[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
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Subtotal........................ 6.20 31.70 4.63 27.56
NCHS overhead (18 percent).......... 1.12 5.71 0.83 4.97
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Subtotal........................ 7.32 37.41 5.46 32.52
CDC/FMO overhead (0.9 percent)...... 0.66 3.37 0.49 2.93
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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