[Federal Register: September 3, 2008 (Volume 73, Number 171)]
[Notices]               
[Page 51487-51489]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03se08-78]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

 
National Health and Nutrition Examination Survey (NHANES) Stored 
Biologic Specimens: Guidelines for Proposals To Use Samples and 
Proposed Cost Schedule

AGENCY: Centers for Disease Control and Prevention, Department of 
Health and Human Services.

ACTION: Notice and request for comments.

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SUMMARY: The National Health and Nutrition Examination Survey (NHANES) 
is a program of periodic surveys conducted by the National Center for 
Health Statistics (NCHS) of the Centers for Disease Control and 
Prevention (CDC). Examination surveys conducted since 1960 by NCHS, 
have provided national estimates of health and nutritional status of 
the United States civilian non-institutionalized population. To add to 
the large amount of information collected for the purpose of describing 
the health of the population in the most recent survey, serum, urine 
and limited plasma samples were collected and stored for future 
research projects. Specimens are currently available from NHANES III 
(conducted from 1988-1994) and from NHANES 1999+. In 1999, NHANES 
became a continuous survey with data release every two years. Specimens 
are available from two year survey cycles after the demographic file 
has been released to the public. Participants in the survey that began 
in 1999 signed a separate consent document agreeing to specimen storage 
allowing their biologic specimens to be used for approved research 
projects.
    Specimens are stored in two Specimen Banks. Surplus samples that 
were initially used for laboratory assays included in the surveys, have 
since been stored at -70[deg] C and have been through at least two 
freeze-thaw cycles. They are stored at a commercial repository under 
contract to NCHS. In addition, on average, six vials of sera were also 
stored in vapor-phase liquid nitrogen at the CDC and ATSTR Specimen 
Packaging, Inventory and Repository (CASPIR) Repository in 
Lawrenceville, GA. These specimens have not undergone a freeze-thaw 
cycle. The CASPIR Repository is considered a long-term repository for 
the NHANES specimens. NCHS is making both of these collections 
available for research proposals. The research proposals that can use 
the surplused specimens will receive higher priority. Proposals that 
request the specimens in CASPIR need to justify the use of the unthawed 
specimens.
    The purpose of this notice is to request comments on this program 
and the proposed cost schedule. After consideration of comments 
submitted, CDC will finalize and publish the cost schedule and accept 
proposals for use of the NHANES stored biologic samples. Please go to 
http://www.cdc.gov/nchs/about/major/nhanes/serum1b.htm for final 
proposal guidelines.
    All interested researchers are encouraged to submit proposals. No 
funding is provided as part of this solicitation. Samples will not be 
provided to those projects requiring funding until the project has 
received funds. Approved projects that do not obtain funding will be 
canceled. A more complete description of this program follows.

DATES: 
     Comment Receipt Date: October 3, 2008.
     Invitation to Submit Proposals: Can be submitted on an 
ongoing basis.
     Scientific Review Date: Within two months of proposal 
submission.
     Institutional Review Date: Within one month of final 
proposal acceptance.
     Anticipated distribution of samples: One month after IRB 
approval.

ADDRESSES: To send comments and to request information, contact: Dr. 
Geraldine McQuillan, Division of Health and Nutrition Examination 
Surveys, National Center for Health Statistics, Centers for Disease 
Control and Prevention, 3311 Toledo Road, Room 4204, Hyattsville, MD 
20782, Phone: 301-458-4371, Fax: 301-458-4028, E-mail gmm2@cdc.gov. 
Internet: http://www.cdc.gov/nchs/about/major/nhanes/serum1b.htm.

    Authority: Sections 301, 306 and 308 of the Public Health 
Service Act (42 U.S.C. 241, 242k and 242M).

SUPPLEMENTARY INFORMATION: The goals of NHANES are: (1) To estimate the 
number and percent of persons in the U.S. population and designated 
subgroups with selected diseases and risk factors; (2) to monitor 
trends in the prevalence, awareness, treatment and control of selected 
diseases; (3) to monitor trends in risk behaviors and environmental 
exposures; (4) to analyze risk factors for selected diseases; (5) to 
study the relationship between diet, nutrition and health; (6) to 
explore emerging public health issues and new technologies; and, (7) to 
establish and maintain a national probability sample

[[Page 51488]]

of baseline information on health and nutrition status.
    Specimens are available from the third National Health and 
Nutrition Examination Survey (NHANES III) and the continuous NHANES 
that started in 1999. Approximately 30,000 individuals were examined in 
NHANES III which began in the fall of 1988, and ended in the fall of 
1994. This survey can be analyzed in two phases. Phase 1 was conducted 
from October 1988 to October 1991 and Phase 2 began October 1991 and 
ended October 1994. Though participants consented to storing samples of 
their blood for future testing only research projects that include 
results that are judged not to have clinical significance for 
participants will be accepted. See: http://www.cdc.gov/nchs/about/
major/nhanes/nh3data.htm for more information on NHANES III.
    Beginning in 1999, NHANES became a continuous, annual survey with 
examination of approximately 5,000 individuals a year and data release 
every two years. Proposed research projects and samples requested must 
come from this two-year design (i.e. request must be for 1999-2000 
samples or 2001-2002, etc.). Samples from a single year of the survey 
will not be provided for research projects, but multiple two-year 
cycles may be requested. For details of the sampling design see the 
Analytic Guidelines at: http://www.cdc.gov/nchs/about/major/nhanes/
nhanes2003-2004/analytical_guidelines.htm.
    Starting in 1999 to 2008 survey participants were informed in the 
consent document for future laboratory analysis that they would not 
receive the results from these studies. Therefore, only research 
projects that propose laboratory results that do not have clinical 
relevance to an individual will be accepted by NCHS. Clinical 
significance of a laboratory test will be judged by the NHANES Medical 
Officer, but the researcher should address this in the research 
proposal. See http://www.cdc.gov/nchs/about/major/nhanes/nhanes2007-
2008/current_nhanes_07_08.htm for a copy of the current consent 
document.
    All proposals for use of NHANES samples will be evaluated by a 
technical panel for scientific merit and by the NHANES Ethics Review 
Board (ERB) for any potential human subjects concerns. The NHANES ERB 
will review the proposal even if the investigator has received approval 
by their institutional review panel.
    To determine if this limited resource should be used in the 
proposed projects, a Technical Panel will evaluate the public health 
significance and scientific merit of the proposed research. 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. See `Criteria for Technical Evaluation of Proposals' 
below. The proposal should outline how the results from the laboratory 
analysis will be used. Because NHANES is a complex, multistage 
probability sample of the national population, the appropriateness of 
the NHANES sample to address the goals of the proposal will be an 
important aspect of scientific merit. The survey oversamples the two 
largest race/ethnic minority groups, non-Hispanic blacks and Mexican 
Americans along with other subgroups of the population. Sampling 
weights are therefore used to make national estimates of frequencies. 
The use of weights, sampling frame and methods of assessment of 
variables included in the data are likely to affect the proposed 
research. The Technical Panel will review the analysis plan and 
evaluate whether the proposal is an appropriate use of the NHANES 
population. The Technical Panel will also assure that the proposed 
project does not go beyond either the general purpose for collecting 
the samples in the survey, or of the specific stated goals of the 
proposal.
    Investigators are encouraged to review the NHANES data, survey 
documents, manuals and questionnaires at: http://www.cdc.gov/nchs/
about/major/nhanes/nhanes99-02.htm or for NHANES III: http://
www.cdc.gov/nchs/about/major/nhanes/nh3data.htm.

Procedures for Proposals

    All investigators (including CDC investigators) must submit a 
proposal for use of NHANES specimens.
    Proposals are limited to a maximum of 10 single-spaced typed pages, 
excluding figures and tables, using 10 cpi type density. 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. All proposals 
should be E-mailed to gmm2@cdc.gov. 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. Proposals from CDC investigators 
must also include investigators scientific ethic verification number.
    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. NHANES is designed to 
provide prevalence estimates of diseases or conditions that are 
expected to affect between 5-10 percent of the population. Research 
proposals that expect much lower prevalence estimates need to provide 
more detail on why specimens from NHANES are needed for the project and 
provide details on how these data will be analyzed.
    (2) Background and Public Health Significance: Describe the public 
health significance, scientific merit and practical utility of the 
assay. Briefly describe in 1-2 pages the background of the proposal, 
identifying 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 proposal should justify the need for 
specimens that are representative of the U.S. population. The proposer 
should convey how the results will be used and the relationship of the 
results to the data already collected in NHANES. The proposer should 
include an analysis plan. The analyses ought to be consistent with the 
NHANES mission and the health status variables.
    (3) Research Design and Methods: Describe the research design and 
the procedures to be used. A detailed description of laboratory methods 
including validity and reliability must be included with references. 
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 sample size or a power calculation. 
If the researcher is requesting a sub-sample of specimens, a detailed 
description and justification, must be given. The researcher must 
describe how this sub-sample will be re-weighted to provide national 
estimates. The program will evaluate the study design and analysis plan 
in the proposal to determine whether the project is consistent with the 
design of the NHANES survey. Sub-samples are less useful to the 
research community when

[[Page 51489]]

the data are released in the public domain, so such requests will 
receive a lower priority for the specimens. Restricting a research 
proposal to demographic categories that are design variables for the 
survey is encouraged if laboratory testing must be restricted.
    (4) Clinical Significance or results: Since the consent document 
for specimen storage and continuing studies states that individual 
results will not 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 if many years have passed since the examination of the participant 
and collection of the sample. Any test with results that should be 
reported to a participant should be considered for inclusion in the 
concurrent survey, and is not appropriate for testing on the stored 
samples.
    (5) Qualification: Provide a brief description of the Principal 
Investigator's expertise in the proposed area should be provided, 
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 investigator should address his/her 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 NHANES 
Specimen Bank or discarded. The NCHS Project Officer must be consulted 
about the disposition of the samples.
    (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 cost per specimen is $6.50. The basis for the 
cost structure is in the last section of this document. Reimbursement 
for the samples will be collected before the samples are released.

Submission of Proposals

    Proposals can be submitted in MS Word format by E-mail to: Dr. 
Geraldine McQuillan, Division of Health and Nutrition Examination 
Surveys, National Center for Health Statistics, Centers for Disease 
Control and Prevention, 3311 Toledo Road, Room 4204, Hyattsville, MD 
20782, Phone: 301-458-4371 Fax: 301-458-4028, E-mail gmm2@cdc.gov.

Approved Proposals

    Approved projects will be provided specimens on receipt of a signed 
Materials Transfer Agreement (MTA) and a check (written to The Centers 
for Disease Control and Prevention) for the cost of the specimens. All 
laboratory results obtained from the samples will be sent back to NCHS 
to be linked to the sequence number that is the linking identifier on 
the public use files. All files will undergo disclosure review at NCHS. 
Within 90 days of the return of the data to NCHS these data may be 
released to the public.

Agency Agreement

    A formal signed agreement in the form of a Materials Transfer 
Agreement (MTA) with individuals who have projects approved will be 
completed before the release of the samples. This agreement will 
contain the conditions for use of the samples as stated in this 
document and as agreed upon by the investigators and CDC.

Progress Reports

    Brief progress report will be submitted annually. This will be the 
basis for the NHANES ERB continuation reports that are required 
annually.

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 and the NHANES ERB. No sample can be shared with others, 
including other investigators, unless specified in the proposal and so 
approved. Any unused samples must be returned to the NHANES Specimen 
Bank or disposed of upon completion of the approved project. These 
results, once returned to NCHS, will be part of the public domain. The 
proposer will have 90 days for quality control review of the data 
before public release.

Proposed Cost Schedule for Providing NHANES Specimens:

    A nominal processing fee of $6.50 is proposed for each sample 
received from the NHANES Specimen Bank. The costs include both the 
collection, storage and processing of the specimens along with the 
review of proposals and the preparation of the data files. These costs 
were based on an assumption that NCHS will receive and process eight 
proposals in a year, each requesting 5,000 samples as shown in the 
table below.
    The materials listed are for the recurring laboratory costs to 
dispense and prepare the samples during collection and for shipping; 
the computer software needed for the preparation of the data files and 
for the release of the data along with documentation on the NHANES Web 
page. Labor costs are based on a proposal administrator and computer 
programmers at NCHS to prepare the data files. The storage and pulling 
fees include the costs for the NHANES repository.

------------------------------------------------------------------------
                         Total costs                              Cost
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Labor........................................................      $0.70
Collection Storage...........................................       2.96
Pulling specimens............................................       1.04
Shipping.....................................................       0.31
Subtotal.....................................................       5.01
CDC/FMO support (10%)........................................       0.50
Subtotal.....................................................       5.51
NCHS support (18%)...........................................       0.99
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    Total....................................................       6.50
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    Comments are solicited on the proposed cost schedule. Comments are 
due by: October 3, 2008.
    Send Comments and Requests for Information to: Dr. Geraldine 
McQuillan, Division of Health and Nutrition Examination Surveys, 
National Center for Health Statistics, Centers for Disease Control and 
Prevention, 3311 Toledo Road, Room 4204, Hyattsville, MD 20782, Phone: 
301-458-4371; Fax: 301-458-4028, e-mail gmm2@cdc.gov.

    Dated: August 26, 2008.
James D. Seligman,
Chief Information Officer, Centers for Disease Control and Prevention.
[FR Doc. E8-20335 Filed 9-2-08; 8:45 am]

BILLING CODE 4163-18-P