Center for Scientific Review Advisory Committee Meeting

National Institutes of Health

May 20, 2002

The Center for Scientific Review (CSR) convened the 29th meeting of its
Advisory Committee at 9:00 a.m. on Monday, May 20, 2002, in Conference
Room 9100, Rockledge II Building. The entire meeting was convened in
open session. Dr. Karen Matthews presided as Chair.

## Members

Karen Matthews, Ph.D., Chair Susan Berget, Ph.D.

Michael Colvin, M.D. James Kushner, M.D.

Edward Pugh, Jr., Ph.D.

## Ad Hoc Advisor

Michael Leon, Ph.D.

Dr. Brent Stanfield, CSR Deputy Director, was the Executive Secretary
for the meeting.

**Welcome and Opening Remarks**

Dr. Matthews welcomed members of the CSR Advisory Committee (CSRAC) and
thanked them for attending the meeting. She then asked Dr. Ellie
Ehrenfeld, CSR Director, to present her update. Dr. Ehrenfeld noted that
this would be a short meeting to consider a few important issues. The
agenda for the next CSRAC meeting in September 2002 will be full and
more varied.

**CSR Update**

*New Director for the National Institutes of Health (NIH)*

Dr. Ehrenfeld explained that Dr. Elias Zerhouni has just started work as
the new NIH Director. He previously was the Head of Radiology and the
Executive Vice Dean at The Johns Hopkins University School of Medicine.
Dr. Zerhouni has had an impressive research career in developing and
utilizing imaging technology. He also has served as a CSR reviewer.

*CSR Review Internship Program*

CSR received eight applications for its Review Internship Program this
year and has offered internships to four NIH intramural researchers. Two
of them will enroll in the program. In the previous year, CSR received
30 applications and enrolled four intramural researchers.

Dr. Ehrenfeld said that CSR may have saturated the market for intramural
researchers. It is now considering opening up its internship program to
researchers outside NIH. CSRAC members may be asked for assistance in
developing a plan to expand this program.

*Bioterrorism Initiative*

The President has requested that the National Institute of Allergy and
Infectious Diseases (NIAID) receive a very large amount of money for
biodefense research. CSR anticipates review needs in this area will
increase significantly. NIAID already has issued two biodefense
solicitations. It has received 182 applications for small business
grants for the Development of Rapid Diagnostics and Novel Treatments,
Prevention Strategies, and Screening Methodologies for Anti-Microbials
and Anti-Toxins. NIAID also received 297 applications for a biodefense
Request for Applications (RFA) issued through its Rapid Response Grant
Program. CSR will review the small business grants while NIAID will
review the others. Additional initiatives are expected, and CSR and
NIAID are working together to define their respective review
responsibilities in this area. CSR and NIAID also are recruiting
additional Scientific Review Administrators (SRAs).

*National Institute of Biomedical Imaging and Bioengineering (NIBIB)*

NIBIB has issued its first two RFAs, and CSR will manage reviews for
them in June 2002. Fifty applications were received in response to the
first RFA: Research and Development of Systems and Methods for Molecular
Imaging. Eighty-eight applications were received in response to the
other RFA: Sensor Development and Validation. CSR will manage all of
NIBIB\'s reviews until it becomes more firmly established. Dr. Ehrenfeld
added that Dr. Roderic I. Pettigrew was recently recruited to be the
Director of this new Institute.

*Electronic Review Systems*

[Internet Assisted Peer Review System]{.underline}: 142 of CSR\'s 154
regular standing study sections are using this system to submit their
critiques before their meetings so that other reviewers and the SRAs can
see them ahead of time. Use of the system has been voluntary. It has,
however, proved popular with reviewers, and there is a general feeling
that it has improved the quality of the review process.

[CDs for distributing applications to reviewers]{.underline}: Reviewers
in approximately 50 study sections now receive CDs that contain copies
of the applications to be reviewed. The CDs replace the large box of
applications previously sent to them; however, they still receive hard
copies of their assigned applications. CSR has polled these reviewers
and found that they rate the CDs favorably once they become familiar
with them. Reviewers like the ability to search and navigate quickly
through applications. They also indicate that they are now becoming more
familiar with applications they are not assigned, and their meeting
discussions have improved. CSR will continue to phase in CDs slowly as
the contractor scales up its capacity to produce them.

[Mock study section video]{.underline}: CSR continues to advance efforts
to produce a video of a mock study section to educate new reviewers and
applicants about the peer review process. A draft script has been
produced, and the video may be available in September 2002.

*New General Medicine Study Section*

Dr. Ehrenfeld discussed CSR\'s plans to split the General Medicine A
(GMA) Study Section into two study sections. Over the last 3 years, the
number of applications assigned to GMA has increased markedly, with GMA
reviewing between 90 to 145 applications per round. The Working Groups
that evaluated CSR Integrated Review Groups (IRGs) noted that study
sections that regularly review more than 90 applications a round do not
function well. Dr. Ehrenfeld then explained how the Digestive Sciences
IRG Study Section Boundary Team recommended that GMA be divided before
the overall CSR reorganization occurred. The team proposed that one
study section cover basic and clinical research related to
gastrointestinal hepatobiliary and pancreatic physiology and
pathobiology. A second study section would cover cell/molecular biology
and physiology in the gastrointestinal tract. CSR is thus working to
develop these study sections to review applications submitted for the
October/November 2002 receipt dates. Relevant research communities will
be informed of this change via e-mail, CSR\'s Web site, and discussions
at professional society meetings.

*Application Format Compliance*

Progress has been made in improving compliance with font size and
spacing requirements. CSR is now only returning 2 percent of the
research grant applications it receives because of format problems. The
return rates for other applications, however, have not improved.
Currently, 7-8 percent of the Small Business Innovation Research (SBIR)
applications and 10 percent of the fellowship applications submitted are
returned because of format problems. Applicants are given 4 days to
correct these problems, and only a small number of applications are
deferred to the next review round. Dr. Ehrenfeld explained how CSR
intends to develop outreach activities to educate applicants about
format requirements.

**Implementation Issues in Reorganizing CSR**

Dr. Michael Martin, Director, CSR Division of Physiological Systems,
discussed three stages of CSR\'s reorganization: (1) developing a broad
outline for new IRGs, which was done by the Panel on Scientific
Boundaries for Review (PSBR); (2) designing new IRGs and their study
sections, which is being done by Study Section Boundary (SSB) Teams; and
(3) conducting a concept review of SSB Team recommendations. He noted
that CSR is two-thirds of the way through the design stage, and it is
beginning the third stage by conducting a concept review of the proposed
guidelines for the Hematology IRG. Members of the hematology community
already have provided comments on these guidelines via the Web. CSR has
since worked with NIH staff and community representatives to refine
them. CSRAC was asked to further review these guidelines.

To prepare CSRAC members for this review, they were given a number of
documents before the meeting: (1) the original PSBR IRG recommendations,
(2) the IRG guidelines produced by the Hematology SSB Team, (3) a
summary of public comments, (4) a list of shared interests with other
IRGs, and (5) proposed modifications to the Hematology guidelines. Dr.
Martin encouraged CSRAC to review the proposed guidelines for how well
they would work at both the IRG and study section levels. At the IRG
level, the guidelines should be evaluated for how well they follow the
original PSBR recommendations. CSRAC may determine if any differences
are appropriate. The guidelines also should be evaluated for how well
they articulate areas of shared interest with other IRGs. At the study
section level, the guidelines need to be evaluated for how well they (1)
capture a range of scientific disciplines without being too broad or too
narrow,

\(2\) cluster clinical research appropriately, (3) provide sufficient
overlap with other study sections in the IRG, and (4) provide a venue
for reviewing basic science in the context of the biological questions.

*Overlapping and Shared Areas*

Based on comments by the community and NIH staff, CSR identified five
significant areas included in the proposed Hematology IRG that overlap
with or are shared by other IRGs:

\(1\) parasite infections, (2) lymphocyte biology and lymphopoiesis, (3)
graft versus host disease, (4) gene therapy, and (5) vascular biology.
Dr. Martin explained that the structure and function of membranes and
proteins as well as the function of cells that use blood as source
material are areas included in two IRGs that have not yet been designed:
the Biological Chemistry and Macromolecular Biophysics IRG, and the
Molecular Approaches to Cell Function and Interactions IRG. In addition,
overlap and shared interests exist with four recently designed IRGs.
Apoptosis and cell cycle in blood elements are areas included in the
Biology of Development and Aging IRG. Material surfaces and their
interaction with cells are areas included in the Fundamental
Bioengineering and Technology Development IRG. The interaction of cells
with devices to treat cardiovascular disease and the interactions of
blood cells with the vascular wall are areas included in the
Cardiovascular Sciences IRG. Pathogenesis of leukemias and lymphomas,
bone marrow transplantation, and angiogenesis are areas included in the
Oncological Sciences IRG. Finally, stem cells are covered by many IRGs.

Dr. Martin then discussed proposed modifications to the Hematology
guidelines that better define these areas of overlap and shared
interests. He also proposed adding a paragraph at the beginning of the
document, explaining that the guidelines may be modified further as
additional IRGs are designed and developed.

*Assessment of the Hematology Guidelines*

[Not too narrow or too broad]{.underline}: Dr. Martin said that the
guidelines call for the creation of three thematic study sections: HEM A
covers hemoglobin, erythrocyte, and granulocyte biology; HEM B covers
hematopoiesis and stem cell transplantation; and HEM C covers
hemostasis, thrombosis, and platelets.

[Overlap with study sections within and outside the IRG]{.underline}:
There is limited overlap among these three study sections, while the
current two Hematology study sections cover nearly identical areas. The
Hematology SSB Team emphasized the importance of having study sections
with sufficient depth, and the community appears to support this
decision. The overlap that exists between the Hematology IRG and other
IRGs is not particularly problematic. Dr. Martin discussed a mock sort
he conducted using a subset of May 2000 application abstracts previously
used in CSR\'s reorganization. Difficulties encountered in referring
applications between the Hematology and Cardiovascular Sciences IRGs led
to the development of a shared interest statement for these two IRGs.

[Home for basic science]{.underline}: A significant number of basic
science applications will go to this IRG. A majority of them will be
reviewed in the HEM A study section.

[Clustering of Clinical Research]{.underline}: Very few clinical
research applications are submitted in the areas served by the
Hematology IRG. Any of these applications that require evaluation by a
biostatistician are particularly problematic. The SSB Team recommended
that these applications be reviewed elsewhere, either in a clinical
cardiovascular study section or a special emphasis panel. Dr. Martin
noted the difficulty of placing these applications in the Cardiovascular
Sciences IRG. Cardiologists and hematologists do not significantly share
the same areas of interest that would enable them to have a mutual
appreciation for the relative scientific merits of their respective
applications.

CSRAC members were encouraged to consider these issues in making their
final recommendation on the Hematology IRG guidelines. Dr. James Kushner
said that he had discussed the proposed guidelines with study section
members as well as colleagues at other hematology divisions. He has
concluded that the proposed study sections were well-defined, and he
recommended that CSRAC approve the draft guidelines with the
understanding that some fine tuning may be necessary later. Dr. Michael
Colvin also discussed the proposed guidelines with his colleagues in the
hematology community, and he agreed that the guidelines should be
approved.

Dr. Matthews then focused on how well the Hematology IRG guidelines met
the criteria

Dr. Martin proposed for evaluating them. She said that everyone appeared
to agree that the breadth of science covered by the IRG was not too
broad or narrow. The shared interests with other IRGs were clearly
articulated, and there was sufficient overlap with other IRGs.

Dr. Matthews continued by saying that it was appropriate for the few
clinical research applications in this area to be assigned to another
scientific review group. She then noted that the proposed IRG provided
an appropriate home for the basic sciences.

Dr. Kushner made a motion for CSRAC to approve the Hematology IRG
guidelines, and CSRAC members unanimously agreed to approve them.

*Implementation Issues and Concerns*

Dr. Martin discussed two approaches to implementing the new IRG
guidelines. He called the first one the \"begin at the beginning\"
approach, whereby individual IRGs are implemented gradually as they are
approved. The alternative approach is to implement the IRGs all at once
after the last one is approved. He called this latter approach the
\"Swedish driving\" approach, referring to how Sweden, on one day,
switched the side of the road cars drive on.

The upsides of the gradual approach are that (1) CSR could conduct
focused and targeted outreach, (2) the referral office would have a
limited number of changes to address at one time, (3) only a small
number of regular reviewers and SRAs would have to move at once, (4) the
Committee Management Office would not be overwhelmed processing the
changes, and (5) CSR could learn as it goes. Potential downsides are
that (1) some applications that would have been reviewed by the parent
IRG might be directed to an IRG that has not yet been formed, (2) an IRG
that has not yet been reorganized might still provide a home to some
applications that should be moved to the new IRG, (3) applicants might
be uncertain about which study section should review their applications,
(4) referral guidelines would change from round to round, and (5) more
and more interim study sections would be needed to deal with
applications that become temporarily homeless.

Dr. Martin then discussed the upsides of the all-at-once approach: (1)
no interim study sections would be needed, (2) the outreach effort would
be uniform/global, (3) applicants would have a uniform set of review
options, (4) the referral office would have one set of stable
guidelines,

\(5\) reviewers and SRAs would have defined homes, and (6) the range of
science reviewed would be more consistent and scoring would be more
stable. As for the downsides, he noted that the referral office, the
Committee Management Office, reviewers, and SRAs would have difficulty
adjusting to a sudden organizational change in a short time frame.

In discussing the timing of the implementation, Dr. Martin indicated
that the all-at-once approach would delay the implementation of many
IRGs, and the reorganization would not be complete until October 2004 or
later. With the begin-at-the-beginning approach, the first IRG would
meet in June 2003, and the last IRG would meet in October 2004 or later.
In addition, interim study sections will be necessary for four or more
rounds to deal with applications caught in the transition.

Dr. Kushner said that he had always thought CSR would take the gradual
approach and form interim structures until the reorganization is
complete. He continued by saying that the all-at-once approach seemed
overwhelming. Dr. Matthews noted that there was a lot of enthusiasm and
acceptance for change, and many community members would be disappointed
if the reorganization of their area was delayed. She then asked how many
IRGs were ready for implementation. Dr. Martin explained that CSR is
seeking to conduct a second mock sort of applications from a more recent
review round, and there may be three IRGs ready for CSRAC review in
September 2002, and more to review in January 2003. Dr. Matthews then
endorsed the idea of implementing the simplest and least problematic
IRGs first.

Dr. Michael Leon said that the begin-at-the-beginning approach would be
difficult, but the all-at-once approach would be impossible to
implement. He emphasized the value of taking a step-by-step approach and
applying lessons learned along the way. Dr. Pugh focused on the
potential problems an all-at-once approach could cause for
investigators. Many applications may be sent to the wrong study section
or fall through the cracks, causing a delay of one review cycle.

Dr. Matthews summarized the discussions by saying that CSRAC members
appeared to favor the gradual approach to implementing the new IRGs. She
then explained how this discussion has renewed her appreciation for
CSR\'s reorganization efforts.

**Senior Reviewers**

Dr. Ann Hardy, SRA, CSR Social Sciences, Nursing, Epidemiology and
Methods 5 Study Section, presented recommendations on establishing a
senior reviewer category. She represented a CSR staff committee
established by Dr. Ehrenfeld to develop these recommendations.

Dr. Hardy defined a senior reviewer as a very senior researcher in a
given field who can bring a broad perspective to reviews as well as help
train new reviewers. Senior reviewers would be offered a reduced term of
service, which could help some SRAs recruit more senior scientists.

*Eligibility*

Dr. Hardy then described the proposed eligibility requirements for
senior reviewers. They must have completed a term of review service, be
a recognized leader in their field, possess a strong track record of
grant support and publications, and be active researchers. Senior
reviewers also should have a broad view of the field and a vision for
the future, as well as have good communications skills and the ability
to work well with others.

*Responsibilities*

Senior reviewers could be given different responsibilities to meet
different needs. For instance, they could attend initial meetings each
year to help train new reviewers, review the first few applications at
their meetings to demonstrate how reviews should be focused, or only
read the applications and help focus discussions. Senior reviewers would
be offered shorter terms of service, e.g., 3 years instead of 4 years.

*Recruitment*

Dr. Hardy explained that senior reviewer candidates could be recruited
from the ranks of retired study section members. CSR also could solicit
nominees from professional groups and NIH Institute staff, as well as
from study section chairs and members.

*Implementation Considerations*

The CSR senior reviewer committee recommends that SRAs and their study
sections have the option of deciding whether or not to recruit a senior
reviewer for their group. SRAs should actively solicit nominations from
many sources, but they should make the final decisions on recruiting a
senior reviewer. Interested SRAs also should assess the interest of
retiring members. In addition, Dr. Hardy\'s committee recommends that
CSR conduct a pilot test with two volunteer study sections from each
division and from different IRGs. Feedback could be collected from the
SRAs, chairs, members, observers, and professional groups, as well as
from the senior reviewers. To publicize this effort, CSR should first
inform CSR staff, and then the SRAs should inform their study section.
In disseminating information to external groups, CSR could use the *Peer
Review Notes* newsletter, a press release, and a Web notice. Notices
could also be given to Institute/Center advisory councils and to
professional groups. Dr. Hardy explained that her committee did not
reach consensus on the title to be given to senior reviewers. She
explained that the title should highlight the unique role and
characteristics of these reviewers without having any negative
connotations or making other members seem less important. Preferred
titles were \"Special-Term Reviewer,\" \"Executive Reviewer,\"
\"Consulting Reviewer,\" \"Advisory or Senior Advisory Reviewer,\" or
\"Director\'s Reviewer.\" These reviewers could also be called a \"Named
Reviewer,\" e.g., \"Varmus Reviewer.\"

Dr. Leon began discussions by saying that the concept of creating a
category for senior reviewers was a good one. He emphasized the value
these individuals could have in setting the proper tone for review
discussions and helping junior reviewers take a more broad and positive
approach. Dr. Leon suggested that senior reviewers attend every study
section meeting, but they need not be responsible for reviewing grants
themselves. He also suggested that some researchers with long and
distinguished careers could be effective senior reviewers even if they
are not actively conducting research or holding an NIH grant. Dr. Pugh
said he concurred with many of the points raised. He suggested that CSR
could further define the responsibilities of the senior reviewers. For
instance, they could serve the study section chair in various ways and
also provide valuable input on assigning applications to study section
members. He proposed that these reviewers not vote but serve in an
advisory role. Dr. Pugh also emphasized the value of involving
scientific communities in ways that would confer distinction to those
selected to be senior reviewers.

Dr. Kushner suggested that senior reviewers could have a greater impact
in setting the proper tone at a study section meeting if they reviewed a
grant and proposed a score. Dr. Susan Berget agreed, and added that
senior reviewers could be particularly helpful in reviewing problematic
grants. She continued by saying that scientists who no longer run a
laboratory cannot keep pace with rapid advancements in their field and
should not be senior reviewers, although she said that it may not be
necessary for them to hold an NIH grant. Dr. Leon agreed that active
researchers would be more qualified, but he suggested that CSR consider
loosening its recruitment standards if necessary to fill particular
needs.

Dr. Colvin returned to the role senior reviewers could play by saying
that it would be difficult for them to provide a broad perspective on a
grant without reviewing it, although they could still be helpful just
listening to the review discussions. Dr. Leon proposed giving the SRAs
the flexibility to determine the role a senior reviewer might play in
each meeting. Dr. Pugh suggested that CSR consider conducting an
experiment with some senior reviewers reviewing grants and others just
reading them.

Dr. Matthews added her support to this initiative. She emphasized the
value of allowing SRAs and study section chairs flexibility in using
senior reviewers. She also emphasized the role these individuals could
play in setting the tone of review meetings. The easiest way for these
individuals to be effective, however, would be for them to review grant
applications and teach by example. As for naming this category of
reviewers, Drs. Matthews and Kushner recommended the term \"Director\'s
Reviewers.\" Drs. Leon and Pugh earlier recommended the term \"Senior
Advisory Reviewers.\" Dr. Matthews concluded her comments by saying
that, despite a range of perspectives, CSRAC members would like CSR to
proceed in developing this mechanism for involving more senior
scientists in the review process. She then asked Dr. Hardy if she had
all the feedback she needed.

Dr. Hardy asked for input on whether or not CSR should conduct a pilot
first. Dr. Ehrenfeld explained that a pilot could be useful in allowing
CSR to learn how best to use senior reviewers. She added that she would
like to see these reviewers be listed on study section rosters.

Dr. Ehrenfeld then suggested that Dr. Hardy\'s committee work to
delineate the responsibilities of these reviewers and those of the study
section chairs. It is important that there is no overlap or competition.
Dr. Kushner said that it also was important that this initiative not
disrupt the effective study section culture. He thus supported
proceeding with a pilot and allowing SRAs and chairs to decide whether
or not their study sections could benefit from having a senior reviewer.
He then asked Dr. Ehrenfeld who would approve nominations for this
category of reviewers. She suggested that the boards of related
professional societies could be involved in vetting nominees; however,
she proposed that Dr. Hardy\'s committee explore this issue further. Dr.
Matthews concluded the discussion by saying that CSRAC was very
interested in hearing how this initiative develops.

**Meeting of the Human Pluripotent Stem Cell Review Group**

Dr. Matthews introduced Dr. Wendy Baldwin, NIH Deputy Director for
Extramural Research. She is also the Executive Secretary of the Human
Pluripotent Stem Cell Review Group (HPSCRG). Grant applications that
propose to use human pluripotent stem cells derived from human fetal
tissue are reviewed by this group to ensure that these cells were
developed in accord with the NIH guidelines. Dr. Baldwin noted that
there was a major policy change in August 2001, when President Bush
announced new guidelines for using human embryonic stem cells in
federally funded research. While his policy superseded previous NIH
guidelines, it did not do away with NIH procedures for determining the
acceptability of using human stem cells derived from fetal tissue. Dr.
Baldwin explained that HPSCRG was being convened to review a relevant
application that the National Institute of Diabetes, Digestive and
Kidney Diseases (NIDDK) is seeking to fund. HPSCRG is required to meet
in an open meeting of CSRAC and to submit its recommendation to CSRAC
members for concurrence/non-concurrence. Dr. Baldwin noted that this
application has already been reviewed for scientific merit. HPSCRG will
only consider whether the materials submitted by the applicant
demonstrate that the stem cells derived from fetal tissue comply with
the NIH guidelines.

The following HPSCRG members were present: Dr. Richard Nakamura, Acting
Director of the National Institute of Mental Health; Dr. Christine
Grady, Head of the Section on Human Subjects Research at the NIH
Clinical Center; and Dr. Joan McGowan, Director of the Musculoskeletal
Diseases Branch at the National Institute of Arthritis and
Musculoskeletal and Skin Diseases. Two other HPSCRG members participated
via a conference call: Dr. Duane Alexander, HPSCRG Chair and Director of
the National Institute of Child Health and Human Development; and Dr.
Larry Tabak, Director of the National Institute of Dental and
Craniofacial Research. One HPSCRG member recused himself because of a
conflict of interest with the application: Dr. Griffin Rogers, NIDDK
Deputy Director.

Dr. Alexander then convened the HPSCRG meeting to review an application
submitted by

Dr. Michael Shamblott at The Johns Hopkins University: \"Glucose
Responsive Insulin Producing Cell Lines.\" Dr. Alexander explained that
this application was special because the cell line proposed for use was
derived in 1999, which was before the development of the NIH guidelines
and before the term \"pluripotent\" had been coined. As a result, HPSCRG
will need to closely consider the submitted materials to ensure
compliance with the intent of the guidelines. He noted that the
guidelines contain eight review criteria and suggested that HPSCRG
consider them individually. For each criteria, an HPSCRG member was
asked to determine if the information provided by the applicant
addressed the criteria and whether this information was acceptable
according to the guidelines.

1\. An assurance signed by the responsible institutional official
indicating that the pluripotent stem cells were derived from fetal
tissue in accord with Section II. B.2 of the guidelines and that the
institution will maintain supporting documentation.

> Dr. Nakamura said that such a letter was provided and he found it
> acceptable. HPSCRG members concurred.

2\. An assurance that the stem cells to be used were obtained through a
donation or a payment that does not exceed the reasonable cost of
transporting, processing, preserving, controlling for quality, and
storing them. Dr. Nakamura said that both the institution and the
principal investigator (PI) submitted relevant and acceptable materials.
HPSCRG members agreed.

3\. An assurance that the proposed research was not one of the types
listed as ineligible for funding in Section III of the guidelines. Dr.
Nakamura and the other HPSCRG members agreed that both the institution
and the PI provided the appropriate assurances.

4\. An abstract of the scientific protocol used to derive the stem cells
from fetal tissue.

> Dr. McGowan explained that the PI submitted the actual protocol, an
> additional description, and two articles published in the *Proceedings
> of the National Academy of Sciences* that describe the derivation of
> the cells and the embryonic bodies. All HPSCRG members agreed that
> these materials met the requirement.

5\. The title of the research proposal or specific subproject that
proposes the use of human pluripotent stem cells. Dr. McGowan noted that
the required title was provided: \"Glucose Responsive Insulin Producing
Cell Lines.\"

6\. Written consent from the PI permitting the public disclosure of
submitted materials necessary to carry out the public review and other
oversight procedures described in Section IV of the guidelines. Dr.
McGowan and HPSCRG members agreed that written consent was provided and
that it was acceptable.

7\. A sample informed consent form (with patient identifier information
removed) and a description of the informed consent process that meet the
criteria for informed consent described in Section II.B.2 of the
guidelines.

> a\. A statement that fetal tissue will be used to derive human
> pluripotent stem cells for research that may include human
> transplantation research. Dr. Grady noted that the term \"human
> pluripotent stem cells\" was not used at the time, and the consent
> form therefore does not use it. Dr. Grady, however, emphasized that
> the consent form clearly states that the donated tissue would be used
> for research and it could be transplanted for therapeutic purposes.
> She continued by saying that the common understanding of
> transplantation is that tissues would be put in another person, grown
> in that environment for a long time, and not be given back. Dr. Grady
> therefore found that there was sufficient reason to conclude that the
> guideline for appropriate informed consent was met. HPSCRG members
> accepted Dr. Grady\'s interpretation and concurred that adequate
> consent was provided.
>
> b\. A statement that the donation was made without any restriction or
> direction regarding the recipients of transplantation of the cells
> derived from fetal tissue. HPSCRG members all agreed that these
> requirements were met.
>
> c\. A statement as to whether or not information that could identify
> the donors of the fetal tissue, directly or through identifiers linked
> to them, was removed prior to the derivation or use of the cells. Dr.
> Alexander explained that the submitted consent form did not mention
> patient identifiers; however, a form signed by the attending physician
> stated that the physician disclosed any known risk to the patient,
> including risk to her privacy associated with her donation or patient
> care. In addition, institutional officials provided a statement saying
> that researchers and collaborators did not have access to the codes
> linking specimens and patients. These codes are maintained by the
> institutional review board (IRB).
>
> Dr. Alexander concluded that there was sufficient documentation to say
> that the intent of this requirement was met. HPSCRG members concurred.
>
> d\. A statement informing donors that derived cells and/or cell lines
> may be kept for many years. Dr. Alexander noted that the informed
> consent document did not include such wording. However, it mentions
> transplantation, which is a long-term or permanent event. He suggested
> that donors could thus anticipate that the donated cells would be
> maintained for many years. Dr. Alexander asked HPSCRG members if they
> agreed with his interpretation. All the members concurred.
>
> e\. Disclosure of the possibility that the results of research on
> human pluripotent stem cells may have commercial potential and that
> the donor would not receive any financial or other benefits. Dr. Tabak
> explained that the consent document stated The Johns Hopkins
> University would receive the financial benefits of any scientific or
> medical inventions that resulted from the research. Dr. Tabak and the
> other HPSCRG members agreed that this statement was sufficient.
>
> f\. A statement that the research is not intended to provide direct
> medical benefit to the donor. Dr. Tabak explained that the consent
> document stated that the donation was made with no restriction
> regarding the recipient of the tissue. This statement would also apply
> to the donor, therefore, donors would understand that they would not
> gain any direct medical benefits. HPSCRG members agreed that this was
> an acceptable interpretation.

8\. Documentation indicating that the derivation protocols were approved
by an IRB established in accord with the Code of Federal Regulations (45
CFR § 46.107) or those established by the Food and Drug Administration
(21 CFR § 56.107 and § 56.108).

> Dr. Alexander stated that an acceptable letter from an IRB at The
> Johns Hopkins University was provided. HPSCRG members concurred.

*Final Review*

Dr. Alexander noted that, in most instances, the submitted materials
complied with the letter of the guidelines. In the other instances, the
submitted materials complied with the intent and spirit of the
guidelines sufficiently for the group to find them acceptable. He then
moved that HPSCRG agree (1) the derivation process used in developing
the pluripotent stem cell lines from fetal tissue proposed for use by
Dr. Michael Shamblott met the criteria required by the NIH guidelines,
(2) the submitted materials were acceptable, and (3) the HPSCRG should
forward a recommendation of acceptance to CSRAC. Dr. Tabak seconded the
motion, and the remaining HPSCRG members concurred.

Dr. Kushner began CSRAC discussions by focusing on HPSCRG\'s conclusion
that donors consented to maintaining the stem cells for an extended time
based on their consent to the possibility that their cells might be
transplanted into other individuals. He noted the difference between
long-term placement of cells in another individual and culturing cells
for a long time in a laboratory. Dr. Grady said that she found both uses
acceptable based on the understanding that donors knew that the donated
cells would be \"gone\" from their control and used for research and
transplantation, and that an unknown number of things might be done with
them. Dr. Kushner added that it would be reasonable to expect the cells
to be cultured over a long term, given the small size of the tissue
donation and the understanding that the cells would be transplanted into
adults. Dr. Nakamura emphasized the significance of the fact that donors
were informed that the cells would be transplanted into multiple
individuals. Dr. Kushner agreed and noted that any reasonable person
would understand that multiple transplants would require expansion of
the cells in the laboratory. Dr. Pugh focused on how well donors may
have understood that they would not gain any financial benefit. Dr.
Kushner said that the word \"donation\" used in the consent form implied
that the donor was making a gift and that no financial gain could be
expected. Dr. Grady agreed, but she noted that the field has evolved
since 1999 and consent forms are now more explicit.

Dr. Matthews asked CSRAC members if they had any further comments. When
no more were made, Dr. Kushner moved that CSRAC concur with the HPSCRG
recommendation to accept the documents submitted in support of the
proposal entitled \"Glucose Response Insulin Producing Cell Lines.\" Dr.
Pugh seconded the motion and the rest of the CSRAC members concurred.

Dr. Baldwin said that a summation of HPSCRG\'s recommendation would be
submitted to CSR so that it could be forwarded to NIDDK, the funding
Institute. Dr. Matthews thanked

Dr. Baldwin and members of the HPSCRG for their contributions.

**Approval of the January 2002 CSRAC Minutes**

Dr. Colvin moved that the CSRAC approve the minutes from the January
28-29, 2002, CSRAC meeting. The Committee approved them without comment.

**Agenda Items for the Next Meeting**

Dr. Matthews reviewed possible agenda items for the next meeting: (1)
review of three to four IRG guidelines, (2) useful practices for making
streamlining work, (3) training and selecting study section chairs, (4)
defining and identifying new investigators, (5) CSR contingency plans
for emergencies, (6) update on the innovation initiative, (7) mock study
section video,

\(8\) longevity and retention of PIs, (9) format options for reviewing
applications that involve the use of human and animal subjects and the
recruitment of women and minorities, (10) addressing the special needs
of postdoctoral applicants, (11) shortening the review cycle so
applicants can resubmit for the next round, (12) developing guidelines
for review of plans for sharing of data, and (13) review of new
assurance documents for proposals to use embryonic germ cells.

Dr. Matthews concluded the meeting by noting that this would be Dr.
Kushner\'s last meeting and acknowledging his invaluable contributions
to the Committee over the years.

With no other business to address, Dr. Matthews thanked everyone for
their efforts and adjourned the meeting at 2:25 p.m.

We do hereby certify that, to the best of our knowledge, the foregoing
minutes are accurate and complete. The minutes will be considered at the
30th meeting of the Advisory Committee, and any corrections or comments
will be made at that meeting.

> \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
>
> Brent Stanfield, Ph.D.
>
> Executive Secretary
>
> Center for Scientific Review Advisory Committee
>
> \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
>
> Ellie Ehrenfeld, Ph.D.
>
> Director
>
> Center for Scientific Review
>
> \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
>
> Karen Matthews, Ph.D.
>
> Chair
>
> Center for Scientific Review Advisory Committee