prentice stated that the language in the charge question is limiting and
should be revisited by EPA.

	Mr. Jordan explained that the charge question language mirrors the
standard language in EPA’s regulations.  EPA may rely on a completed
study if there is evidence to indicate it substantially comports with
the regulations in subpart L.  EPA does not require 100-percent
compliance; the drafters of the regulations (Mr. Carley and Mr. Jordan)
wanted to include the notion of acceptability.  EPA recognizes that
demanding 100-percent compliance would mean that a single deviation
would result in rejection of all protocols and would result in large
numbers of repeated studies; EPA does not intend for such a situation to
arise.  The regulations ask the Board to make value judgments.
Concerning the Board consensus on protocol deviations, Mr. Jordan
agreed with the first point that an investigator who does not follow the
approved protocol fails to meet subpart K of the regulations.  But
subpart Q, which asks if the study is acceptable for EPA, indicates that
“substantial compliance” will suffice.  The deviations EPA notes are
deviations that investigators should not make knowingly, but EPA
recognizes that such deviations do happen and when they do, they should
be reported and corrected.  Mr. Jordan stated the HSRB’s statement was
acceptable if it does not affect the “substantial compliance”
standard of subpart Q.

	Dr. Philpott commented that according to the EIRB written statement,
recruitment could not be started until the approved ICF was received.
Mr. Jordan explained that the August 2, 2007 approval was part of the
IRB review cycle preceding Board review in October 2007.  Before the
information came to the Board, a final protocol with approval of the IRB
was received.  The protocol was then revised and the telephone calls
between the sponsor and EIRB occurred in a different cycle of IRB
review.  Dr. Philpott noted that the language in the letter was
“boilerplate” and that the HSRB has not had access to IRB procedural
language because it is Confidential Business Information.  The Board
cannot assume that EIRB changed its language in the absence of written
information that indicates that beginning the recruitment process before
receipt of the approved ICF was acceptable.  Dr. Philpott stated that he
was reluctant to approve this study, and strongly recommended that no
study should be commenced in any way without final approval and a
stamped ICF.

	Dr. Fisher interjected that the Board must consider two issues that
relate to recruitment and relate to the change in study design.  She
agreed that the changes did not result in increased risk to
participants; the Board should consider whether this constitutes
“substantial” noncompliance.  The Board must take at face value the
claim from the sponsor (and the email dated June 3, 2008) that ICR was
allowed to begin recruitment before receipt of the finalized ICF.  The
Board may disagree with EIRB’s decision, but given that the decision
may be based on new directives from OHRP, this decision may not be a
violation of EIRB procedures.

	Dr. Philpott acknowledged that his was the minority opinion.  He would
accept the consensus to approve the study, but wanted to include a
strong statement that written confirmation of changes is needed and
verbal information is unacceptable.  Dr. Menikoff agreed that EPA should
verify changes in EIRB policies.  Dr. Fisher noted that sponsors should
not accept IRB procedures that may place them in jeopardy of having a
study disapproved.

	Dr. Fisher remarked that the change in the study design was a deviation
that did not increase risk to subjects, but the fact that ICR waited 10
days to report this deviation to EIRB is troubling.  The sponsors should
have immediately emailed EIRB about this change.  The study was in
substantial compliance, but in the future the Board may judge more
harshly these non-documented changes.  Dr. Philpott added that the Board
must explicitly state that it will not accept hearsay as evidence, but
instead will require clear written documentation of changes and
permissions; the investigators and EPA must ensure that such information
is made available to the Board.  Dr. Chadwick countered that a rule
saying in effect, “If it is not written, it does not exist,” would
be too stringent.  Dr. Brimijoin agreed.

	Dr. Fisher stated that the majority of the Board agreed that the
protocol was in substantial compliance with the relevant regulations.
The Board also should detail the non-substantial, but important
deviations that occurred.  Drs. Chadwick, Fish, Menikoff, and Philpott
will draft this statement.

	Dr. Fisher recommended changing the Board’s consensus statement on
protocol deviations.  The Board always has the option of recommending
rejection or acceptance of a protocol.  The language of this statement
needs to be clarified, especially with respect to the issue of
“substantial” compliance.  Dr. Chadwick agreed with Mr. Jordan that
the deviations in this protocol represented violations of the
regulation, but it is more difficult to decide if the protocol is in
substantial non-compliance.  The Board’s statement should incorporate
subpart Q; compliance, or lack thereof, with subpart K may be clear, but
the Board will need to consider more thoroughly if a protocol is not in
compliance with subpart Q.  Dr. Menikoff stated that he did not object
to such changes, but was not convinced it would greatly influence Board
review of protocols.  The Board is rarely asked to judge if a protocol
is in 100-percent compliance.  Dr. Fisher stated that the Board’s
report for this meeting would include amendment of the Board’s
statement on protocol deviations, incorporating consideration of
compliance with subpart Q.

Concluding Remarks

	Mr. Jordan provided a preview of the October 2008 HSRB Meeting agenda.
The Board will review at least three completed insect repellent studies
conducted in accord with previously reviewed protocols.  EPA also is
analyzing literature on potassium triiodide, involving intentional
dosing in human subjects to evaluate toxicities.  EPA may wish to use
this information for risk assessment activities, and if so, the Board
will review these studies.  The Board also will review additional
protocols from the AEATF and AHETF.  AEATF will present a scenario to
measure exposure from aerosol products.  AHETF is currently choosing
protocols to present for review.

	Dr. Fisher asked if there is existing pre-rule data that the Board must
review in advance of evaluation of open-cab scenarios planned by AHETF.
Mr. Jordan explained that because these studies were initiated before
the rule was in place and did not report a toxic endpoint, Board review
is not needed.  However, EPA will work to provide the Board with data
and conclusions of this data in a summary form.

	Dr. Lewis thanked Board members for their efforts and his EPA
colleagues for their preparation and presentations given at this
meeting.  He stated that the next HSRB meeting will take place October
21-24, 2008, and will be announced in the Federal Register.  The Board
will release its April 2008 meeting report, prepare its report for this
meeting and send drafts to Drs. Fisher and Lewis within the next 2
weeks.  Dr. Lewis adjourned the meeting.

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 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 		List of HSRB Members

Attachment B 		Federal Register Notice Announcing Meeting

Attachment C 		Meeting Agenda

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., DABT

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

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., FCCP

Retired Professor of Public Health (Epidemiology) and Medicine

Research Professor 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.

Director, Office of Human Subjects Research

Office of the Director

National Institutes of Health

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

Science 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

University of Nebraska Medical Center

Omaha, NE

Richard R. Sharp, Ph.D. *

Director of Bioethics Research

Department of Bioethics

Cleveland Clinic

Cleveland, OH

Linda J. Young, Ph.D.

Professor of Statistics

Department of Statistics

Institute of Food and Agricultural Sciences

University of Florida

Gainesville, FL

* Not in attendance

** Attended via telephone

Attachment B

Federal Register Notice Announcing Meeting

Human Studies Review Board; Notice of Public Meeting

[Federal Register: May 30, 2008 (Volume 73, Number 105)]

[Notices]

[Page 31117-31118]

[DOCID:fr30my08-49]

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

ENVIRONMENTAL PROTECTION AGENCY

[EPA–HQ–ORD–2008–0035; FRL–8573–9]

Human Studies Review Board; Notice of Public Meeting

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

SUMMARY: The U.S. Environmental Protection Agency's (EPA or Agency)
Office of the Science Advisor (OSA) announces a public meeting of the
Human Studies Review Board (HSRB) to advise the Agency on EPA's
scientific and ethical review of human subjects research.

    Dates: The public meeting will be held from June 24-June 25, 2008
from 8:30 a.m. to approximately 5:30 p.m., Eastern Time (However, the
second day may not be needed).

    Location: Environmental Protection Agency, Conference Center—Lobby
Level, One Potomac Yard (South Bldg.), 2777 S. Crystal Drive, Arlington,
VA 22202.

    Meeting Access: Seating at the meeting will be on a first-come
basis. To request accommodation of a disability please contact the
person listed under FOR FURTHER INFORMATION CONTACT at least 10 business
days prior to the meeting, to allow EPA as much time as possible to
process your request.

    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.

ADDRESSES: Submit your written comments, identified by Docket ID No.
EPA-HQ-ORD-2008-0355, by any of the following methods:

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

    E-mail<EMAIL_ADDRESS>
    USPS Mail: Environmental Protection Agency, EPA Docket Center
(EPA/DC), ORD Docket, Mailcode: 28221T, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460.

    Hand or Courier 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 Ave., NW., Washington DC. The
hours of operation are 8:30 a.m. to 4:30 p.m. Eastern Standard Time
(EST), Monday through Friday, excluding Federal holidays. Please call
(202) 566-1744 or e-mail the ORD Docket at<EMAIL_ADDRESS>for
instructions. Updates to Public Reading Room access are available on the
Web site (http://www.epa.gov/epahome/dockets.htm).

    Instructions: Direct your comments to Docket ID No.
EPA-HQ-ORD-2008-0355. EPA's policy is that all comments received will be
included in the public docket without change and may be made available
online at 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 through
http://www.regulations.gov or e-mail that you consider to be CBI or
otherwise protected from disclosure. The 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 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.

FOR FURTHER INFORMATION CONTACT: Any member of the public who wishes
further information should contact Lu-Ann Kleibacker, EPA, Office of the
Science Advisor, (8105R), Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (202)
564-7189; fax:<PHONE_NUMBER>; e-mail address:
<EMAIL_ADDRESS>General information concerning the EPA HSRB
can be found on the EPA Web site at http://www.epa.gov/osa/hsrb/.

SUPPLEMENTARY INFORMATION:

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 particular interest to persons who conduct or assess
human studies, especially studies on substances regulated by EPA and to
persons who may sponsor or conduct research with human subjects with the
intention to submit it to EPA for consideration under the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) or section 408 under
the Federal Food, Drug, and Cosmetic Act (FFDCA). 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?

    You may access this Federal Register document electronically either
through http://www.regulations.gov or through the EPA Web site under the
Federal Register listings at http://www.epa.gov/fedrgstr/.

    Docket: All documents in the docket are listed in the
http://www.regulations.gov index under the docket number. Even though it
will be listed by title in the index, some information is not publicly
available, e.g., CBI or other information whose disclosure is restricted
by statute. Copyright material will be publicly available only in hard
copy. Publicly available docket materials are available either
electronically in 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. EST, Monday through
Friday, excluding Federal holidays. Please call<PHONE_NUMBER> or e-mail
the ORD Docket at<EMAIL_ADDRESS>for instructions. Updates to Public
Reading Room access are available on the Web site
(http://www.epa.gov/epahome/dockets.htm). EPA's position paper(s),
charge/questions to the HSRB, and the meeting agenda are anticipated to
be available by late May 2008, if not earlier. In addition, the Agency
may provide additional background documents as the materials become
available. You may obtain electronic copies of these documents, and
certain other related documents that might be available electronically,
from the regulations.gov Web site and the HSRB Web site at
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.

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

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

    a. Explain your views as clearly as possible.

    b. Describe any assumptions that you used.

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

    d. Provide specific examples to illustrate your concerns and suggest
alternatives.

    e. 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-2008-0355 in the subject line on
the first page of your request.

    a. Oral comments. Requests to present oral comments will be accepted
up to June 17, 2008. 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, June 17, 2008 in order to be included on the meeting
agenda and to provide sufficient time for the HSRB Chair and HSRB
Designated Federal Officer (DFO) to review the agenda to provide an
appropriate public comment period. The request should identify the name
of the individual making the presentation, the organization (if any) the
individual will represent, and any requirements for audiovisual
equipment (e.g., overhead projector, LCD projector, chalkboard). Oral
comments before the HSRB are limited to five minutes per individual or
organization. Please note that this limit applies to the cumulative time
used by 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 multiple individuals sign up separately to speak on their behalf.
Each speaker should bring 25 copies of his or her comments and
presentation slides for distribution to the HSRB at the meeting. At the
discretion of the Board Chair and DFO, public commenters, if present
during the Board's discussion, may be asked to provide clarification of
their comments to assist the Board in their discussion.

    b. 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 five business days prior to the beginning of the
meeting. 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, June 17, 2008. You should submit your comments using
the instructions in Unit I.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

1. Human Studies Review Board

    The HSRB is a Federal advisory committee operating in accordance
with the Federal Advisory Committee Act (FACA) 5 U.S.C. App.2 Sec.  9.
The HSRB provides advice, information, and recommendations to EPA on
issues related to scientific and ethical aspects of human subjects
research. The major objectives of the HSRB are to provide advice and
recommendations on: (a) Research proposals and protocols; (b) reports of
completed research with human subjects; and (c) how to strengthen EPA's
programs for protection of human subjects of research. The HSRB reports
to the EPA Administrator through EPA's Science Advisor.

2. Topics for Discussion

    For this meeting of the HSRB, the Board will present for HSRB review
scientific and ethical issues surrounding:

The Governing Document, the compilation of Standard Operating
Procedures, the scenario design document, and two associated protocols
from the Agricultural Handlers Exposure Task Force (AHETF), which
collectively describe research to monitor exposure of subjects who apply
an agricultural pesticide using airblast equipment in closed cabs.

A report from a completed laboratory study to evaluate the efficacy in
repelling mosquitoes of the genus Culex of two registered products
containing picaridin.

    The Board may also be reviewing its draft April 9-10, 2008 meeting
report for subsequent Board approval. In addition, the HSRB may also
discuss planning for future HSRB meetings.

3. Meeting Minutes and Reports

    Minutes of the meeting, summarizing the matters discussed and
recommendations, if any, made by the advisory committee regarding such
matters will be released within 90 calendar days of the meeting. Such

minutes will be available at http://www.epa.gov/osa/hsrb/ and
http://www.regulations.gov. In addition, information concerning a Board
meeting report, if applicable, can be found at http://www.epa.gov/osa/

hsrb/ or from the person listed under FOR FURTHER INFORMATION CONTACT.

Dated: May 23, 2008.

George Gray,

EPA Science Advisor.

[FR Doc. E8-12144 Filed 5-29-08; 8:45 am]

BILLING CODE 6560-50-P

Attachment C

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

HUMAN STUDIES REVIEW BOARD (HSRB)

JUNE 24-25, 2008 *

PUBLIC MEETING

Tuesday, June 24, 2008

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:<PHONE_NUMBER>

Docket Number: EPA-HQ-ORD-2008-0355

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

8:40 AM	Welcome – Elizabeth Lee Hofmann, Ph.D. (Deputy Director,
Office of the Science Advisor [OSA])

8:50 AM	Opening Remarks – Debbie Edwards, Ph.D. (Director, Office of
Pesticide Programs [OPP], EPA)

9:00 AM	Meeting Administrative Procedures – Paul Lewis, Ph.D.
(Designated Federal Officer [DFO], HSRB, OSA, EPA)

9:10 AM	EPA Follow-up on Pesticide Specific HSRB Recommendations – Mr.
William Jordan (OPP, EPA)

AHETF Pesticide Handler Protocols: Closed-Cab Airblast Scenario

9:30 AM	Overview – Mr. William Jordan (OPP, EPA)

9:45 AM	Science and Ethics Assessment of AHETF Protocol – Mr. Jeffrey
Evans (OPP, EPA), Mr. Matthew Crowley (OPP, EPA) and Mr. John Carley
(OPP, EPA)

10:30 AM	Break

10:45 AM	Science and Ethics Assessment of AHETF Protocol (continued) –
Mr. Jeffrey Evans (OPP, EPA), Mr. Matthew Crowley (OPP, EPA) and Mr.
John Carley (OPP, EPA)

11:30 AM	Public Comments

12:00 PM	Lunch

1:00 PM	Board Discussion

If AHETF’s proposed closed-cab airblast application scenario design,
field study protocols AHE55 and AHE56, and supporting documentation are
revised as suggested in EPA’s reviews:

Does the research appear 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?

Does the research appear to meet the applicable requirements of 40 CFR
part 26, subparts K and L?

3:30 PM	Break

Completed ICR Mosquito Repellent Efficacy Study A117

3:45 AM	EPA Science and Ethics Assessment of Completed ICR Mosquito
Repellent Efficacy Study A117 – Mr. Mark Suarez (OPP, EPA) and Mr.
John Carley (OPP, EPA)

4:45 PM	Public Comments

5:15 PM	Adjournment – Celia Fisher, Ph.D. (HSRB Chair) and Paul Lewis,
Ph.D. (HSRB DFO)

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

HUMAN STUDIES REVIEW BOARD (HSRB)

JUNE 24-25, 2008 *

PUBLIC MEETING

Wednesday, June 25, 2008

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)

Completed ICR Mosquito Repellent Efficacy Study A117

8:45 AM	Board Discussion

Is this study sufficiently sound, from a scientific perspective, to be
used, in conjunction with other information, to assess the repellent
efficacy of the formulations tested against mosquitoes of the genus
Culex?

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?

Review of April 9-10, 2008 HSRB Meeting Report

9:45 AM	Review Process – Celia Fisher, Ph.D. (HSRB Chair)

9:55 AM	Public Comments

10:15 AM	Break

10:30 AM	Board Discussion and Decision on Report – Celia Fisher, Ph.D.
(HSRB Chair)

12:30 PM	Concluding Remarks – Mr. William Jordan (OPP, EPA)

12:35 PM	Adjournment – Celia Fisher, Ph.D. (HSRB Chair) and Paul
Lewis, Ph.D. (HSRB DFO)

* 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:<PHONE_NUMBER> or
email<EMAIL_ADDRESS>
  PAGE  1  of   NUMPAGES  69


[Federal Register Volume 79, Number 172 (Friday, September 5, 2014)]
[Notices]
[Pages 53049-53050]
[FR Doc No: 2014-21167]

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

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Project No. 2911-038]

Southeast Alaska Power Agency; Notice of Application Accepted for
Filing, Ready for Environmental Analysis, Soliciting Comments, Motions
To Intervene, Protests, Recommendations, Terms and Conditions, and
Fishway Prescriptions

    Take notice that the following hydroelectric application has been
filed with the Commission and is available for public inspection:
    a. Type of Application: Amendment of License.
    b. Project No.: 2911-038.
    c. Date Filed: July 21, 2014.
    d. Applicant: Southeast Alaska Power Agency.
    e. Name of Project: Swan Lake Hydroelectric Project.
    f. Location: The project is located on Falls Creek on Revillagigedo
Island, Alaska in Ketchikan Gateway Borough. The project occupies
federal lands managed by the U.S. Forest Service within the Tongass
National Forest.
    g. Filed Pursuant to: Federal Power Act, 16 U.S.C. 791a-825r.
    h. Applicant Contact: Trey Acteson, CEO, Southeast Alaska Power
Agency, 1900 First Avenue, Suite 318, Ketchikan, AK 99901, (907) 228-
2281.
    i. FERC Contact: Mr. Steven Sachs<PHONE_NUMBER> or
<EMAIL_ADDRESS>    j. Deadline for filing motions to intervene and protests, comments,
recommendations, terms and conditions, and fishway prescriptions is 60
days from the issuance date of this notice by the Commission; reply
comments are due 105 days from the issuance date of this notice by the
Commission. The Commission strongly encourages electronic filing.
Please file any motion to intervene, protest, comments, and/or
recommendations using the Commission's eFiling system at http://www.ferc.gov/docs-filing/efiling.asp. Commenters can submit brief
comments up to 6,000 characters, without prior registration, using the
eComment system at http://www.ferc.gov/docs-filing/ecomment.asp. You
must include your name and contact information at the end of your
comments. For assistance, please contact FERC Online Support at
<EMAIL_ADDRESS>(866) 208-3676 (toll free), or (202) 502-
8659 (TTY). In lieu of electronic filing, please send a paper copy to:
Secretary, Federal Energy Regulatory Commission, 888 First Street NE.,
Washington, DC 20426. The first page of any filing should include
docket number P-2911-038.
    k. Description of Request: The applicant proposes to install a 20-
foot-wide vertical gate and a 78-foot-wide flashboard system on the
spillway to raise the maximum elevation of the impoundment by 15 feet.
The proposal would inundate an additional 94 acres of land,
approximately 26 of which are managed by the U.S. Forest Service. The
applicant also proposes to raise the non-overflow section of the dam by
about 1.5 feet and raise the intake gate tower by 15 feet. The proposal
would not change the project boundary or the authorized installed
capacity of the project.
    l. Locations of the Application: A copy of the application is
available for inspection and reproduction at the Commission's Public
Reference Room, located at 888 First Street NE., Room 2A, Washington,
DC 20426, or by calling<PHONE_NUMBER>. This filing may also be viewed
on the Commission's Web site at http://www.ferc.gov/docs-filing/efiling.asp. Enter the docket number excluding the last three digits in
the docket number field to access the document. You may also register
online at http://www.ferc.gov/docs-filing/esubscription.asp to be
notified via email of new filings and issuances related to this or
other pending projects. For assistance, call 1-866-208-3676 or email
<EMAIL_ADDRESS>for TTY, call<PHONE_NUMBER>. A copy is
also available for inspection and reproduction at the address in item
(h) above.
    m. Individuals desiring to be included on the Commission's mailing
list should so indicate by writing to the Secretary of the Commission.
    n. Comments, Protests, or Motions to Intervene: Anyone may submit
comments, a protest, or a motion to intervene in accordance with the
requirements of Rules of Practice and Procedure, 18 CFR 385.210, .211,
.214. In determining the appropriate action to take, the Commission
will consider all protests or other comments filed, but only those who
file a motion to intervene in accordance with the Commission's Rules
may become a party to the proceeding. Any comments, protests, or
motions to intervene must be received on or before the specified
comment date for the particular application.
    o. Filing and Service of Responsive Documents: All filings must (1)
bear in all capital letters the title ``COMMENTS'', ``PROTEST'',
``MOTION TO INTERVENE'', ``TERMS AND CONDITIONS'' or ``FISHWAY
PRESCRIPTIONS'' as applicable; (2) set forth in the heading the name of
the applicant and the project number of the application to which the
filing responds; (3) furnish the name, address, and telephone number of
the person protesting or intervening; and (4) otherwise comply with the
requirements of 18 CFR 385.2001 through 385.2005. All comments, motions
to intervene, or protests must set forth their evidentiary basis and
otherwise comply with the requirements of 18 CFR 4.34(b). All comments,
motions to intervene, or protests should relate to project works which
are the subject of the amendment. Agencies may obtain copies of the
application directly from the applicant. A copy of any protest or
motion to intervene must be served upon each representative of the
applicant specified in the particular application. If an intervener
files comments or documents with the Commission relating to the merits
of an issue that may affect the

responsibilities of a particular resource agency, they must also serve
a copy of the document on that resource agency. A copy of all other
filings in reference to this application must be accompanied by proof
of service on all persons listed in the service list prepared by the
Commission in this proceeding, in accordance with 18 CFR 4.34(b) and
385.2010.

    Dated: August 26, 2014.
Kimberly D. Bose,
Secretary.
[FR Doc. 2014-21167 Filed 9-4-14; 8:45 am]
BILLING CODE 6717-01-P