[Federal Register Volume 75, Number 108 (Monday, June 7, 2010)]
[Notices]
[Pages 32191-32195]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-13517]



[[Page 32191]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention


National Health and Nutrition Examination Survey (NHANES) DNA 
Samples: Guidelines for Proposals To Use Samples and Cost Schedule

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

ACTION: Notice.

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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 the health and nutritional status of the 
U.S. civilian non-institutionalized population. To add to the extensive 
amount of information collected for the purpose of describing the 
health of the population, DNA specimens were collected during three 
NHANES surveys. DNA is available in the form of crude lysates of cell 
lines derived from 7,159 participants enrolled in Phase II of NHANES 
III (1991-1994). In addition, DNA purified from whole blood is also 
available from 7,839 participants enrolled in the NHANES 1999-2002 and 
4,615 participants enrolled in NHANES 2007-2008. All specimens (NHANES 
III, NHANES 1999-2002 and NHANES 2007-2008) were sent to the Division 
of Laboratory Sciences (DLS) at the National Center for Environmental 
Health (NCEH) for processing. DNA samples from these specimens are 
being made available to the research community for genetic analyses.
    No funding is provided as part of this solicitation. NCHS will 
review proposals twice a year, in January and July. Proposals will be 
reviewed by a technical panel and by an internal Secondary Review 
Committee of senior CDC scientists. The Secondary Review Committee will 
perform a programmatic review based on the results of the technical 
review panel and consider the scientific and technical results from the 
first level of review, important programmatic considerations such as 
program priorities, program relevance, and other criteria germane to 
this announcement and to CDC. Projects approved by both reviews will be 
submitted to the NCHS Ethics Review Board for final approval.
    Approved projects that do not obtain funding on their own will be 
canceled. A more complete description of this program follows.

DATES: 
     Submission of Proposals: On January 1 and July 1 of each 
year.
     Scientific Review: 30 days after proposal submission date.
     Secondary Review: Approximately 30 days after Scientific 
review is complete.
     Ethics Review Board: Approximately 30 days after Secondary 
review is complete.
     Notification of approval: Approximately 30 days after ERB 
approval.
     Anticipated distribution of samples: Approximately 60 days 
after all approvals are obtained.

    Note:  Timeframe may vary depending on the nature of the 
proposal and the results of each level of review. Unforeseen 
circumstances could result in a change to this schedule.


ADDRESSES: To send comments and for information, contact: Geraldine 
McQuillan, PhD, 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].

    Authority:  Sections 301, 306 and 308 of the Public Health 
Service Act (42 U.S.C. 241, 2421 and 242m).


SUPPLEMENTARY INFORMATION: The goals of NHANES are (1) To estimate the 
number and percentage of people in the U.S. population and designated 
subgroups with selected diseases and risk factors for those diseases; 
(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 relation among diet, nutrition and health; 
(6) to explore emerging public health issues and new technologies; (7) 
to establish and maintain a national probability sample of baseline 
information on health and nutritional status.
    The availability of the NHANES III DNA samples has been previously 
announced (Thursday, August 8, 2002 [67 FR 51585], Friday, January 13, 
2006 [71 FR 22248]), Thursday, October 18, 2007 [72 FR 59094] and 
Thursday, September 3, 2009 [(74 FR 45644)]. NHANES III DNA samples are 
in the form of crude cell lysates available from the cell lines derived 
from samples obtained from Phase II (1991-1994) participants. DNA 
concentrations are unknown and vary between samples (see NHANES III DNA 
Samples section for a description).
    Beginning in 1999, NHANES became a continuous, annual survey rather 
than a periodic survey. For a variety of reasons, including disclosure 
and reliability issues, the survey data are released on public use data 
files every two years. In addition to the analysis of data from any two 
year cycle, it is possible to combine two cycles to increase sample 
size and analytic options. Blood samples for DNA purification were 
collected from participants age 20 or more years in survey years 1999-
2002 and 2007-2008. Purified DNA samples are available from these 
survey years in a single set from each survey cycle. DNA samples can be 
obtained and analyzed with survey data from the NHANES 1999-2000 or 
2001-2002 or all four years combined (NHANES 1999-2002) and NHANES 
2007-2008. The data release cycle for the NHANES during the period in 
which DNA specimens were collected is described as NHANES 1999-2000, 
NHANES 2001-2002 and NHANES 2007-2008.
    See: http://www.cdc.gov/nchs/nhanes/nhanes99_00.htm, http://www.cdc.gov/nchs/nhanes/nhanes01-02.htm, http://www.cdc.gov/nchs/nhanes/nhanes2007-2008/nhanes07_08.htm for additional details.
    Identifiable health information collected in the NHANES is kept in 
strictest confidence. During the informed consent process, survey 
participants are assured that data collected will be used only for 
stated purposes and will not be disclosed or released to others without 
the consent of the individual in accordance with section 308(d) of the 
Public Health Service Act (42 U.S.C. 242m). In NHANES 1999-2002 and 
2007-2008, a separate consent form was signed by eligible participants 
who agreed to the storing of specimens for future genetic research. 
Only participants that consented specifically to future genetic 
research in 1999-2002 and 2007-2008 will be available for analyses. 
Genetic variation results will be linked to the requested information 
from the NHANES public use data file by the Division of Health and 
Nutrition Examination Surveys (DHANES) staff. All analyses must be done 
through an NCHS Research Data Center (RDC) approved mechanism to assure 
confidentiality.

Research Proposals Categories

    Note that the following proposal categories differ from those used 
in

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previous announcements for use of NHANES III DNA samples (Thursday, 
August 8, 2002 [67 FR 51585] and Friday, January 13, 2006 [71 FR 
22248].
    Category (A): Studies involving the typing of the complete set of 
NHANES DNA samples (NHANES III, 7,159 samples; NHANES 1999-2002, 7,839 
samples; NHANES 2007-2008, 4,615 samples) for proposals that 
investigate specific research hypotheses that relate tests of selected 
genes and demographic or demographic and phenotypic data available from 
NHANES. This category is open for proposals for use of NHANES III, 
NHANES 1999-2002 and NHANES 2007-2008 samples. A total of ten full sets 
of samples for each survey will be available for any review cycle. The 
investigator will specify which DNA bank, NHANES III, NHANES 1999-2002 
or 2007-2008, they are requesting as well as the genetic analyses to be 
conducted on the samples. The investigator will also include in the 
research protocol an analytic plan that includes a list of NHANES 
demographic and clinical variables that would be used for the data 
analyses. The researcher will conduct the genetic analyses of the 
approved variations on the samples that are labeled with a unique 
identification number that is not directly linkable to the public use 
file and therefore, anonymous to the researcher. To analyze these data 
with the NHANES public use data, the researcher will provide the 
genetic variation results with the identification numbers to the 
Division of Health and Nutrition Examination Surveys. The 
identification numbers will be matched to the requested variables from 
public use files data by DHANES staff for analyses that must be 
conducted through the NCHS RDC or its equivalent. Proposals are limited 
to the testing of 1,000 genetic variations or less. NCHS cannot 
guarantee that frequencies for all genetic variations can be published 
due to confidentiality concerns.
    After the NCHS has completed the initial quality control 
assessment, researchers will be given up to six months to conduct a 
more comprehensive quality assurance review. The timeframe allowed for 
this review will depend on the number and characteristics of the 
genetic tests submitted. At the completion of this review, an 
announcement will be made to the public announcing the availability of 
the genetic variation results and the opportunity to link these results 
to other NHANES data for secondary data analysis. The list of currently 
available SNPs is available at: http://www.cdc.gov/nchs/nhanes/genetics/genetic_types.htm.
    All samples will be distributed in complete sets of samples of 96 
well plates. NHANES III DNA is in the form of crude cell lysates. There 
will be a total of 7,159 NHANES III samples distributed in a total of 
75 plates with an additional four plates of quality control samples. 
There are 7,839 NHANES 1999-2002 purified DNA samples. These will be 
distributed into 82 plates with approximately five plates of quality 
control samples. There are 4,615 purified DNA samples available from 
NHANES 2007-2008. These will be distributed into 49 plates with 
approximately three plates of quality control samples.

    Note:  If the investigator would like to propose a subsample of 
the full set please contact the Program to discuss feasibility.

    Category (B): Additional research using samples already obtained 
from previous solicitations: Researchers that have obtained NHANES DNA 
samples from previous solicitations and have sufficient DNA left may 
request to do additional tests on the remaining DNA. Proposals under 
this Category must be submitted and approved before the DNA samples 
were scheduled to be destroyed or returned. The investigator will 
specify the genetic analyses to be conducted on the samples. The 
investigator will also include in the research protocol an analytic 
plan that includes a list of demographic and clinical variables that 
would be used for the data analyses.
    Category (C) Proposals involving whole-genome genotyping of DNA 
samples: All proposals for whole-genome genotyping of more than 1,000 
genetic variations must provide funding for the testing to the NHANES 
program so that the testing can be done under an NHANES contract. If 
funding is available, CDC intends to provide whole genome-genotyping 
data from NHANES III and NHANES 1999-2002 samples. These data will be 
available for secondary data analysis.

NHANES III DNA Samples

    The laboratory will distribute aliquots of crude cell lysates. DNA 
concentrations vary and are estimated to range from 7.5-65 ng/[mu]L 
with an average of approximately four micrograms in 100 [mu]L. Each 96 
well plate will be bar-coded and labeled with a readable identifier. 
Quality control samples (approximately 384 samples) will be sent at no 
charge, either inserted with the NHANES samples or in separate plates, 
as blind replicates and/or blanks. Description of these samples and 
cost has been previously published see: (Friday, January 13, 2006 [71 
FR 22248]).

NHANES 1999-2002 and 2007-2008 DNA Samples

    The laboratory will distribute aliquots of purified DNA of 
normalized concentrations of 50 ng/[mu]L whenever possible. Some 
samples may fall below this threshold. Forty microliters of each 
specimen will be supplied. The amount of DNA in each aliquot may vary 
but will be on average approximately two micrograms. Each 96 well plate 
will be bar-coded and labeled with a readable identifier. Quality 
control samples (NHANES 1999-2002, approximately 480 samples; NHANES 
2007-2008, approximately 288 samples) will be sent at no charge, either 
inserted with the NHANES samples or in separate plates, as blind 
replicates and/or blanks.

Proposed Cost Schedule for Providing NHANES DNA Samples

    Costs are determined both for NCEH and NCHS and include the 
physical materials needed to process the samples at the NCEH 
laboratory, as well as the materials to process the requests for 
samples at NCHS. These costs include salaries of the staff needed to 
conduct these activities at each Center. The fee is estimated to cover 
the costs of processing, handling, and preparing the samples. Technical 
panel travel and expenses are based on the panel meeting twice a year. 
The space estimate is based on acquiring storage and sample aliquoting 
space in the laboratory. The cost per samples for NHANES III samples is 
the same as published in 2006 (Friday, January 13, 2006 [71 FR 22248]) 
and the cost for NHANES 1999-2002 and NHANES 2007-2008 are the same as 
published in 2007 (Thursday, October 18, 2007 [72 FR 5904]).

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                                                          Cost per sample                       Cost per sample
                                       Cost per sample    partial set, 99-   Cost per sample      partial set,
             Total costs              full set, 99-02 &      02 & 07-08      full set, NHANES      NHANES III
                                            07-08        (special request)         III         (special request)
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Materials...........................              $0.89              $2.19              $0.85              $1.90
Labor...............................               4.60              25.30               3.30              22.00
Application review and other                       0.54               3.09               0.35               2.69
 administrative expenses............
Space...............................               0.17               1.12               0.13               0.97
                                     ---------------------------------------------------------------------------
    Subtotal........................               6.20              31.70               4.63              27.56
NCHS overhead (18 percent)..........               1.12               5.71               0.83               4.97
                                     ---------------------------------------------------------------------------
    Subtotal........................               7.32              37.41               5.46              32.52
CDC/FMO overhead (0.9 percent)......               0.66               3.37               0.49               2.93
                                     ---------------------------------------------------------------------------
    Total sample cost per sample....               7.98              40.78               5.95              35.45
                                     ===========================================================================
    Total cost per proposal.........     99-02: $63,555                 NA          42,596.36                 NA
                                         07-08: $36,828
                                     ===========================================================================
    Total cost per Category B             99-02: $6,255                \1\              4,260                \1\
     proposal: for data handling....      07-08: $3,683
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\1\ 10 percent of original cost of samples.

Procedures for Proposals

    The investigator should follow these instructions for preparation 
of proposals. Once testing is complete the IRB protocol is closed and 
the project is transferred to the Research Data Center (RDC). The 
content of the IRB protocol becomes the RDC project description and the 
project is covered by the umbrella RDC IRB Protocol. Protocols must be 
written using the outline below. All proposal categories need a full 
research proposal for review. In addition to the cover page, the 
research proposal should contain the title of the research project, the 
name, address phone number and E-mail address of the lead investigator 
along with the name of the institution where the genotyping will be 
conducted, and the category of proposal (A, B or C) submitted. Office 
of Human Research Protections assurance numbers for the institutions 
engaged in the research project should be included. CDC investigators 
need to include their Scientific Ethics Verification Number. E-mail 
submission of the proposal is encouraged.
    The proposals should be a maximum of 20 single-spaced typed pages, 
excluding figures and tables, using ten cpi type density. Please use 
appendices sparingly. If a proposal is approved, the title, specific 
aims, name, and phone number of the author will be maintained by NCHS 
and released if requested by the public. Unapproved proposals will be 
returned to the investigator and will not be maintained by NCHS.
    Since the number of sets of DNA is limited, proposals will be 
reviewed by the technical panel and then will be reviewed by a 
secondary review panel composed of CDC officials. The technical panel 
will determine if the proposal is technically sound and if so, the 
technical panel will rank the proposal on a scale of 0-100. Proposals 
that are rejected will not be scored.
    Applications will also be reviewed by an internal Secondary Review 
Committee which will perform a programmatic review based on the results 
of the peer review for technical merit. The Secondary Review Committee 
considers the scientific and technical merit results from the first 
level of review, important programmatic considerations such as program 
priorities, program relevance, and other criteria germane to this 
announcement and to CDC. The Secondary Review Panel will be comprised 
of senior CDC scientists. Approved proposal will then be reviewed by 
the CDC/NCHS Ethics Review Board (ERB) to ensure appropriate human 
subjects protections are provided, in compliance with 45 CFR 46.
    Category A, B and C Proposals should include the following 
information:
    (1) Cover sheet: See Example in Sample Proposal on http://www.cdc.gov/rdc/B3Prosal/PP320.htm Also include, the name of the 
institution where the genotyping will be conducted, which category, and 
Office of Human Research Protections assurance numbers for the 
institutions engaged in the research project should be included. Plus, 
CDC investigators need to include their Scientific Ethics Verification 
Number.
    (2) Abstract: Please limit the abstract to 300 words.
    (3) 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.
    (4) Background and Public Health Significance: (A) Describe the 
public health significance of the proposed research. (B) Discuss how 
the results will be used. Analyses should be consistent with the NHANES 
mission to assess the health of the nation. The Panel will ensure that 
the proposed project does not go beyond either the general purpose for 
collecting the samples in the survey or the specific stated goals of 
the proposal.
    (5) Design, Method, and Output: (A) Research Design and Methods: 
Describe the analytic and statistical methods to be employed. Include 
power calculations. For all proposal categories, include a detailed 
description of the laboratory methods. The characteristics of the 
laboratory assay, such as reliability, validity, should be included 
with appropriate references. The potential difficulties and limitations 
of the proposed procedures should also be discussed. Address adequate 
methods planned for handling and storage of samples. (1) Category A 
proposals will be provided with approximately 480 quality control 
samples at no additional cost. Approved projects must run these quality 
control samples and submit the results from the NHANES DNA samples. (2) 
Category B proposals will be required to use residual quality control 
samples. The proposal should contain a discussion of additional quality 
control procedures the laboratory will use to assure the validity of 
the test results. Address adequate methods planned for handling and 
storage of samples. (B). Output: Please describe any output that you 
would like to take out of the RDC: Please be detailed as this section 
helps

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the Review Committee assess disclosure risk. Include detailed examples 
of table shells, models, and/or graphs. How will you present the 
results of this project? (C). Data Dictionary: Includes (1) NCHS 
Restricted Data Dictionary (2) NCHS Public Use Data Dictionary (3) Non-
NCHS Data Dictionary see: http://www.cdc.gov/rdc/B3Prosal/PP323.htm. 
The appropriateness and adequacy of the methodology proposed to reach 
the research aims as well as the appropriateness of using the NHANES a 
complex, multistage probability sample of the national population, to 
address the goals of the proposal will be assessed.
    (6) Additional information for NHANES: (A) Discussion Regarding the 
Race/Ethnicity Variables: If the research is limited to specific race 
or ethnic groups (only applicable for a subsample request) or if 
information about the race or ethnicity of the subjects is requested, 
indicate the reason for analyzing race/ethnicity and how the results 
will be interpreted. Discuss the potential for group harm. (B) Clinical 
Relevance of Research Findings: The samples under this Plan are 
available for genetic research, not genetic testing. Therefore, it is 
the intent of the program to approve only those proposals that would 
yield meaningful research, but not clinically relevant information for 
the participants. Researchers should justify that the test results 
should not be reported to the subjects. (C) Period of Performance: 
Specify the project period. The period may be up to three years. At the 
end of the project period, any unused samples must be returned to the 
NHANES DNA Specimen Bank in accordance with instructions from the 
Division of Environmental Laboratory Science. Extensions to the period 
of performance may be requested. (D) Funding: Include the source and 
status of the funding to perform the requested laboratory analysis. 
Investigators will be responsible for the cost of processing and 
shipping the samples (See table). Also, in general information for RDC.
    (7) References
    (8) R[eacute]sum[eacute]s/CV: Please include a 2-page CV for each 
member of the research team in this document (not as attachments).

Public Availability of Data

    Genetic test results from all studies using NHANES DNA samples will 
be made available to the public for secondary data analyses. After the 
NCHS quality control review is completed, researchers will be given up 
to six months to conduct a more comprehensive quality assurance review. 
The final quality control review timeframe will be negotiated between 
the researcher and the NCHS Project Officer and will depend on the 
number and characteristics of the genetic tests submitted. This time 
for final review is provided before the announcement is made to the 
public that the test results are available for submission of proposals 
for secondary data analyses. The list of currently available genotypes 
will be outlined on: http://www.cdc.gov/nchs/nhanes/genetics/genetic_types.htm. Proposals for secondary data analyses linking NHANES public 
use data with genetic variation data will be reviewed by the Research 
Data Center on a rolling basis see: http://www.cdc.gov/rdc/B3Prosal/PP320.htm for proposal guidelines.

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

    In NHANES III, NHANES 1999-2002, and NHANES 2007-2008 race/
ethnicity was derived by combining responses to questions on race and 
Hispanic origin. For NHANES III, These categories are defined as non-
Hispanic white, non-Hispanic black, or Mexican American. For NHANES 
1999-2002, and NHANES 2007-2008, these categories are defined as non-
Hispanic white, non-Hispanic black, Mexican American or Other 
Hispanics. Individuals who did not self-select into these categories 
were classified as ``other''. If proposal requests a subsample and 
excludes one or more race/ethnic groups or a gender, this exclusion 
must be justified.
    CDC is also sensitive to the stigmatization of racial/ethnic 
specific populations through inappropriate reporting and interpretation 
of findings. For all proposals that request information on race/
ethnicity for the samples selected, the investigator should discuss the 
reason for analyzing race/ethnicity, how the results will be 
interpreted, and the potential for group harm.

Submission of Proposals

    Proposals can be submitted immediately. The review process will 
begin approximately 60 days from the publication of the notice and will 
include all proposals submitted as of that date.
    Electronic submission of proposals is encouraged. Please submit 
proposals to: Geraldine McQuillan, PhD, 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: 301-458-4840, Fax: 301-458-4028 E-
Mail: [email protected].

Approved Proposals

    The genetic results will be sent back to NCHS so they can be linked 
to the requested NHANES III, NHANES 1999-2002 or NHANES 2007-2008 
public use data. Analysis will be done in the Research Data Center.

Agency Agreement

    A formal signed agreement in the form of a Materials Transfer 
Agreement (MTA) with individuals who have projects approved and funding 
has been secured will be completed before the release of the samples. 
This agreement will contain the conditions for use of the DNA as stated 
in this document and as agreed upon by the investigators and CDC. A key 
component of this agreement is that no attempt will be made to link the 
results of the proposed research to any other data, including, but not 
limited to, the NHANES public use data sets outside the Research Data 
Center. Also, the investigator agrees that the samples cannot be used 
for commercial purposes. A list of genes generated from the testing of 
the NHANES samples will be made available to the public for potential 
solicitation of proposals for secondary data analysis after the quality 
control process has been completed (approximately six months after NCHS 
receives the genetic variation results). These secondary data analysis 
proposals must also be reviewed by the ERB.

Progress Reports

    A progress report will be submitted annually. CDC/NCHS/ERB 
continuation reports are also required annually if testing is not 
completed within a year. An ERB continuation form will be sent to the 
researcher each year for project update.

Termination of ERB Protocol

    At the end of laboratory testing the Ethics Review Board Protocol 
will be closed. All data analysis will be conducted through the NCHS 
Research Data Center (RDC). For secondary data analysis project an 
analytic plan must be submitted to the RDC to set up the analytic data 
set. See: http://www.cdc.gov/nchs/r&d/rdc.htm for guidelines.

Disposition of Results and Samples

    No DNA samples provided can be used for any purpose other than 
those specifically requested in the proposal and approved by the 
Genetics Technical Panel, the Secondary Review Committee and the NHANES 
ERB. No sample can be shared with others, including other 
investigators, unless specified in the proposal and so approved. Any 
unused

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samples must be returned upon completion of the approved project. These 
results, once returned to NCHS and quality controlled, will be part of 
the public domain. Genetic test results from all studies using NHANES 
DNA samples will be made available to the public for secondary data 
analyses. After the NCHS quality control review is completed, 
researchers will be given up to six months to conduct a more 
comprehensive quality assurance review. The final quality control 
review timeframe will be negotiated between the researcher and the NCHS 
Project Officer and will depend on the number and characteristics of 
the genetic tests submitted. Data analyses will be conducted at the 
NCHS' Research Data Center or similar environment provided by NCHS. 
Proposals for secondary data analyses are accepted on a rolling basis 
(http://www.cdc.gov/nchs/nhanes/genetics/genetic_types.htm).

Send Requests for Information

    Geraldine McQuillan, PhD, 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 24, 2010.
Tanja Popovic,
Deputy Associate Director for Science, Centers for Disease Control and 
Prevention.
[FR Doc. 2010-13517 Filed 6-4-10; 8:45 am]
BILLING CODE 4163-18-P