[Federal Register Volume 74, Number 170 (Thursday, September 3, 2009)]
[Notices]
[Pages 45644-45648]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-21287]



[[Page 45644]]

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

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 approximately 7,157 participants enrolled in Phase 
II of NHANES III (1991-1994). In addition, DNA purified from whole 
blood is also available from approximately 7,900 participants enrolled 
in the NHANES 1999-2002 and 4,621 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 beginning in January and July of each 
year. 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].

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]) and Thursday, October 18, 2007 [72 FR59094]. 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. 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 or 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 previous announcements for use of 
NHANES III DNA samples (Thursday, August 8,

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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, 7,157 samples; NHANES 1999-2002, 
approximately 7,900 samples; NHANES 2007-2008 4,621 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 the publication of frequencies for all 
genetic variations 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/nh3data_genetic.htm#Available_Genetic_Data_Sets.
    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 7,157 NHANES III samples distributed in a total of 
75 plates with an additional five plates of quality control samples. 
There are approximately 7,900 NHANES 1999-2002 purified DNA samples. 
These will be distributed into 83 plates with approximately five plates 
of quality control samples. There are 4,421 purified DNA samples 
available from NHANES 2007-2008. These will be distributed into 51 
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 480 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, 99-02   Cost per sample,      partial set,
           Total costs             full set, 99-02 &   & 07-08 (special    full set,  NHANES      NHANES III
                                         07-08             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.........              63,024                  NA           42,596.36                  NA
                                 ===============================================================================
Total Cost per Category B                      6,302               (\1\)               4,260               (\1\)
 Proposal: for Data handling....
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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. Both proposal categories 
need a full research proposal for review. The cover page of 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 DNA analysis will be 
done, 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. The technical panel will evaluate 
the whole proposal but will focus on proposal elements 1, 3, and 4.
    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.
    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 
proposed research. Scientific merit will be judged on the basis of 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. Convey how the 
results will be used and the relationship of the results to the data 
already collected in NHANES 1999-2002. Analyses should be consistent 
with the NHANES mission to assess the health of the nation. Because 
NHANES is a complex, multistage probability sample of the national 
population, the appropriateness of using the NHANES sample to address 
the goals of the proposal will be an important aspect of determining 
scientific merit. The Panel will ensure that the proposed project does 
not go beyond either the general purpose for collecting the samples in 
the survey, i.e., to determine allele frequencies in subgroups of the 
population, or, the specific stated goals of the proposal.
    (3) Research Design and Methods: Include power calculations and a 
list of variables requested. 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. 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. 
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.
    (4) 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.
    (5) Clinical Relevance of Research Findings: The samples for 
research based on specific hypothesis 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

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results should not be reported to the subjects.
    (6) Qualifications: Provide a brief description of the requestor's 
expertise in the proposed area, including publications in this area 
within the last three years.
    (7) 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.
    (8) 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. 
Currently the cost per DNA specimen is $7.98 for NHANES 1999-2002 and 
2007-2008 proposals that use the full set of samples. Costs for partial 
sets are $40.78 per specimen. Reimbursement for the samples will be 
collected before the samples are released. NHANES III samples which are 
DNA crude lysates, not purified DNA, are $5.95 per sample for the 7,157 
total set of samples. If a subsample of NHANES III is requested and 
approved the cost schedule published in (Friday, January 13, 2006 [71 
FR 22248]) will be utilized ($35.45 per sample).
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/nh3data_genetic.htm#Available_Genetic_Data_Sets.
    Proposals for secondary data analyses linking NHANES public use 
data with genetic variation data are accepted in May and October of 
each year.
    Proposals to obtain DNA for testing will be reviewed first by a 
Genetics Technical Panel and then by a Secondary Review Panel. 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 part 46. The ERB review will be conducted, even 
though investigators' proposals may have received review by their home 
institution. The Director of NCHS will verify that projects have 
received appropriate reviews.
    Requirements for the Inclusion of Women and Racial and Ethnic 
Minorities in Research: In NHANES III and NHANES 1999-2002, race/
ethnicity was derived by combining responses to questions on race and 
Hispanic origin. These categories are defined as non-Hispanic white, 
non-Hispanic black, or Mexican American. 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 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). 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 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 in 
May and October of each year (http://

[[Page 45648]]

www.cdc.gov/nchs/nhanes/nh3data_genetic.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: August 27, 2009.
Tanja Popovic,
Chief Science Officer, Centers for Disease Contro and Prevention.
[FR Doc. E9-21287 Filed 9-2-09; 8:45 am]
BILLING CODE 4163-18-P