[Federal Register Volume 86, Number 153 (Thursday, August 12, 2021)]
[Notices]
[Pages 44367-44370]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-17265]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention


National Health and Nutrition Examination Survey (NHANES) Stored 
Biologic Samples; Proposed Cost Schedule and Guidelines for Proposals 
To Use Serum, Plasma, and Urine Samples

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) in the 
Department of Health and Human Services (HHS) announces the 
availability of stored serum, plasma, and urine samples obtained from 
participants in the National Health and Nutrition Examination Survey 
(NHANES) and the proposal parameters and fee schedule for use. The 
National Health and Nutrition Examination Survey (NHANES) is one of a 
series of health-related surveys conducted by CDC's National Center for 
Health Statistics (NCHS).

DATES: The stored NHANES biologic samples are available August 12, 
2021. The fee structure for these samples is effective August 12, 2021.

FOR FURTHER INFORMATION CONTACT: Bryan Stierman, National Center for 
Health Statistics, Centers for Disease Control and Prevention, 3311 
Toledo Road, Hyattsville, MD 20782. Telephone: (301) 458-4798. Email: 
[email protected]v.

SUPPLEMENTARY INFORMATION: NHANES is a program of periodic surveys 
conducted by NCHS. 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. The goals of 
NHANES are: (1) To estimate the number and percent of persons in the 
U.S. population and designated subgroups with selected diseases and 
risk factors; (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 relationship between 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 nutrition 
status.
    For NHANES cycles prior to the 2021-22 cycle, the survey 
oversamples the two largest race/ethnicity groups, non-Hispanic black 
and Mexican American (and all Hispanic since 2007-08). In 2011-2020, 
NHANES also oversampled the Asian race/ethnicity group.

Sample Availability

    Samples are available from NHANES III, a periodic survey that was 
conducted from 1988-1994 (see: https://wwwn.cdc.gov/nchs/nhanes/nhanes3/default.aspx for more information on NHANES III), and the 
continuous NHANES, with data release in two-year cycles starting in 
1999-2000 through the 2019-March 2020 (Coronavirus Disease 2019 (COVID-
19) pre-pandemic) (Table A) collection. NCHS is making both collections 
available for study proposals.
    Approximately 30,000 individuals were examined in NHANES III, which 
began in the fall of 1988, and ended in the fall of 1994. Investigators 
can analyze samples from this survey in two phases. Phase 1 was 
conducted from October 1988 to October 1991 and Phase 2 began October 
1991 and ended October 1994.
    Beginning in 1999, NHANES became a continuous, annual survey with 
examination of approximately 5,000 individuals a year and data release 
every two years. Samples from a single year of the survey will only be 
provided in emergency situations (outbreaks). Projects must use two-
year cycles or multiple two-year cycles for their studies (i.e., 1999-
2000, 2001-2002 etc.).
    Serum, plasma, and urine samples are stored in two biorepositories. 
Samples that were initially used for laboratory assays included in the 
surveys, that were stored at -70[deg]C and that have been through at 
least two freeze-thaw cycles, are considered surplus samples. They are 
stored at a commercial biorepository under contract to NCHS. In 
addition, another set of serum, plasma, and urine samples were also 
stored immediately after collection at -80[deg]C or below in vapor-
phase liquid nitrogen. These samples have not undergone a freeze-thaw 
cycle and are considered pristine samples. The CDC Biorepository (CBR) 
is the long-term repository for the pristine NHANES serum, plasma, and 
urine samples. NCHS is making both pristine and surplus collections 
available for study proposals. Please see the NHANES Biospecimen 
Program series report for details about collection and storage of 
serum, plasma, and urine samples http://www.cdc.gov/nchs/data/series/sr_02/sr02_170.pdf.

                           Table A--Overview of Biospecimens by Survey Year, NHANES III (1988-1994) and NHANES 1999-March 2020
                                                                     [Pre-pandemic]
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                                                                                                 Sample type
                                                   -----------------------------------------------------------------------------------------------------
                   NHANES cycle                                        Pristine \1\                                       Surplus \2\
                                                   -----------------------------------------------------------------------------------------------------
                                                          Sera            Plasma           Urine             Sera            Plasma           Urine
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III (1988-1994)...................................               X   ...............  ...............               X   ...............  ...............
1999-2000.........................................               X                X                X                X                X   ...............
2001-2002.........................................               X                X                X                X                X   ...............
2003-2004.........................................               X                X                X                X   ...............  ...............
2005-2006.........................................               X                X                X                X   ...............  ...............
2007-2008.........................................               X                X                X                X                X   ...............

[[Page 44368]]

 
2009-2010.........................................               X                X                X                X   ...............  ...............
2011-2012.........................................               X   ...............               X                X   ...............  ...............
2013-2014.........................................               X   ...............               X                X   ...............  ...............
2015-2016.........................................               X   ...............               X                X   ...............  ...............
2017-2018.........................................               X   ...............               X                X   ...............  ...............
2019--March pre-pandemic 2020.....................               X   ...............               X                X   ...............  ...............
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\1\ Samples immediately frozen for storage, did not undergo laboratory testing.
\2\ Samples are surplus specimens after laboratories had completed testing.

Parameters for Sample Use

    1. Investigators should justify why they need a national 
probability sample for their study.
    2. To assure the representative nature of NHANES, at least a \1/3\ 
sample of a two-year cycle must be requested for an individual 
proposal. For details of the sampling design, see the Analytic 
Guidelines at: https://wwwn.cdc.gov/nchs/nhanes/analyticguidelines.aspx.
    3. Investigators that request pristine (never thawed) samples 
should justify the use of the pristine samples.
    4. Only proposals with test results that are determined not to have 
clinical significance for participants will be accepted. Starting in 
1999, the consent form informed participants that they would not 
receive results from any future laboratory analysis that may be 
conducted on their samples. Though the consent form for NHANES III had 
less detail, this parameter is also applicable to the use of NHANES III 
samples. Therefore, only proposals with laboratory test results that do 
not have clinical significance to the survey participant will be 
accepted. The potential for clinical significance of a laboratory test 
should be addressed by investigators in the proposal; the determination 
of clinical significance will be made by the Technical Panel. A 
laboratory test result is considered clinically significant to the 
survey participant if the following criteria are met:
     The laboratory test is performed by a Clinical Laboratory 
Improvement Amendments (CLIA)- certified laboratory deeming the 
findings valid,
     the findings have significant implications for the 
participant's health concerns, and
     a course of action is readily available to treat the 
associated health concern

Proposal Evaluation

    All proposals for use of NHANES samples will be evaluated by a 
Technical Panel, the NCHS Confidentiality Officer, the NCHS Human 
Subjects Contact and the NCHS Ethics Review Board (ERB). The current 
Technical Panel consists of NHANES staff: Two physicians, one 
statistician and a laboratory expert. Other experts from inside or 
outside the Federal Government are added as needed. The Technical Panel 
reviews proposals for scientific merit to determine: The need to use a 
nationally representative sample, public health significance, and 
laboratory assay validity, and potential for clinical significance to 
the participant. The NCHS Confidentiality Officer reviews for 
disclosure risk; the NCHS Human Subjects Officer for potential human 
subjects concerns; and the NCHS ERB for conforming to the informed 
consent. The NCHS ERB will review the proposal even if the investigator 
has received approval by their respective 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 and held at NCHS).
    The Technical Panel will evaluate the proposal for the scientific, 
technical, and clinical significance to the participant, the 
appropriateness and adequacy of the study design, and the methodology 
proposed to reach the study goals. See ``Procedures for Proposals'' 
below. The proposal should outline how the results from the laboratory 
analysis will be used. Because NHANES is a complex, multistage 
probability sample of the U.S. population, the appropriateness of the 
NHANES sample to address the goals of the proposal will be an important 
aspect of scientific merit.
    Sampling weights are therefore used to make national estimates of 
frequencies. The use of weights, sampling frame and methods of 
assessment of variables included in the data are likely to affect the 
proposed study. For this reason, investigators submitting proposals are 
required to request at least a \1/3\ sample of a NHANES cycle to 
maintain the representative nature of the survey.
    The Technical Panel will also review the data analysis plan and 
evaluate whether the proposal is an appropriate use of the NHANES 
samples. The investigators should justify why they need a national 
probability sample for their study. The Technical Panel review will 
seek to assure that the proposed project does not go beyond either the 
general purpose for collecting the samples in the survey, or of the 
specific stated goals of the NHANES proposal.
    Investigators are encouraged to review the NHANES data, survey 
documents, manuals and questionnaires at: NHANES Questionnaires, 
Datasets, and Related Documentation (cdc.gov) or for NHANES III: 
https://wwwn.cdc.gov/nchs/nhanes/nhanes3/datafiles.aspx

Procedures for Proposals

    All investigators (including CDC investigators) must submit a 
proposal for use of NHANES serum, plasma, or urine samples. Proposals 
are limited to a maximum of 10 single-spaced typed pages, excluding 
figures and tables, using at least a size 10 font. The cover of the 
proposal (which is not included in the 10-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. All proposals should be Emailed 
to

[[Page 44369]]

[email protected]v. Proposals from CDC investigators must also 
include the investigator's Collaborative Institutional Training 
Initiative (CITI) expiration date.
    The following criteria will be used for technical evaluation of 
proposals:
    Proposals should include the following information:
    (1) Specific Aims: List the broad objectives; describe concisely 
and realistically what the study is intended to accomplish and state 
the specific hypotheses to be tested. NHANES is designed to provide 
prevalence estimates of diseases or conditions that are expected to 
affect at least 5-10 percent of the population. Proposals that expect 
much lower prevalence estimates need to provide more detail on why 
samples from NHANES are needed for the project and provide details on 
how these data will be analyzed.
    (2) Background and Public Health Significance: Describe the public 
health significance, scientific merit, and practical utility of the 
assay. Briefly describe in 1-2 pages the background of the proposal, 
identifying gaps in knowledge that the project is intended to fill. 
State concisely the importance of the study in terms of the broad, 
long-term objectives and public health relevance including a discussion 
of how the results will affect public health policy or further 
scientific knowledge. The proposal should justify the need for samples 
that are representative of the U.S. population. The investigator should 
convey how the results will be used and the relationship of the results 
to the data already collected in NHANES. The analyses should be 
consistent with the NHANES mission and the health status variables.
    (3) Study Design and Methods: Describe the study design, analytic 
plan, and the procedures to be used. A detailed description of 
laboratory methods including validity and reliability must be included 
with references. The volume of sample and number of samples requested 
must be specified. Adequate methods for handling and storage of samples 
must also be addressed. The laboratory must demonstrate expertise in 
the proposed laboratory test including the capability for handling the 
workload requested in the proposal. The proposal should also include a 
justification for determination of sample size or a power calculation. 
If the investigator is requesting a sub-sample of samples, a detailed 
description and justification must be given.
    The Technical Panel will evaluate the Investigator's submitted 
proposal study design and analysis plan to determine whether the 
project is consistent with the design of the NHANES survey. The 
resulting data will be released in the public domain or in rare 
occasions to the NCHS Research Data Center by NCHS (if there is a 
disclosure concern, e.g. one year of NHANES cycle). Released data from 
sub-samples may be less useful to the scientific community, so such 
requests will receive a lower priority for obtaining the samples.
    (4) Clinical Significance of Results: Address the clinical 
significance to the survey participant of the proposed laboratory test. 
Since the consent document for sample storage and future studies states 
that individual results will not be provided to the participant, the 
investigator must address whether there is evidence that the proposed 
test results have health implications to the participants and whether 
knowledge of results would provide grounds for medical intervention 
(even if many years have passed since the participant was in the survey 
and the sample collected). Any test with results that are clinically 
significant, and would require reporting to the participant, is not 
appropriate for testing on the stored serum, plasma, or urine samples 
and will not be approved; laboratory testing that is clinically 
significant should be considered for inclusion in a future NHANES 
survey cycle see NHANES New Content and Proposal Guidelines (cdc.gov).
    (5) Qualification: Provide a brief description of the Principal 
Investigator's expertise in the proposed area, including publications 
in this area within the last three years. A representative sample of 
earlier publications may be listed if this section does not exceed two 
pages.
    (6) Period of Performance: Specify the project time period. 
Substantial progress must be made in the first year that samples have 
been obtained, and the project should be completed within a reasonable 
time period. Please discuss the approximate time the investigator 
expects this project will take to complete the project. The NCHS 
Project Officer must be consulted about the disposition of the samples. 
At the end of the project period, any unused samples must be returned 
to the NHANES Specimen Repository or discarded appropriately.
    (7) Funding: The source and status of the funding to perform the 
requested laboratory analysis should be included. Investigators will be 
responsible for the cost of processing and shipping the samples. The 
cost per sample is $15.00. The basis for the cost structure is in the 
last section of this document. Payment for the samples will be 
collected before the samples are released.

Submission of Proposals

    Proposals can be submitted in MS Word format by Email to: 
[email protected]v.

Project Timeframes

     Submitting Proposals: Can be submitted on an ongoing 
basis.
     Scientific Review Date (NHANES Technical Panel): Within 
one month of proposal submission.
     Scientific Review Date (NCHS Human Subjects, 
Confidentiality and ERB): Within two months of Technical Panel proposal 
acceptance.
     Anticipated distribution of samples: One month after ERB 
approval and after all Interagency Agreements or Material Transfer 
Agreements are signed, and fees are paid.

Approved Proposals

    Approved projects will be provided samples after receipt of a 
signed Materials Transfer Agreement (MTA) and a check (written to The 
Centers for Disease Control and Prevention) for the cost of the 
samples, or for Federal Government proposals, a signed Interagency 
Agreement (IAA). All laboratory results obtained from the samples must 
be sent back to NCHS to be linked to the NHANES variables requested by 
the investigator and that are needed to perform a quality control 
review of the data. The results data files will undergo disclosure 
review by the NCHS Disclosure Review Board or NCHS Confidentiality 
Officer or designee before the linked data are sent to the investigator 
for quality control review. Once approved by disclosure review and 
after the investigator has signed the Data Sharing Agreement or a 
Designated Agent Agreement (respectively ``Agreement''), the linked 
data file will be sent to the investigator for use pursuant to the 
terms of the relevant agreement. The quality control review must take 
place within 60 days and the return of the data to NCHS within the next 
30 days so these data may be released to the public.

Agency Agreement

    A formal signed agreement in the form of an MTA or an IAA with 
investigators who have projects approved will be completed before the 
release of the samples to the investigator. This agreement will contain 
the conditions for use of the samples as stated in this Federal 
Register Notice and as agreed upon by the investigators and CDC.

[[Page 44370]]

Continuations

    A brief progress report will be submitted annually to NHANES. This 
report should describe work completed and timeline to project 
completion. If five years have elapsed since the initial approval of 
the protocol by the NCHS ERB a more detailed plan and timeline to 
complete the study will be required by NHANES. If at any time during 
the project a new investigator(s) are added or the Principal 
Investigator has changed, the NHANES Serum/plasma/urine Project Officer 
must be notified.

Disposition of Results and Samples

    No samples provided can be used for any purpose other than those 
specifically requested in the proposal and approved by the NHANES 
Technical Panel and the NCHS ERB. No samples can be shared with others, 
including other investigators, unless specified in the proposal and so 
approved by the NHANES Technical Panel and the NCHS ERB. Any unused 
samples must be returned to the NHANES Serum, Plasma and Urine 
Repository or disposed of, after NHANES approval, upon completion of 
the approved project. The results, once returned to NCHS, will be part 
of the public domain. The investigator will have 60 days for quality 
control review of the data before public release by NHANES.

Cost Schedule for Providing NHANES Samples

    There is a nominal processing fee of $15.00 for each sample 
received from an NHANES Serum, Plasma and Urine Repository. If the 
investigator requests to use the samples for another project after the 
completion of the initial project, the additional cost will be $5.50 
per sample 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 samples. 
The costs include the collection, processing, storage, and retrieval of 
the samples along with the review of proposals and the preparation of 
the data files. The costs listed are for the recurring laboratory 
materials to dispense and prepare the samples during collection and for 
shipping. The costs for the NHANES repository include long term storage 
(including inventory management and materials and equipment) and 
accessioning of samples and pulling samples from the freezer 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.

             Elements of the Fee for NHANES Biologic Samples
------------------------------------------------------------------------
                                                                Cost per
                         Cost factors                             vial
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Material and Equipment.......................................      $3.42
Processing the samples (Receiving, handling, and shipping)...       2.58
Inventory management.........................................       1.80
Administrative, management of the proposal process...........       1.65
Preparation of data files....................................       3.85
                                                              ----------
  Subtotal...................................................      13.30
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CDC Support (5%).............................................       0.67
                                                              ----------
  Subtotal...................................................      13.97
NCHS Support (7.50%).........................................       1.05
                                                              ----------
  Total......................................................    * 15.00
------------------------------------------------------------------------
* Total is rounded down from $15.02.

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

    Dated: August 9, 2021.
Sandra Cashman,
Executive Secretary, Centers for Disease Control and Prevention.
[FR Doc. 2021-17265 Filed 8-11-21; 8:45 am]
BILLING CODE 4163-18-P