[Federal Register: October 18, 2007 (Volume 72, Number 201)]
[Notices]
[Page 59094-59098]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18oc07-51]
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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 (CDC), Department of
Health and Human Services (HHS).
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 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: NHANESgenetics@cdc.gov.
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]]
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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
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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
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TOTAL COST PER PROPOSAL..... $63,024.00 NA $42,596.36 NA
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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
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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: NHANESgenetics@cdc.gov.
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: NHANESgenetics@cdc.gov.
[[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