Guidelines for Use of Stored Specimens and Access to Ancillary Data and Proposed Cost Schedule: Stored Biologic Specimens and Ancillary Data From the Collaborative Perinatal Project (CPP), 66110-66113 [2010-27183]

Agencies

• DEPARTMENT OF HEALTH AND HUMAN SERVICES
• National Institutes of Health

[Federal Register Volume 75, Number 207 (Wednesday, October 27, 2010)]
[Notices]
[Pages 66110-66113]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-27183]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Guidelines for Use of Stored Specimens and Access to Ancillary 
Data and Proposed Cost Schedule: Stored Biologic Specimens and 
Ancillary Data From the Collaborative Perinatal Project (CPP)

ACTION: Notice and request for comments.

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SUMMARY: The Division of Epidemiology, Statistics and Prevention 
Research (hereafter, Division) of the Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD) maintains an 
extensive repository of datasets from completed studies, biospecimens, 
and ancillary data. The Division intends to make datasets and 
biospecimens more widely available to the research community for use by 
qualified researchers and to establish procedures for access consistent 
with the National Institutes of Health (NIH) Data Sharing Policy. The 
Division has established an internal committee, the Biospecimen 
Repository Access and Data Sharing Committee (BRADSC), to oversee the 
repository access and data sharing program. The purpose of this notice 
is to request comments on this program and present the initial proposed 
cost schedule. After full consideration of comments submitted in 
response to this notice, the BRADSC will finalize proposal guidelines 
and procedures, publish the cost schedule to the Division Web site, and 
begin to accept proposals for use of the stored biologic samples and 
for access to ancillary data that may not be available electronically. 
The first specimens and ancillary data that will be made available 
under this program are those from the national Collaborative Perinatal 
Project (CPP).
    The CPP is a large, prospective cohort study, conducted by the 
National Institute of Neurological Diseases and Stroke (NINDS) of the 
National Institutes of Health (NIH), which recruited and enrolled 
48,197 women who contributed 54,390 pregnancies that were prospectively 
followed from 1959-1966 at twelve academic medical centers across the 
United States. Custody for disposition of the CPP serum specimens was 
transferred to the Division from the NINDS in 1993 and for the 
microfiche archives in 1999. However, under the Federal Privacy Act of 
1974 the samples and archive still belong to NINDS. Since 1992, the 
specimens have had limited public availability through Division 
investigators. Going forward, the Biospecimen Repository Access and 
Data Sharing Committee (BRADSC) will oversee the repository access and 
data sharing program. Access to other Division resources will be 
announced on the Division Web site. The BRADSC reserves the right to 
amend the procedures and costs schedules as necessary to maintain the 
integrity of the program and to suit the conditions under which other 
specimens were collected. Announcements and current proposal guidelines 
will be available under the Research link at https://despr.nichd.nih.gov, and interested researchers should consult the 
Division Web site for resources available, the most recent guidelines 
for proposal submission and evaluation, and cost schedules. Procedures 
may vary depending on the age and nature of the samples and original 
institutional review board (IRB) approval, although the general outline 
of the procedures should remain the same. Cost schedules may vary 
depending on the nature and complexity of the request.
    No funding is provided as part of this notice nor will any be 
available as part of the program either to support laboratory analyses 
or data management. Samples will only be provided to approved projects 
upon receipt of evidence of necessary IRB approval(s), funding and 
payment of repository costs and shipping. Approved projects that do not 
obtain funding will be canceled within one year of their approval date. 
A more complete description of this program follows. Comments or 
requests for clarification on all aspects of the program are welcome.

DATES: 
     Comment Receipt Date: December 15, 2010.
     Invitation to Submit Proposal: Proposals can be submitted 
on an ongoing basis.
     Scientific Review Dates: Technical Panels for reviews will 
be assembled beginning on January 1, May 1, or September 1 of the 
calendar year so that proposals can be evaluated well in advance of 
Federal funding deadlines.
     Anticipated Distribution of Samples: Within one month of 
demonstrable proof of applicant IRB approval and receipt of payment to 
cover repository costs and shipping.

ADDRESSES: To send comments and to request information, contact: Dr. 
Mary L. Hediger, Division of Epidemiology, Statistics and Prevention 
Research, Eunice Kennedy Shriver National Institute of Child Health and 
Human Development, 6100 Executive Blvd,

[[Page 66111]]

Room 7B03, MSC 7510, Rockville, MD 20852, Phone: 301-435-6897, E-mail: 
hedigerm@exchange.nih.gov.

SUPPLEMENTARY INFORMATION: 
    The Collaborative Perinatal Project (CPP): The major stated aims of 
the CPP were to: (1) Determine the relationship between factors in the 
perinatal environment and the continuum of human reproductive failure, 
with particular reference to the central nervous system (CNS) for early 
(infancy and early childhood) and later (childhood) manifestations of 
deficits; (2) study the effect of the extra-uterine environment on 
fetal development (e.g., socio-economic factors, family structure); (3) 
determine the relationship of prematurity to factors in the perinatal 
environment and the continuum of human reproductive failure, with 
particular reference to the CNS; (4) study the clinico-pathological 
correlations in the continuum of human reproductive failure, with 
particular reference to the CNS; and (5) improve the classification, 
treatment and prevention of cerebral palsy. The Collaborative Perinatal 
Project (CPP) enrolled 48,197 women who contributed 54,390 pregnancies 
that were prospectively followed from 1959-1966 at twelve academic 
medical centers across the United States, including hospitals in 
Baltimore MD, Boston MA, Buffalo NY, Memphis TN, Minneapolis MN, New 
Orleans LA, New York NY (2 sites), Philadelphia PA, Providence RI, 
Portland OR, and Richmond VA. The women were recruited generally in the 
second trimester of pregnancy and followed through delivery. The 
children were followed periodically to seven or eight years of age. 
Data collection was concluded in 1974, and data were stored on computer 
tapes in ``card image'' format (80 columns/card).
    A wide range of data was collected using standardized protocols and 
forms, including socio-demographic, obstetric, pediatric, infant 
neurological, and child psychological information. Electronic data 
files, forms, and documentation are available and accessible in the 
public domain. The CPP collected serum samples at recruitment, every 
eight weeks thereafter during pregnancy, and at the time of the 
delivery hospitalization. Cord blood was collected from approximately 
60 percent of the infants, and some serum samples are available from 
women at six weeks postpartum. Residual serum and cord blood samples 
have been stored continuously in glass vials at -20 [deg]C since 
collection, are inventoried, and are linkable to individual electronic 
records by the original CPP identification number. A microfiche archive 
is also stored and available, compiled by identification number, and 
containing CPP completed forms and records with ancillary information, 
original medical notes, and comments.
    In 1983, electronic data files, forms, and documentation were 
compiled from the original tapes and manuals, documented, and written 
to other media. The data and documentation are currently available and 
accessible in the public domain (e.g., https://www.nber.org/cpp/docs/). 
In addition to the files available electronically, the CPP collected 
serum samples at recruitment, subsequently every eight weeks during 
pregnancy, and at the time of the delivery hospitalization. Cord blood 
was collected from approximately 60 percent of the infants, and some 
serum samples are available from women at six weeks postpartum. 
Residual serum and cord blood samples have been stored continuously in 
glass vials at -20 [deg]C since collection, are inventoried, and are 
linkable to individual electronic records by the original CPP 
identification number. A microfiche archive, compiled by identification 
number containing CPP completed forms and records with ancillary 
information, original medical notes, and comments, is also stored and 
available.
    There are CPP serum samples from at least 53,515 pregnancies from 
46,424 women available for research proposals using CPP samples. There 
are approximately 32,130 samples of cord blood.
    Clinical Significance: Because the CPP samples were collected 
before controlling guidelines were available, participants did not 
consent to future use. Therefore, only research projects that propose 
laboratory results or findings in the ancillary data that do not have 
immediate clinical significance to an individual will be deemed 
acceptable for the CPP. Applicants should address this clearly in the 
research proposal.
    Clinical significance for laboratory studies is defined by the 
following criteria:

The findings are valid and done by a CLIA-certified laboratory; and
The findings may have significant immediate implications for the 
subjects' health concerns; and
A course of action to ameliorate, or treat the concerns is readily 
available.

    Clinical significance for ancillary findings is defined:

The findings may have significant immediate implications for the 
subjects' or their family's health concerns; and
A course of action to ameliorate, or treat the concerns is readily 
available.
    Proposals for Use of the Samples and Access to the Ancillary Data: 
All proposals for use of CPP samples and access to the ancillary data 
will be evaluated by an ad hoc Technical Panel for scientific merit. 
The BRADSC will generally rely on the investigators' approval of the 
proposal by their institutional review board (IRB) for use of the 
samples and access, although the BRADSC reserves the right in 
questionable cases to have the NICHD IRB review the proposal even if 
the investigators have already received approval by their IRB.
    Evaluation Criteria: To determine if the biologic specimens (a 
limited resource) should be used in the proposed projects or if an 
applicant should be given access to the microfiche archives, an ad hoc 
Technical Panel, chosen and overseen by BRADSC and comprised of two 
content and one statistical reviewer, will evaluate the public health 
significance and scientific merit of each proposed research project. 
Applicants may be asked to suggest outside reviewers, but the final 
composition of the Technical Panel will be at the discretion of the 
BRADSC. Scientific merit will be judged as to the scientific, technical 
or medical significance of the research, the appropriateness and 
adequacy of the experimental approach, and the methodology proposed to 
reach the research goals. If the project involves biologic specimens, 
the Technical Panel will also consider the amount of sample requested 
and weigh the significance of the research against the amount of sample 
requested and that remaining. Investigators are encouraged to request 
the smallest amount of sample possible consistent with best scientific 
practices and the aims of their study. The proposal should outline how 
the results from the laboratory analysis or findings from the original 
forms will be used. The appropriateness of the CPP sample to address 
the goals of the proposal will be an important aspect of scientific 
merit. The Technical Panel will review the analysis plan and evaluate 
whether the proposal is an appropriate use of the CPP population and 
likely to be successful. The Technical Panel will also assure that the 
proposed project does not go beyond the specific stated goals of the 
proposal. Investigators are encouraged to review the CPP forms and 
documentation at: https://despr.nichd.nih.gov or https://www.nber.org/cpp/docs/. The Division Web site will also have posted

[[Page 66112]]

accessible copies of pertinent publications on the history of the CPP 
and scientific papers with notable findings.
    Procedures for Proposals: All investigators (including NIH and 
NICHD investigators) must submit a proposal for use of CPP specimens. 
Proposals are limited to a maximum of ten (10) single-spaced typed 
pages, excluding figures and tables, using 12 cpi type density. The 
proposal should be comprehensive and tailored to the request and not 
simply be sections lifted from another Federal or foundation 
application. The cover of the proposal should include the name, 
address, and phone number and e-mail address of the Principal 
Investigator (PI) and the name of the institution where the laboratory 
analysis will be done if they are a component of the project. All 
proposals should be e-mailed to the address specified on the Web site. 
Proposals must include a cover page with the title of the proposal and 
the name, address, phone number and e-mail address of all 
investigators. The following criteria will be used for technical 
evaluation of proposals:
    Proposals should include the following information:
    (1) Specific Aims: List the broad objectives; describe concisely 
and realistically what the research is intended to accomplish, and 
state the specific hypotheses to be tested.
    (2) Background and Public Health Significance: Describe the public 
health significance, scientific merit and practical utility of the 
assay or information. Briefly describe in one or two pages the 
background of the proposal, identifying how the project may also relate 
to previous (published) analyses of the CPP and gaps in knowledge that 
the project is intended to fill. State concisely the importance of the 
research in terms of the broad, long-term objectives and public health 
relevance including a discussion of how the results will affect public 
health policy or further scientific knowledge. The proposer should 
convey how the results will be used and the relationship of the results 
to the data already collected in the CPP. The applicant should include 
an analysis plan. Applicants are encouraged strongly to have a 
statistical consultant or someone knowledgeable about statistics be 
part of the investigative team or nominally review the plan before 
submission. The analyses ought to be consistent broadly with the CPP 
aims and the health status variables.
    (3) Research Design and Methods: Describe the research design and 
the procedures to be used. Data and/or biospecimen requests should 
specify the exact variable(s) or sample name(s) as provided in the CPP 
documentation or give an expectation of findings in notes or other 
forms in the microfiche archive. If there is a laboratory component, a 
detailed description of laboratory methods including validity and 
reliability must be included with references. Because the samples were 
collected over forty years ago, applicants should consider how aging 
might have affected the samples. If no data are available on how aging 
might have affected the samples, a limited number of samples of the 
same historical age are available for pilot studies. Even if the 
proposal is meritorious, the BRADSC may expect, upon advice of the 
Technical Panel, that a pilot be completed before all specimens 
requested are released to the investigators.
    The volume of specimen and number of samples requested must be 
specified. Adequate methods for handling and storage of samples must 
also be addressed. The laboratory must demonstrate expertise in the 
proposed laboratory test including the capability for handling the 
workload requested in the proposal. The proposal should also include a 
justification for determination of study sample size or a power 
calculation. If the researcher is requesting a regional or targeted 
sub-sample of specimens, a detailed description and justification must 
be given. The study design and analysis plan in the proposal will be 
evaluated to determine whether the project is feasible and can be 
performed using the CPP.
    (4) Clinical Significance or Results: Since individual results 
cannot be provided, the clinical significance of the proposed 
laboratory test should be addressed. The proposal should include a 
discussion of the potential clinical significance of the results and 
whether there is definitive evidence that results of the test would 
provide grounds for medical intervention even given that many years 
have passed since the examination of the participant and collection of 
the sample. Any test with results that should be reported immediately 
to a participant is not appropriate for testing on the stored samples.
    (5) Qualifications: Provide a brief description of the Principal 
Investigator and other investigators' expertise in the proposed area, 
including publications in this area within the last three years. A 
representative sample of earlier publications may be listed as long as 
this section does not exceed two pages.
    (6) Period of performance: Specify the project period. Substantial 
progress must be made in the first year, and the project should be 
completed in two years. If additional time is needed for the research 
project a detailed justification with a timeline should be included. 
The investigators should address their ability to comply with this 
timeline or request and justify additional time for the project. Return 
of the specimens will be requested if progress is not made in the 
project at the end of the second year. Refund of payment for the 
specimens will not be returned in this situation. At the end of the 
project period, any unused samples must be returned to the Division 
Repository or discarded, according to the wishes of the BRADSC. Within 
six months to one year of the end of the project period, and consistent 
with NIH Data Sharing guidelines, the investigators will submit to the 
Division for access by the wider research community a complete and 
clean copy of the new data obtained, whether from laboratory analyses 
or the microfiche archives, coded and linkable to the main CPP database 
through the study ID, documentation, and a letter from the PI 
certifying the data.
    (7) Funding: Include the source and status of the funding to 
perform the requested laboratory analysis should be included. 
Investigators will be responsible for the cost of processing and 
shipping the samples. The basis for the cost structure is in the last 
section of this notice. Reimbursement for the samples will be collected 
before the samples are released.
    Submission of Proposals: Proposals can be submitted in MS Word or 
pdf format by e-mail to: hedigerm@exchange.nih.gov.
    Summary of Evaluation Criteria: (1) Relevance of the study question 
to current research; (2) adequacy of the study design to address the 
question; (3) feasibility and appropriateness of the CPP for conducting 
the study; (4) if there is a laboratory component, appropriateness of 
the assay, including evidence that the analyte is stable under 
prolonged storage at -20 [deg]C; and (5) experience of the 
investigators in conducting similar studies, including knowledge of the 
CPP.
    Approved Proposals: Approved projects will be provided specimens 
upon receipt of a check to cover the cost of accessing, preparing, and 
shipping the specimens. Approved projects requesting access to the 
microfiche archives will be granted access once arrangements have been 
made with the Division. Approved and funded projects will be posted by 
title and abstract on the Division Web site once specimens have been 
shipped. Note that

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biospecimens will be distributed blinded, that is, with an identifier 
that will only be linked to the study identification number upon 
completion of laboratory analyses, unless arrangements have been made 
for interim analyses beforehand.
    Progress Reports: Brief progress reports must be submitted annually 
to judge progress.
    Disposition of Results and Samples: No samples provided can be used 
for any purpose other than those specifically requested in the proposal 
and approved by the Technical Panel. No sample can be shared with 
others, including other investigators, unless specified in the proposal 
and so approved. Any unused samples must be either discarded or 
returned to the Division Repository, according to the wishes of the 
BRADSC upon completion of the approved project.
    Proposed Cost Schedule for Providing CPP Specimens: A nominal 
processing fee of approximately $8.00-$16.00 per sample, plus express 
shipping costs is anticipated for each sample requested and received. 
Costs will be fully estimated at the time of proposal acceptance and 
will take into consideration time and materials for the collection, 
storage and processing of the specimens by the Division Repository 
along with the preparation of the accompanying data files. The material 
costs are for the recurring laboratory costs to dispense and prepare 
the samples during collection and the computer software needed for the 
preparation of the data files. Because size of the shipments and 
distance to laboratories may vary, shipping costs will be estimated at 
the time of proposal acceptance. Cost reimbursement structures 
negotiated and accepted as part of a final proposal acceptance will be 
honored for one year from the date of proposal acceptance.
    Proposed Cost for Accessing CPP Microfiche Archives: There is no 
direct cost for accessing the CPP microfiche archives, although 
arrangements will have to be made for access to the building and is 
dependent upon the space available to accommodate a researcher.
    As additional specimens and resources from Division projects are 
made available for public use, announcements will be made on the 
Division Web site without further announcement in the Federal Register. 
As a reminder, the BRADSC and Division reserve the right to amend the 
proposal guidelines and cost schedule as needed and in keeping with the 
nature and complexity of the applicants' request.

    Dated: October 20, 2010.
Germaine M. Buck Louis,
Director and Senior Investigator, Division of Epidemiology, Statistics, 
and Prevention Research, Eunice Kennedy Shriver National Institute of 
Child Health and Human Development.
[FR Doc. 2010-27183 Filed 10-26-10; 8:45 am]
BILLING CODE 4140-01-P