[Federal Register Volume 72, Number 201 (Thursday, October 18, 2007)]
[Notices]
[Pages 59094-59098]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-20592]


-----------------------------------------------------------------------

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 (CDC), Department of 
Health and Human Services (HHS).

ACTION: Notice.

-----------------------------------------------------------------------

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 noninstitutionalized 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 two 
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 1999-2002 NHANES survey years. All specimens (NHANES III and 
NHANES 1999-2002 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 
begin to accept proposals after the publication of this notice and will 
continue to accept proposals on an on-going basis.
    Proposals received within 60 days of the notice will complete 
review approximately 180 days after the notice is published. After this 
initial review of proposals, all proposal categories will be reviewed 
twice a year beginning January 1 and July 1 of each year. Unforeseen 
circumstances could result in a change to this schedule. 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: December 17, 2007, and 
thereafter on January 1 and July 1.
     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: Christopher 
Sanders, Division of Health and Nutrition Examination Surveys, National 
Center for Health Statistics, Centers for Disease Control and 
Prevention, 3311 Toledo Road, Room 4203, Hyattsville, MD 20782, Phone: 
301-458-4840, FAX: 301-458-4028, E-mail: [email protected].

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

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] and Friday, January 
13, 2006 [71 FR 22248]). 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. 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). The data release cycle for the NHANES during the 
period in which DNA specimens were collected is described as NHANES 
1999-2000 and NHANES 2001-2002.

[[Page 59095]]

    See: http://www.cdc.gov/nchs/about/major/nhanes/nhanes99_00.htm or 
http://www.cdc.gov/nchs/about/major/nhanes/nhanes01-02.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, 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 
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 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, 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) for selected genes and relating these 
findings to demographic data or demographic and phenotypic data 
available from NHANES. This category is open for proposals for use of 
NHANES III or NHANES 1999-2002 samples. A total of ten full sets of 
samples for each survey cycle will be available for any review cycle. 
The investigator will specify which DNA bank, NHANES III or NHANES 
1999-2002, 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 Research Data Center (RDC) or its 
equivalent.
    Proposals are limited to the testing of 3,000 genetic variations or 
less because CDC has proposals to perform whole genome analysis on 
these samples under review.
    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/about/major/nhanes/genetic.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 7,157 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.

    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.

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 ul. 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 DNA Samples

    The laboratory will distribute aliquots of purified DNA of 
normalized concentrations of 50 nanograms per microliter 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 (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.
    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]). The 
additional cost for the NHANES 1999-2002 samples is due to the 
increased costs associated with DNA purification and normalization of 
this collection.

[[Page 59096]]



--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                              Cost per sample  partial
           Total costs             Cost per sample  full set,     Cost per sample  partial     Cost per sample  full set,    set,  NHANES III  (special
                                              99-02                 set, 99-02  (special               NHANES III                     request)
--------------------------------------------------------------------------request)----------------------------------------------------------------------
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.....  $63,024.00                    NA                            $42,596.36                    NA
                                 =======================================================================================================================
    Total cost per category B     6,302                         10 percent of original cost   4,260                         10 percent of original cost
     proposal: for Data handling.                                of samples                                                  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 or B) submitted. OHRP 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 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.

[[Page 59097]]

Researchers should justify that the test 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 
proposals that use the full set of approximately 7,900 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/about/major/nhanes/genetic.htm. Proposals for secondary data analyses linking NHANES 
public use data with genetic variation data are accepted in May and 
October of each year.
    Proposals reviewed by a Genetics Technical Panel and the Secondary 
Review Panel will be reviewed by the CDC/NCHS Ethics Review Board (ERB) 
to ensure appropriate for 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 indicate 
the reason for analyzing race/ethnicity and how the results will be 
interpreted.
    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: Christopher Sanders, Division of Health and 
Nutrition Examination Surveys, National Center for Health Statistics, 
Centers for Disease Control and Prevention, 3311 Toledo Road, Room 
4203, 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 or NHANES 1999-2002 
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. An ERB 
continuation form will be sent to the researcher each year for project 
update.
    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://www.cdc.gov/nchs/about/major/nhanes/genetic.htm).
    Send Requests for Information: Christopher Sanders, Division of 
Health and Nutrition Examination Surveys, National Center for Health 
Statistics, Centers for Disease Control and Prevention, 3311 Toledo 
Road, Room 4203, Hyattsville, MD 20782, Phone: 301-458-4840. FAX: 301-
458-4028. E-mail: [email protected].


[[Page 59098]]


    Dated: October 11, 2007.
James D. Seligman,
Chief Information Officer, Centers for Disease Control and Prevention.
 [FR Doc. E7-20592 Filed 10-17-07; 8:45 am]
BILLING CODE 4163-18-P