Notice2022-14702
National Health and Nutrition Examination Survey (NHANES) Stored DNA Specimens; Proposed Cost Schedule and Guidelines for Proposal To Use DNA Specimens
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Published
July 11, 2022
Effective
July 11, 2022
Issuing agencies
Health and Human Services DepartmentCenters for Disease Control and Prevention
Abstract
The Centers for Disease Control and Prevention (CDC), located within the Department of Health and Human Services (HHS), announces the availability of stored DNA specimens obtained from participants in the National Health and Nutrition Examination Survey (NHANES) and the proposal parameters and fee schedule for use. NHANES is one of a series of health-related surveys conducted by CDC's National Center for Health Statistics (NCHS).
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<title>Federal Register, Volume 87 Issue 131 (Monday, July 11, 2022)</title>
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[Federal Register Volume 87, Number 131 (Monday, July 11, 2022)]
[Notices]
[Pages 41129-41132]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-14702]
[[Page 41129]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
National Health and Nutrition Examination Survey (NHANES) Stored
DNA Specimens; Proposed Cost Schedule and Guidelines for Proposal To
Use DNA Specimens
AGENCY: Centers for Disease Control and Prevention (CDC), Department of
Health and Human Services (HHS).
ACTION: Notice.
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SUMMARY: The Centers for Disease Control and Prevention (CDC), located
within the Department of Health and Human Services (HHS), announces the
availability of stored DNA specimens obtained from participants in the
National Health and Nutrition Examination Survey (NHANES) and the
proposal parameters and fee schedule for use. NHANES is one of a series
of health-related surveys conducted by CDC's National Center for Health
Statistics (NCHS).
DATES: The stored NHANES DNA specimens are available July 11, 2022. The
fee structure for these specimens is effective July 11, 2022.
FOR FURTHER INFORMATION CONTACT: Jody McLean, Division of Health and
Nutrition Examination Surveys, National Center for Health Statistics,
Centers for Disease Control and Prevention, 3311 Toledo Road,
Hyattsville, MD 20782, Telephone: (301) 458-4683; Email:
<a href="/cdn-cgi/l/email-protection#17595f5659524470727972637e74645774737439707861"><span class="__cf_email__" data-cfemail="da94929b949f89bdbfb4bfaeb3b9a99ab9beb9f4bdb5ac">[email protected]</span></a>.
Authority: Sections 301,306 and 308 of the Public Health Service
Act (42 U.S.C. 241, 242k, and 242m).
SUPPLEMENTARY INFORMATION:
Background: NHANES is a program of periodic surveys conducted by
NCHS. NHANES has provided national estimates of the health and
nutritional status of the U.S. civilian non-institutionalized
population since the 1960s. 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; and (7) to establish and maintain a national probability
sample of baseline information on health and nutritional status.
DNA Specimens, Availability, and Resulting Data
The availability of the NHANES III Phase 2 DNA specimens was first
announced in 2002. NHANES III Phase 2 DNA specimens (1991-1994) are
from participants ages 12 or older (see: <a href="https://wwwn.cdc.gov/nchs/nhanes/nhanes3/default.aspx">https://wwwn.cdc.gov/nchs/nhanes/nhanes3/default.aspx</a> for more information on NHANES III).
NHANES III Phase 2 DNA specimens are crude DNA lysates extracted
from cell lines; therefore, DNA concentrations vary and are estimated
to range from 7.5-65.0 ng/[mu]L with an average of approximately four
micrograms in 100 [mu]L. DNA specimens are available from 7,159 NHANES
III Phase 2 participants. Forty microliters of each DNA specimen will
be distributed in 82 plates, including four plates of quality control
specimens. NHANES III DNA specimens are in limited supply and thus are
not available as a partial set (which is a request for less than the
total number of participants available). Due to the extraction method,
NHANES III DNA specimens are not appropriate for all projects and
assays. For background information on all DNA specimens, see the NHANES
Biospecimen Program report at <a href="https://www.cdc.gov/nchs/data/series/sr_02/sr02_170.pdf">https://www.cdc.gov/nchs/data/series/sr_02/sr02_170.pdf</a>.
In 1999, NHANES became a continuous survey, with data released
every two years (see <a href="https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx">https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx</a> for more information on continuous NHANES). The
availability of DNA specimens from the continuous NHANES was first
announced in 2007.
Continuous NHANES DNA specimens are available as collections from
NHANES 1999-2002 (NHANES 1999-2000 and 2001-2002 specimens are
available as one collection) and NHANES two-year cycles 2007-08, 2009-
10, and 2011-12. In continuous NHANES, DNA was purified from whole
blood; aliquots of DNA were normalized to concentrations of
approximately 50 ng/[micro]l, and 40 [micro]l of each DNA specimen will
be distributed. There are purified DNA specimens from 7,830 NHANES
1999-2002 participants. These specimens will be distributed into 90
plates, including four plates of quality control specimens. There are
purified DNA specimens available from 4,612 NHANES 2007-2008
participants. These will be distributed into approximately 54 plates,
including three plates of quality control specimens. There are purified
DNA specimens available from 4,893 NHANES 2009-2010 participants. These
will be distributed into 58 plates, including three additional plates
of quality control specimens. There are purified DNA specimens
available from 4,147 NHANES 2011-12 participants. These will be
distributed into 49 plates, including three additional plates of
quality control specimens.
DNA specimens will be available for testing only from participants
who consented to future research.
The resulting data from DNA specimen testing will be linkable to
variables (public use and restricted) and available for analyses
through the NCHS Research Data Center (RDC; <a href="https://www.cdc.gov/rdc/index.htm">https://www.cdc.gov/rdc/index.htm</a>) for approved proposals unless otherwise determined by the
NHANES Project Officer. Access to these data at the NCHS RDC is only
through an approved proposal process mechanism to assure
confidentiality (see ``APPROVED PROPOSALS: Post-Testing Procedures''
section).
Parameters for DNA Specimen Use and Resulting Data
1. Investigators must justify why they need a specimen from a
national probability sample of the U.S. population for their study.
2. Investigators must specify which NHANES cycles they are
requesting DNA specimens from and the specific laboratory tests to be
conducted on those specified DNA specimens.
3. Only those proposals for which the laboratory testing will
result in findings determined not to have clinical significance for
participants will be approved. The consent document for DNA storage and
future research use of DNA specimens states that individual results
will not be provided to participants. Therefore, no proposals involving
tests with clinical significance will be approved. DHANES/NCHS will use
the most recent American College of Medical Genetics and Genomics
(ACMG) recommendations for reporting secondary findings \1\ to assess
the proposed tests and their potential for yielding clinically
significant findings. Investigators must verify that the proposed tests
do not produce variants (e.g., single-nucleotide polymorphisms,
[[Page 41130]]
translocation and inversions, copy number variations) on specific genes
listed by the most recent ACMG recommendations as reportable secondary
findings and describe how potential secondary findings results will be
handled.
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\1\ See ``Guidelines for Returning Individual Results from
Genome Research Using Population-Based Banked Specimens'' (<a href="https://nap.nationalacademies.org/catalog/18829/issues-in-returning-individual-results-from-genome-research-using-population-based-banked-specimens-with-a-focus-on-the-national-health-and-nutrition-examination-survey">https://nap.nationalacademies.org/catalog/18829/issues-in-returning-individual-results-from-genome-research-using-population-based-banked-specimens-with-a-focus-on-the-national-health-and-nutrition-examination-survey</a>), convened by the National Academies of Science
Committee on National Statistics in 2014 at the request of NCHS's
Board of Scientific Counselors.
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4. Upon receipt of the specimen and after conducting the approved
testing, investigators must provide a copy of the resulting data
obtained from DNA testing to the Division of Health and Nutrition
Examination Survey (DHANES)/NCHS for quality control assessment.
5. After DHANES/NCHS has completed the initial quality control
assessment of submitted data, investigators will be given up to six
months to conduct a comprehensive quality assurance review. At this
review's completion, the resulting data's availability will be publicly
announced on the NHANES website Genetic Variant Search: <a href="http://www.nhgeneticvariant.com/">http://www.nhgeneticvariant.com/</a>. The resulting data can be linked to other
NCHS variables (public use and restricted) for secondary data analysis.
Analysis and linkage of the resulting data are conducted in the NCHS
RDC via a separate proposal unless otherwise determined by the NHANES
Project Officer (see ``APPROVED PROPOSALS: Post-Testing Procedures''
section).
Proposals Testing DNA Specimens Already Obtained From Previous
Solicitations
Investigators who have obtained NHANES DNA specimens from previous
solicitations and have sufficient DNA left may request to do additional
tests on the remaining DNA. These proposals must be submitted and
approved as further provided herein. The investigator must pay an
additional cost (see ``COST SCHEDULE'' section) per each additional
proposal).
Proposal Evaluation
All proposals for the use of NHANES DNA specimens will be evaluated
by the NHANES Project Officer, a Technical Panel, the NCHS
Confidentiality Officer, the NCHS Human Subjects Contact, and the NCHS
Ethics Review Board (ERB). Applications will have a Scientific Review
by the NHANES Project Officer and the Technical Panel. The Technical
Panel comprises two members with subject matter expertise: one from CDC
staff and one external to CDC, i.e., from other federal agencies,
academia, or industry. Only technical panel members with no conflict of
interest and no previous knowledge of the research project will be
asked to review the proposal. The members review each proposal for
scientific and technical merit and ensure that the proposed project
does not go beyond the general purpose of collecting the blood
specimens for DNA in NHANES (see ``PROCEDURES FOR PROPOSALS'' section).
After the proposal is approved by the NHANES Project Officer and
the Technical Panel, it will be submitted for Institutional Review. All
proposals will undergo Institutional Review by the NCHS Human Subjects
Contact and the NCHS ERB for any potential human subjects concerns to
ensure appropriate human subjects protections are provided in
compliance with 45 CFR 46 and by the NCHS Confidentiality Officer for
disclosure risk. The NCHS ERB will review the proposal even if the
investigators have received approval from their institutional review
panel. The proposal, if approved, will become an amendment to the
current NHANES ERB Protocol (i.e., the NHANES ERB Protocol that is in
effect at the time of the investigator's proposal approval).
If a proposal is approved, the author's title, specific aims, name,
and phone number will be maintained by NCHS and released if requested
by the public. NCHS will not maintain unapproved proposals.
Procedures for Proposals
All investigators (including CDC investigators) must submit a
proposal for the use of NHANES DNA specimens and follow the
instructions as set forth herein, including following the outline set
out below. Proposals should be a maximum of 20 1.5-spaced typed pages,
excluding figures and tables, using at least size 10 font. The cover of
the proposal (which is not included in the 20-page limit) should
include the title of the proposal, the name, address, phone number, and
email address of the principal investigator (PI), and the name of the
institution where the laboratory analysis will be done. The name,
address, phone number, and email address of all additional
investigators should also be included on the cover. Office of Human
Research Protections assurance numbers for the institutions in the
proposed project should be included. CDC investigators must include the
expiration date of their Collaborative Institutional Training
Initiative (CITI) training. All proposals should be submitted via email
to <a href="/cdn-cgi/l/email-protection#307e78717e756357555e5544595343705354531e575f46"><span class="__cf_email__" data-cfemail="c48a8c858a8197a3a1aaa1b0ada7b784a7a0a7eaa3abb2">[email protected]</span></a>. Note: If the investigator would like to
propose a subsample of the complete set, please contact the NHANES
Project Officer to discuss feasibility.
The following criteria will be used for technical evaluation of
proposals:
(1) Abstract: Please limit the abstract to 300 words.
(2) Specific Aims: List the broad objectives; describe concisely
and realistically what the proposed project is intended to accomplish
and state the specific hypotheses to be tested.
(3) Background and Public Health Significance:
(A) Describe the public health significance of the proposed study.
(B) Discuss how the results will be used. Analyses should be
consistent with the NHANES mission to assess the health of the nation.
The Scientific Review will ensure that the proposed project does not go
beyond the general purpose of collecting the blood specimens for DNA in
the survey or the specific stated goals of the proposal.
(4) Design, Method, and Analytic Plan: The appropriateness and
adequacy of the methodology proposed to reach the specific aims and 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.
(A) Study Design and Methods: Include a detailed description of the
laboratory methods. The characteristics of the laboratory assay, such
as reliability, and validity, should be included with appropriate
references. The laboratory must demonstrate expertise in the proposed
test, including the capability to handle the workload requested in the
proposal. The potential difficulties and limitations of the proposed
procedures should also be discussed. Address methods to ensure adequate
handling and storage of DNA specimens. Proposals must specify variants
or the commercial assay(s) used to test the proposed research
hypotheses and include a statement of why the specific standard
assay(s) is/are necessary to test the proposed hypotheses. Note: A
standard assay is a commercially available assay for a curated set of
variants or biological markers. Investigators who submit successful
proposals will be provided with quality control specimens at no
additional cost. Approved projects must run these quality control
specimens and submit these results along with the results from the
NHANES DNA specimens unless the NHANES Project Officer has approved an
alternative quality control review plan. The proposal should address
any additional quality control procedures the laboratory will use to
assure the validity of the test results and address methods to ensure
adequate handling and storage of specimens.
[[Page 41131]]
(B) Analytic Plan: Describe the data analysis and statistical
methods to be employed. Include power calculations. Resulting data from
DNA specimens are restricted access data and must be analyzed in the
NCHS RDC. The proposal should state that the data analysis will be
conducted in the RDC unless DHANES/NCHS determines otherwise.
(5) Additional information for NHANES:
(A) Clinical Significance of Results: The consent document for DNA
specimen storage and future studies states that individual results will
not be provided to participants; therefore, no tests that need to be
reported back to the participant can be proposed. DHANES/NCHS will use
the most recent American College of Medical Genetics and Genomics
(ACMG) recommendations for reporting secondary findings to review the
proposed tests and the potential secondary findings. Investigators must
verify that the proposed tests do not produce variants on specific
genes listed by the most recent ACMG recommendations as reportable
secondary findings and describe how potential secondary test results
will be handled. The 2021 statement, ``ACMG SF v3.0 list for reporting
of secondary findings in clinical exome and genome sequencing: a policy
statement of the American College of Medical Genetics and Genomics
(ACMG),'' lists 73 genes where specific variants on these genes are
pathogenic for 34 conditions.
(B) Data Transfer: Specify the secure method to transfer the
resulting data to NCHS. Investigators must use a device that meets
federal information processing standards (FIPS 140-2 and FIPS 197).
(C) Period of Performance: Specify the proposed project period.
Substantial progress must be made in the first year that specimens have
been obtained, and the project should be completed within a reasonable
period of time. Please discuss the approximate time the investigator
expects this project will take to complete. The NHANES Project Officer
must be consulted about the disposition of the specimens. At the end of
the project period, any unused specimens must be returned to the NHANES
DNA Specimen Repository or destroyed by the investigator.
(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 specimens (see
COST SCHEDULE FOR PROVIDING NHANES DNA SPECIMENS and Cost Schedule for
NHANES DNA Specimens for details).
(6) Resumes/CV: Please include a two-page CV for each member of the
study team in the proposal (not as attachments; CVs do not count
towards page maximum).
Submission of Proposals
Proposals must be submitted in MS Word format by email to
<a href="/cdn-cgi/l/email-protection#4c02040d02091f2b29222938252f3f0c2f282f622b233a"><span class="__cf_email__" data-cfemail="b6f8fef7f8f3e5d1d3d8d3c2dfd5c5f6d5d2d598d1d9c0">[email protected]</span></a>.
Proposal Timeframes
<bullet> Submission of Proposals: Can be submitted on an ongoing basis
<bullet> Scientific Review: Completed approximately two months after
proposal submission
<bullet> Institutional Review: Completed approximately six weeks after
completion of scientific review
<bullet> Notification of Approval: Approximately 30 days after
completion of Institutional Review
<bullet> Anticipated Distribution of Specimens: Approximately 60 days
after the following is completed: notification of proposal approval,
agreements signed (as described below), and payments received (as
described below)
Note: Timeframes 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.
Approved Proposals
Investigators must transfer payment to DHANES/NCHS and sign terms
and conditions agreements for the use of the DNA specimens with CDC/
NCHS before releasing the NHANES DNA specimens. Investigator(s) must
agree to: (a) use the specimens only for the approved tests; (b) use
the test results only for purposes as stated in the approved proposal;
(c) not link the results of the proposed project to any other data; (d)
not use the DNA specimens for commercial purposes, as set forth in a
legally binding Materials Transfer Agreement (MTA; if non-government
investigators) or Interagency Agreement (IAA; if government
investigators); and (e) sign and abide by a Designated Agent Agreement
(DAA) with CDC/NCHS in accordance with NCHS' confidentiality
legislation.
Agency Agreements
A formal signed agreement, embodied in the form of an MTA or an
IAA, and a DAA with investigators who have projects approved, must be
completed before the release of the specimens to the investigator. For
the MTA or IAA, this agreement will contain the conditions for use of
the specimens as stated in this Federal Register notice and as agreed
upon by the investigators and CDC. The DAA is the mechanism by which
CDC/NCHS may authorize the designation of agents to exclusively perform
activities needed to produce approved data using the Confidential
Information Protection and Statistical Efficiency Act (CIPSEA; Title V
of the E-Government Act of 2002 [Pub. L. 107-347])-protected NHANES DNA
specimens. The DAA must be signed by the investigator taking custody of
DNA specimens and producing resulting data.
Continuations
A brief progress report must be submitted annually to NHANES. This
report should describe the work completed and the timeline to project
completion. When five years have elapsed since the initial approval of
the proposal by the NCHS ERB, the investigator must provide an updated
project timeline to complete the study for approval by NHANES. If a new
investigator(s) is added at any time during the project, or the
Principal Investigator has changed, the NHANES Project Officer must be
notified.
Approved Proposals: Post-Testing Procedures
After DNA specimens are received and testing is complete, the
investigators must send the resulting data back for DHANES/NCHS quality
control assessment. While DHANES/NCHS quality control assessment is
underway, the investigator can submit an NCHS RDC proposal (<a href="http://www.cdc.gov/rdc">http://www.cdc.gov/rdc</a>) to conduct an additional quality assurance review. The
vast majority of resulting data from DNA specimens is restricted;
therefore, the data are available only in the NCHS RDC. Once the
investigators' quality assurance review is complete and the results are
returned to DHANES/NCHS, investigators will be given up to six months
to conduct a comprehensive quality assurance review in the NCHS RDC.
The quality assurance review timeframe will be negotiated between the
investigators and the NHANES Project Officer and will depend on the
type, number, and characteristics of the tests submitted. The results
of the quality assurance review will be provided to DHANES/NCHS, and
appropriate aspects will become part of the data set documentation. The
public announcement, informing that test results are available for
secondary data analyses after submission and acceptance of proposals,
will occur once the quality assurance review timeframe has ended. For a
list of currently
[[Page 41132]]
available variant data, see: <a href="http://www.nhgeneticvariant.com/">http://www.nhgeneticvariant.com/</a>.
A minority of resulting data from DNA specimens are not restricted.
In these cases, the resulting data will undergo disclosure review by
the NCHS Confidentiality Officer and NCHS Disclosure Review Board or
designee before the linked data are sent to the investigators for
quality control review. Once approved by disclosure review and after
the investigators have signed the Data Sharing Agreement, the linked
data file will be sent to the investigators for use pursuant to the
terms of the relevant agreement. The quality control review must take
place within 60 days or a negotiated length of time, and the return of
the data to NCHS within the next 30 days so these data may be released
to the public.
Disposition of Specimens
The provided DNA specimens cannot be used for any purpose other
than the specifically requested purpose outlined in the proposal and
approved through the Scientific and Institutional Review. No DNA
specimens can be shared with others, including other investigators,
unless specified in the proposal and so approved. Specimens must be
returned upon completion of the approved project or destroyed. Both
options require written approval from the NHANES Project Officer.
Cost Schedule for Providing NHANES DNA Specimens
There is a nominal processing fee of $17.17 for each DNA specimen
received from an NHANES DNA Repository. The costs include collecting,
processing, storing, and retrieving the DNA specimens, reviewing
proposals, and preparing the data files. The costs listed are for the
recurring laboratory materials to dispense and prepare the DNA
specimens during collection and shipping. The NHANES DNA Specimen
repository costs include long-term storage (including inventory
management and materials and equipment) and accessioning of specimens
and specimen retrieval for shipment to the investigator. Labor costs
are based on a proposal administrator to manage the proposal process
and computer programmers at NCHS who prepare the data files for the
release of the data along with documentation on the NHANES web page. If
the investigators request to use the DNA specimens for another proposed
project after the completion of the initial project, the additional
cost will be 5 percent of the specimen set cost to handle the
processing of the data and management of the subsequent proposal
process. A new proposal must be submitted and go through the approval
process before any additional use of the DNA specimens.
Cost Schedule for NHANES DNA Specimens
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1999-2002, 1999-2002,
2007-2008, 2007-2008,
Total costs 2009-2010, 2009-2010, NHANES III
2011-2012 2011-2012 complete set
complete sets partial set
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Materials and equipment--contractor: plates, reagents, $1.72 $5.15 $0.85
assays, aliquoting and packaging specimens; use of
equipment..................................................
Labor--contractor: processing, handling, and shipping; NCHS: 5.66 28.31 2.83
data quality control.......................................
Proposal review and administrative expenses--contractor: 3.43 6.87 1.72
inventory management and reporting; NCHS: management of
proposal process non-NCHS: technical panel fees............
Space--contractor: freezer use and maintenance.............. 6.36 6.36 3.17
Cost per specimen........................................... 17.17 46.69 8.58
Cost per new proposal:
1999-2002................................................... 134,430.92 *
2007-2008................................................... 79,181.82 *
2009-2010................................................... 84,006.11 *
2011-2012................................................... 71,181.89 *
III......................................................... .............. .............. 61,454.85
Cost per additional proposal: **
1999-2002................................................... 6,721.94 ***
2007-2008................................................... 4,130.72 ***
2009-2010................................................... 4,200.08 ***
2011-2012................................................... 3,559.95 ***
III......................................................... .............. .............. 3,072.17
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* Cost calculated upon request.
** Additional research using DNA specimens already obtained from previous solicitations.
*** This charge will be 5 percent of the original cost.
Note: Applicable CDC overhead and NCHS management and oversight charges will be added to these rates for
proposals coming from federal agencies.
Angela K. Oliver,
Executive Secretary, Centers for Disease Control and Prevention.
[FR Doc. 2022-14702 Filed 7-8-22; 8:45 am]
BILLING CODE 4163-18-P
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