Request for Information (RFI): Proposed Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (GWAS), 51629-51631 [E6-14416]

Agencies

• DEPARTMENT OF HEALTH AND HUMAN SERVICES
• National Institutes of Health

[Federal Register Volume 71, Number 168 (Wednesday, August 30, 2006)]
[Notices]
[Pages 51629-51631]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E6-14416]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Request for Information (RFI): Proposed Policy for Sharing of 
Data Obtained in NIH Supported or Conducted Genome-Wide Association 
Studies (GWAS)

ACTION: Notice.

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SUMMARY: The NIH is seeking comments regarding a proposed policy for 
NIH supported or conducted Genome-Wide Association Studies (GWAS). A 
genome-wide association study is currently defined as any study of 
genetic variation across the entire human genome that is designed to 
identify genetic associations with observable traits (such as blood 
pressure or weight), or the presence or absence of a disease or 
condition. The proposed policy addresses (1) data sharing procedures, 
(2) data access principles, (3) intellectual property and (4) issues 
regarding the protection of research participants through all phases of 
GWAS. Many of the principles contained in the policy reflect and extend 
existing NIH polices (e.g., the 2003 data sharing policy \1\) and other 
recent NIH discussions.\2\
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    \1\ The 2003 NIH Data Sharing Policy applies to investigators 
seeking $500,000 or more in direct costs in any year (https://
grants2.nih.gov/grants/policy/data_sharing/data_sharing_
guidance.htm).
    \2\ Request for Information on Modifications to the NHLBI Policy 
for Distribution of Data from Clinical Trials and Epidemiology 
Studies (https://www.nhlbi.nih.gov/funding/policies/rfi-genome.htm), 
2006.

DATES: Reponses must be received by October 31, 2006 in order to ensure 
that the NIH will be able to consider the comments when developing new 
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policies.

FOR FURTHER INFORMATION CONTACT: Inquiries will be accepted at: https://
grants.nih.gov/grants/guide/rfi_files/NOT-OD-06-094_rfi_add.htm or 
GWAS@nih.gov. Comments can be mailed to NIH GWAS RFI Comments, National 
Institutes of Health, Office of Extramural Research, 6705 Rockledge 
Drive, Room 350, Bethesda, MD 20892-7963.

SUPPLEMENTARY INFORMATION:

Background

    The NIH is interested in advancing GWAS to identify common genetic 
factors that influence health and disease. Whole genome information, 
when combined with clinical and other phenotypic data, offers the 
potential for increased understanding of basic biological processes 
affecting human health, improvement in the prediction of disease and 
patient care, and ultimately the realization of the promise of 
personalized medicine. In addition, rapid advances in understanding the 
patterns of human genetic variation and maturing high-throughput, cost-
effective methods for genotyping are providing powerful research tools 
for identifying genetic variants that contribute to health and disease. 
For these reasons, the NIH announced this spring that it has planned 
to: (1) Update the NIH data sharing policy for research applications 
involving GWAS data; (2) initiate a public consultation process to 
inform policy development activities; and (3) track GWAS applications 
and awards at a central level (see https://grants.nih.gov/grants/guide/
notice-files/NOT-OD-06-071.html). This RFI serves as the first step in 
the public consultation process referenced in the May 15, 2006 Notice.
    Protecting Research Participants. The potential for public benefit 
to be achieved through sharing GWAS data is significant. However, 
genotypic and phenotypic information generated about individuals, such 
as data related to the presence or risk of developing particular 
diseases or conditions, and information regarding paternity or 
ancestry, may be sensitive and substantial. Therefore, it is critically 
important that the privacy and confidentiality of the participants be 
protected. Risks to individuals, groups, or communities should be 
carefully balanced with potential benefits of the knowledge to be 
gained through GWAS. The nature of GWAS information about participants 
and the broad data distribution goals of the NIH GWAS data repository 
highlight the importance of the informed consent process to this 
research. In order to protect research participants, the NIH will 
establish mechanisms to oversee the repository and monitor GWAS data 
use practices.
    The NIH recognizes that there are evolving scientific, ethical and 
societal issues relevant to this proposed policy and will revisit and 
revise the policy as appropriate.

Proposed Policy for Genome-Wide Association Studies (GWAS)

Principles

    Consistent with both the NIH mission to improve public health 
through research and its longstanding legislative mandate to make 
available to the public the results of the research activities that it 
supports and conducts, the NIH believes that the full value of GWAS to 
the public can be realized only if the genotype and phenotype datasets 
are made available as rapidly as possible to a wide range of scientific 
investigators. Rapid and broad data access is particularly important 
for GWAS because of the significant resources involved; the challenges 
of analyzing large datasets; and the extraordinary opportunities for 
making comparisons across multiple studies.
    Protection of research participants is a fundamental principle 
underlying biomedical research. The NIH is committed to responsible 
stewardship of data throughout the research process, which is essential 
to protecting the interests of study participants and to maintaining 
public trust in biomedical research.

Applicability

    This draft policy is proposed to apply to active research 
applications identified by applicants or NIH staff as GWAS per NOT-OD-
06-071.

Data Management

    Data Repository. To facilitate broad and consistent access to NIH-
supported GWAS datasets, the NIH proposes the development of a central 
GWAS data repository, at the NIH (National Center for Biotechnology 
Information [NCBI], National Library of Medicine). The repository will 
provide a single point of

[[Page 51630]]

access to basic information about NIH-supported GWAS and to available 
genotype-phenotype datasets for GWAS. Although the NIH envisions that 
access to all NIH-supported GWAS datasets will be possible through this 
repository, it does not intend this repository to become the exclusive 
source of these data. The repository will also accept GWAS datasets 
contributed from other sources.
    Data Submission. All investigators who receive NIH support to 
conduct genome-wide analysis of genetic variation in a study population 
are expected to submit to the GWAS data repository descriptive 
information about their studies for inclusion in an open access portion 
of the GWAS data repository. This information should include the 
following:
     The protocol,
     Questionnaires,
     Study manuals,
     Variables measured, and
     Other supporting documentation.
    In addition, the NIH strongly encourages the submission of curated 
and coded phenotype, exposure, genotype, and pedigree data, as 
appropriate, to the GWAS data repository as soon as quality control 
procedures have been completed at the local institution. These detailed 
data will be made available through a controlled access process 
according to the GWAS Data Access procedures (described below). 
Investigators who elect to submit their GWAS data to additional data 
repositories or networks should verify that appropriate data security, 
confidentiality, and privacy measures are in place for the protection 
of GWAS participants.
    In order to minimize the risks to study participants, data will be 
submitted to the GWAS data repository without identifiable information 
and using a random, unique code. Keys to codes will be held by 
submitting institutions. Submissions of GWAS data should be accompanied 
by a written certification stating that the identities of research 
participants will not be disclosed to the GWAS data repository or to 
secondary users of the coded data without appropriate institutional 
approvals. Therefore, research participants should not expect the 
return of individual research results derived from analyses of 
submitted data.
    All submissions to the GWAS data repository should be accompanied 
by:
     A certification by the responsible IRB that they have 
reviewed and approved the submission to the GWAS data repository, 
noting specifically that:
    [cir] Inclusion in the GWAS data repository and subsequent sharing 
for appropriate research purposes is consistent with the initial 
informed consent process of study participants from whom the data were 
obtained; and
    [cir] Identifying any uses of the data that are specifically 
excluded within the informed consent provided by study participants, 
which will be noted in the database; and
     A statement from the institution from which data are 
contributed that submission of the data is in accord with all 
applicable laws and regulations.\3\
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    \3\ Applicable Federal regulations may include HHS human 
subjects regulations (45 CFR Part 46), FDA human subjects 
regulations (21 CFR Parts 50 and 56), and the Health Insurance 
Portability and Accountability Act Privacy Rule (45 CFR Part 160 and 
Part 164, Subparts A and E).
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    Data Access. The basic descriptive information submitted to the 
GWAS data repository for each NIH-conducted or supported GWAS will be 
available to the public through the GWAS data repository. Access to the 
genotype and phenotype datasets submitted and stored in the GWAS data 
repository along with pre-computed analyses (such as simple genotype-
phenotype associations and a listing of all variants known to be in 
linkage disequilibrium \4\ with variants showing significant 
association with a phenotype or trait) will be provided for research 
purposes through an NIH Data Access Committee (DAC). NIH anticipates 
that individual DACs may be established based on programmatic areas of 
interest and the relevant needs for technical and ethics expertise. All 
DACs will operate through common principles and under similar 
mechanisms to ensure the consistency and transparency of the GWAS data 
access process.
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    \4\ Linkage disequilibrium information will be based on data 
from the International HapMap Project (https://www.hapmap.org).
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    Investigators seeking data from the GWAS data repository will be 
asked to submit a Data Use Certification that is co-signed by the 
designated Institutional Official, for approval by the appropriate NIH 
DAC. Data Use Certifications should include a brief description of the 
proposed research use of the requested GWAS dataset(s). Within a Data 
Use Certification, investigators will stipulate that they will:
     Use the data only for the approved research use;
     Protect data confidentiality;
     Follow all applicable laws and any local institutional 
policies and procedures for handling GWAS data;
     Not attempt to identify individual participants from whom 
data within a dataset were obtained;
     Not sell or share any of the data elements from datasets 
obtained from the GWAS data repository with third parties; and
     Provide annual progress reports on research.
    Access to GWAS datasets through the GWAS data repository will be 
approved by DACs following: (1) The completion of the Data Use 
Certification; and (2) confirmation that the proposed research use is 
consistent with any constraints identified by the institutions that 
submitted the dataset to the GWAS data repository.

Publication

    The NIH expects that for a defined period of time following the 
release of a given genotype-phenotype dataset through the GWAS data 
repository (including the pre-computed analyses of the data), the 
investigators who contributed the data to the GWAS data repository 
should retain the exclusive right to publish analyses of the dataset. 
During this period of exclusivity, the NIH may grant access to other 
investigators, who may analyze the data, but are expected not to 
publish their analyses or conclusions during this period. This period 
of exclusivity is presently anticipated to be nine months from the date 
that the GWAS dataset is made available for access through the GWAS 
data repository, although a shorter period of exclusivity may be 
requested by the NIH funding Institute or Center. Contributing 
investigators are encouraged to shorten any such period of publication 
exclusivity at their own discretion. Following the expiration of the 
exclusive publication period for a given GWAS dataset, NIH expects that 
any investigator with access to the data may submit publications for 
any purpose consistent with the practices and policies of their 
institution and the NIH.
    The NIH also expects that all investigators who access GWAS 
datasets will acknowledge the Contributing Investigator(s) who 
conducted the original study, and the funding organization(s) that 
supported the work in all resulting oral or written presentations, 
disclosures, or publications of the analyses.

Intellectual Property

    It is the hope of the NIH that genotype-phenotype associations 
identified through NIH-supported and maintained GWAS datasets and their 
obvious implications will remain available to all investigators, 
unencumbered by intellectual property claims. The NIH discourages 
premature claims on pre-competitive information that may impede 
research, though it encourages patenting of technology

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suitable for subsequent private investment that may lead to the 
development of products that address public needs.
    The NIH will provide approved GWAS data users with information 
regarding any significant associations within GWAS genotype-phenotype 
data and other pre-computed analyses (described under the Data Access 
section on page 4) as a component of the GWAS datasets distributed 
through the GWAS data repository.
    The NIH expects that NIH-supported genotype-phenotype data made 
available through the GWAS data repository and all conclusions derived 
directly from them will remain freely available, without any licensing 
requirements, for uses such as, but not necessarily limited to, markers 
for developing assays and guides for identifying new potential targets 
for drugs, therapeutics, and diagnostics. The intent is to discourage 
the use of patents that would prevent the use of or block access to any 
genotype-phenotype data developed with NIH support. The NIH encourages 
broad use of NIH-supported genotype-phenotype data that is consistent 
with a responsible approach to management of intellectual property 
derived from downstream discoveries as outlined in NIH's Best Practices 
for the Licensing of Genomic Inventions (https://www.ott.nih.gov/policy/
genomic_invention.html) and its Research Tools Policy (https://
ott.od.nih.gov/policy/research_tool.html).
    The filing of patent applications and/or the enforcement of 
resultant patents in a manner that might restrict use of NIH-supported 
genotype-phenotype data could substantially diminish the utilization of 
information and the potential public benefit they could provide. 
Approved Users and their institutions, through the execution of an NIH 
Data Use Certification, will acknowledge the goal of ensuring the 
greatest possible public benefit from NIH-supported GWAS.

Expectations for Investigators Under the Proposed Policy

    Although the detailed expectations are enumerated in the individual 
sections of this proposed policy, they are summarized as follows:
    Investigators submitting GWAS data will be expected to:
     Provide descriptive information about their studies;
     Submit coded genotypic and phenotypic data to the GWAS 
data repository;
     Submit certification by the responsible IRB that it has 
reviewed and approved submission to the NIH, noting any limitations on 
data use based on the relevant informed consents; and
     Submit an assurance from the responsible institution that 
all data are submitted to the NIH in accord with applicable law.
    Investigators requesting GWAS data will be expected to:
     Submit a description of the proposed research project;
     Submit a Data Use Certification co-signed by their 
sponsoring institution;
     Protect data confidentiality; and
     Submit annual progress reports detailing significant 
research findings.

Information Requested

    The goal of the proposed policy is to advance science for the 
benefit of the public through the creation of a centralized NIH GWAS 
data repository. Maximizing the availability of resources facilitates 
research and enables medical science to better address the health needs 
of people based on their individual genetic information. The NIH is 
seeking public input and advice on the overall concept of the proposed 
policy and specific feedback on the following questions:
    1. What are the potential benefits and risks associated with wide 
sharing of phenotypic and genotypic data where identifying information 
has been removed?
    2. In addition to removing personal identifying information, what 
protections are needed to minimize risks to research participants whose 
phenotypic and genotypic data are included in a centralized NIH data 
repository and shared with qualified investigators for research 
purposes?
    3. What are the advantages and disadvantages of the proposed:
    a. Centralized NIH data repository?
    b. Approach to data submission?
    c. Approach to scientific publication?
    d. Approach to intellectual property?
    4. What specific resources may investigators and institutions need 
to meet the goals of this proposed policy?

Responses

    The NIH encourages comments concerning its proposed policy to 
enhance access to GWAS data as outlined in this notice. Persons, 
groups, and organizations interested in commenting on NIH's proposed 
policy should direct their comments to the following NIH Web site: 
https://grants.nih.gov/grants/guide/rfi_files/NOT-OD-06-094_rfi_
add.htm. As an alternative, comments may be submitted by e-mail to 
GWAS@nih.gov or sent by mail to the following address: NIH GWAS RFI 
Comments, National Institutes of Health, Office of Extramural Research, 
6705 Rockledge Drive, Room 350, Bethesda, MD 20892-7963.

    Dated: August 24, 2006.
Sally Rockey,
Acting Deputy Director for Extramural Research, National Institutes of 
Health.
 [FR Doc. E6-14416 Filed 8-29-06; 8:45 am]
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