[Federal Register Volume 69, Number 100 (Monday, May 24, 2004)]
[Notices]
[Pages 29551-29554]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-11635]


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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

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 and urine 
were collected and stored for future research projects.

[[Page 29552]]

Specimens are currently available from NHANES III (conducted from 1988-
1994) and from NHANES 1999-2002. Participants in the survey that began 
in 1999 signed a separate consent document agreeing to this storage, 
and 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 McKesson BioServices Repository 
in Rockville, MD. In addition, on average, six vials of sera were also 
stored in vapor-phase liquid nitrogen at the CDC 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: June 23, 2004.
     Invitation To Submit Proposals: July 23, 2004 or can be 
received at any time.
     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.
    To Send Comments and To Request Information: 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, 
telephone: 301-458-4371, fax: 301-458-4028, e-mail [email protected]. 
Internet: http://www.cdc.gov/nchs/about/major/nhanes/serum1b.htm.

SUPPLEMENTARY INFORMATION: The goals of NHANES are: to estimate the 
number and percent of persons in the U.S. population and designated 
subgroups with selected diseases and risk factors; to monitor trends in 
the prevalence, awareness, treatment and control of selected diseases; 
to monitor trends in risk behaviors and environmental exposures; to 
analyze risk factors for selected diseases; to study the relationship 
between diet, nutrition and health; to explore emerging public health 
issues and new technologies; and, to establish and maintain a national 
probability sample of baseline information on health and nutrition 
status.
    Specimens are available from NHANES III, which was conducted from 
1988-1994 and the current cycle of NHANES where data has been released 
(1999-2002). In the future, specimens will be available for a two-year 
cycle of NHANES after the public release of the collected data. The 
current National Health and Nutrition Examination Survey (NHANES) began 
in April 1999 and is a continuous yearly study. Data are released on a 
two-year cycle, and 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 (i.e. four years) may be requested but should be justified. For 
details of the sampling design see the Analytic Guidelines at: http://www.cdc.gov/nchs/about/major/nhanes/NHANES99_00.htm.
    The third National Health and Nutrition Examination Survey (NHANES 
III) began in the fall of 1988, and ended in the fall of 1994. The 
survey can be analyzed in two phases. Phase 1 was conducted from 
October 1988 to October 1991. Phase 2 began October 1991 and ended 
October 1994. Approximately 30,000 individuals were examined during the 
six years of the survey with 15,000 in each three-year sample. See: 
http://www.cdc.gov/nchs/about/major/nhanes/datalink.htm#NHANESIII for 
more information on NHANES III.
    Survey participants in the current NHANES which began in 1999, who 
signed the consent document for future research, were informed 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/data/nhanes/00futstu.pdf for a 
copy of the consent document. Though storage of blood specimens for 
future research was mentioned in the NHANES III consent document, a 
separate consent for use of these specimens was not obtained. The 
NHANES Ethics Review Board (ERB) has accepted the language in the 
NHANES III consent document to cover the use of the specimens, but only 
research projects that include results that are judged not to have 
clinical significance for participants will be accepted.
    All proposals for use of NHANES samples will be evaluated by a 
technical panel for scientific merit and by the NHANES 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.
    The 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 Technical Panel will 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.
    NHANES is a representative sample of the U.S. population. The 
survey oversamples the two largest race/ethnic minority groups, non-
Hispanic blacks and Mexican Americans along with other subgroups of the 
population.

[[Page 29553]]

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. Since data from NHANES 99+ is released in two-year cycles, 
proposals will only be accepted for use of specimens from the two years 
of a release cycle. Multiple two-year cycles may be requested but the 
need for the additional sample size should be justified. Proposals for 
NHANES III can request specimens from one or both phases of the survey.

Procedures for Proposals

    All investigators (including CDC investigators) must submit a 
proposal for use of NHANES specimens.
    Proposals are limited to a maximum of ten single-spaced typed 
pages, excluding figures and tables, using ten 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 [email protected].
    The Criteria for Technical Evaluation of Proposals section at the 
end of this announcement and the following information should be used 
to develop the proposal content.
    Research proposals that can use the NHANES III specimens, which has 
a large number of available samples but come from an earlier time 
period, will receive priority.
    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--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. Studies that do not need a national sample or request 
a subset of samples such that estimates cannot be weighted to make 
national estimates will not be accepted.
    3. 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. 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.
    4. Research Design and Methods--Describe the research design and 
the procedures to be used. A detailed description of laboratory methods 
must be included with references. Laboratory quality control should be 
described. 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 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.
    5. Qualification of Investigators--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. Funding--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. At 
this time the cost per specimen is $2.00. 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.
    7. Timeline for laboratory tests--NHANES ERB approval of the 
individual research projects must be renewed every year. Investigators 
must have substantial progress (defined by the start of laboratory 
testing) in the first year, and all testing should be completed in the 
second year. 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.

Requirements for the Inclusion of Women and Racial and Ethnic 
Minorities in Research

    The following policy must be followed in the submitted proposals:
    It is the policy of the CDC and the Agency for Toxic Substances and 
Disease Registry (ATSDR) to ensure that individuals of both sexes and 
the various racial and ethnic groups will be included in the CDC/
ATSDR--supported research projects involving human subjects, whenever 
feasible and appropriate. Racial and ethnic groups are those defined in 
the OMB Directive No, 15 and include American Indian or Alaska Native, 
Asian, Black or African American, Hispanic or Latino, Native Hawaiian 
or Other Pacific Islander. Applicants shall ensure that women and 
racial ethnic minority populations are appropriately represented in 
applications for research involving human subjects. When clear and 
compelling rationale exists that inclusion is inappropriate or not 
feasible, this situation must be explained as part of the application. 
This policy does not apply to research studies when the investigator 
cannot control the race, ethnicity and/or sex of subjects. Further 
guidance to this policy is contained in the Federal Register, Vol. 60, 
No. 179, pages 47947-47951, and dated Friday, September 15, 1995.

Submission of Proposals

    Investigators are invited to submit proposals 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, telephone: 301-458-4371, fax: 301-458-4028, e-
mail [email protected].

[[Page 29554]]

Criteria for Technical Evaluation of Proposals

    The following criteria will be used for technical evaluation of 
proposals:
    1. Background and Public Health Significance: The public health 
significance, scientific merit and practical utility of the assay. 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.
    2. Research Design and Methods: The sampling scheme or age/race-
ethnic/ gender categories for the testing must be described and 
addressed with regards to its relationship to the NHANES design. Power 
calculations for a sub-sample must be included (see Procedures for 
Proposals for evaluation of proposals that suggest use of sub-samples). 
A list of variables that will be used in the initial data analyses 
should be included to demonstrate familiarity by the proposer with the 
dataset.
    A detailed description of the laboratory methods should be 
included. The characteristics of the laboratory assay, such as 
reliability, validity, and ``state-of-the-art'', must be included with 
appropriate references. The potential difficulties and limitations of 
the proposed procedures should be discussed. The volume of specimen and 
the number of samples required should be specified. Adequate methods 
for handling and storage of samples must also be addressed. The 
laboratory must demonstrate expertise in the proposed laboratory test 
and the capability for handling the workload requested in the proposal.
    3. Clinical Significance or results: Since the current 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. Any test with 
results that should be reported to a participant should be considered 
for inclusion in the concurrent survey, and are not appropriate for 
testing on the stored samples.
    4. Discussion regarding the race/ethnicity variables: If all race/
ethnic groups are not requested, the proposal gives a clear and 
compelling rationale for not including them.
    5. Qualifications: A brief description of the requestor's expertise 
in the proposed area must 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--The project period should be specified. 
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. 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.

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. Within six months 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 also 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 Bank or disposed 
of upon completion of the approved project.
    These results, once returned to NCHS, will be part of the public 
domain. The data will not be released until approximately six months 
after reporting the results to NCHS, to allow the investigator time to 
publish results, unless otherwise required by Federal law.

Proposed Cost Schedule for Providing NHANES III DNA Specimen Bank

    A nominal processing fee of $2.00 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 four 
proposals in a year, each requesting 5000 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 fee is the 
cost of storage at the NHANES repository.

------------------------------------------------------------------------
                                                                Cost per
                         Total costs                              vial
------------------------------------------------------------------------
Labor........................................................      $0.30
Storage......................................................       0.28
Pulling specimens............................................       0.68
Shipping.....................................................       0.20
Subtotal.....................................................       1.46
NCHS overhead (15%)..........................................       0.22
Subtotal.....................................................       1.68
CDC/FMO overhead (20%).......................................       0.34
                                                              ----------
    Total....................................................       2.00
------------------------------------------------------------------------

    Comments are solicited on the proposed cost schedule. Comments are 
due by: June 23, 2004.
    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 [email protected].

    Dated: May 12, 2004.
James D. Seligman,
Associate Director for Program Services, Centers for Disease Control 
and Prevention.
[FR Doc. 04-11635 Filed 5-21-04; 8:45 am]
BILLING CODE 4163-18-P