[Federal Register: August 28, 2007 (Volume 72, Number 166)]
[Notices]
[Page 49290-49297]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28au07-117]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Policy for Sharing of Data Obtained in NIH Supported or Conducted
Genome-Wide Association Studies (GWAS)
AGENCY: National Institutes of Health, HHS.
ACTION: Notice.
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Background
The NIH is interested in advancing genome-wide association studies
(GWAS) to identify common genetic factors that influence health and
disease. For the purposes of this policy, a genome-wide association
study is 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.\1\ Whole genome information, when
combined with clinical and other phenotype data, offers the potential
for increased understanding of basic biological processes affecting
human health, improvement in the prediction of disease and patient
care, and
[[Page 49291]]
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.
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\1\ To meet the definition of a GWAS, the density of genetic
markers and the extent of linkage disequilibrium should be
sufficient to capture (by the r\2\ parameter) a large proportion of
the common variation in the genome of the population under study,
and the number of samples (in a case-control or trio design) should
provide sufficient power to detect variants of modest effect.
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For these reasons, the NIH announced in May 2006 that it planned
to: (1) Update NIH data sharing policies 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 (NOT-OD-06-071--http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-071.html
). A call for public
comments on a proposed GWAS policy was issued on August 30, 2006 (NOT-
OD-06-094--http://grants.nih.gov/grants/guide/notice-files/NOT-OD-06-094.html
). Between August 30 and November 30, 2006, the NIH solicited
public comments from a range of public sectors (see Preamble below).
Following the comment period, NIH convened a Town Hall Meeting in
Bethesda, Maryland, on December 14, 2006, to provide an opportunity for
direct interaction with interested stakeholders on the important policy
questions raised through the proposed policy (NOT-OD-06-022--http://grants.nih.gov/grants/guide/notice-files/NOT-OD-06-022.html
).
This Notice provides the NIH response to the public comments
received during the public consultation activities and presents the
revised GWAS policy developed by the NIH in response to the feedback
received and further internal development of the issues. The 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 existing NIH polices and
other NIH discussions.
The goal of the 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.
Protecting Research Participants
The potential for public benefit to be achieved through sharing
GWAS data is significant. However, genotype and phenotype 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. Therefore,
protecting the privacy of the research participants and the
confidentiality of their data is critically important. Risks to
individuals, groups, or communities should be balanced carefully with
potential benefits of the knowledge to be gained through GWAS. The
sensitive 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.
The NIH recognizes that scientific, ethical and societal issues
relevant to this policy are evolving, and the agency has established
on-going mechanisms to oversee GWAS policy implementation across the
agency and to monitor whole genome association data use practices. The
NIH will revisit and revise the policy and related practices as
appropriate.
Preamble: Summary of Public Comments on Proposed Policy
On August 30, 2006, the NIH published the Proposed Policy for
Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide
Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-06-094.html
) for public comment in the Federal Register
and the NIH Guide for Grants and Contracts. The comment period ended
with a Town Hall meeting held in Bethesda, Maryland on December 14,
2006, that was attended by a total of 374 people (on-site and via
webcast).
Overall the NIH received 196 written comments from professional
societies, patient advocacy groups, privacy groups, individual
scientists, and private citizens. The comments reflected a variety of
interests and perspectives. In developing policies, the NIH strives to
be respectful of the diversity of individual and group interests,
incorporating appropriate protections while promoting maximum public
benefit from the research it sponsors. The NIH GWAS policy and its
implementation are expected to evolve in response to advances in
scientific knowledge, available technologies, and the legal and ethical
issues they raise.
I. Rationale for a Centralized Data Repository
Respondents asked for clarification of the rationale for creation
of a central data repository instead of distributed repositories under
the control of individual (and non-governmental) institutions and
investigators. Concerns expressed about a central data repository
included, for example, the resources required to maintain it and the
extent to which it would duplicate efforts and resources already
invested by multiple institutions.
The advantages and limitations of central versus distributed data
repositories have been discussed extensively at the NIH. From a
scientific standpoint, a central repository offers a number of
important advantages: Tighter and more consistent control over the
standards and quality of the genotype and phenotype data included; the
ability to standardize and update terminology and format as technology
and methodology improve; consistent, defined and transparent security
and standards for access to data; a long-term commitment to maintenance
of data after studies have been completed; a common point of entry for
all investigators who use the data; a consistent and defined approach
to removal of data in the event of withdrawal of participant consent;
facilitation of meta-analyses and analyses that use data from multiple
studies; and the ability to implement consistent participant
protections at the level of data submission and data access. Individual
investigators and many institutions may lack sufficient resources to
ensure consistency and quality control, or a long-term commitment to
data storage and access. One of the potential disadvantages of a
central repository residing at NIH is that the data may be accessible
through the Federal Freedom of Information Act (FOIA), unless they are
exempt from release under one of the FOIA exemptions. This is further
discussed in the Protection of Research Participants section below.
As clinical and genomics research progresses, genotype and
phenotype data are being collected into databases maintained by a
variety of investigators, studies, and institutions. The NIH is
concerned that the present situation may provide less consistent
standards for the protection of research participants, data quality,
and data access than would a central repository. However, the NIH
recognizes that other databases will be designed to achieve different
scientific aims or to integrate different analytic capacities, and the
NIH GWAS policy is not intended to constrain the development of such
databases or to curtail the deposition of NIH-supported GWAS data into
other databases (as may be appropriate or required for some research
programs). Among the on-going charges to the trans-NIH Technical
Standards Steering
[[Page 49292]]
Committee established through the GWAS governance structure (see
Oversight and Governance section below) will be explicit consideration
of the evolving technical capacities and interoperability needed to
facilitate the submission of data into the NIH GWAS data repository \2\
through other major database systems (e.g., the NCI caBIG network).
This committee also will provide a forum for inter-IC coordination of
data structures and standards to maintain interoperability of NIH
databases.
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\2\ Currently named the NIH database of Genotypes and Phenotypes
(dbGaP) (http://www.ncbi.nlm.nih.gov/entrez/query/Gap/gap_tmpl/about.html
).
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II. Protection of Research Participants
Non-Research Use of Data
Respondents noted that data held by the Government are subject to
the FOIA, and thus could be obtained outside of the Controlled Access
data request process described in the GWAS policy. Respondents
expressed concern that data could be obtained for non-research purposes
(e.g., by law enforcement agencies, employers, or insurance companies)
or for purposes beyond the scope of the research uses envisioned within
the GWAS policy.
As an agency of the Federal Government, the NIH is required to
release Government records in response to a request under the FOIA,
unless they are exempt from release under one of the FOIA exemptions.
Although the NIH-held data will be coded and the NIH will not hold
direct identifiers to individuals within the NIH GWAS data repository,
the agency recognizes the personal and potentially sensitive nature of
the genotype-phenotype data. Further, the NIH takes the position that
technologies available within the public domain today, and
technological advances expected over the next few years, make the
identification of specific individuals from raw genotype-phenotype data
feasible and increasingly straightforward.
The agency believes that release of unredacted GWAS datasets in
response to a FOIA request would constitute an unreasonable invasion of
personal privacy under FOIA Exemption 6, 5 U.S.C. 552(b)(6). Therefore,
among the safeguards that the NIH foresees using to preserve the
privacy of research participants and confidentiality of genomic data is
the redaction of individual-level genotype and phenotype data from
disclosures made in response to FOIA requests and the denial of
requests for unredacted datasets.
In addition, the NIH acknowledges that legitimate requests for
access to data made by law enforcement offices to the NIH may be
fulfilled. The NIH will not possess direct identifiers within the NIH
GWAS data repository, nor will the NIH have access to the link between
the data keycode and the identifiable information that may reside with
the primary investigators and institutions for particular studies. The
release of identifiable information may be protected from compelled
disclosure by the primary investigator's institution if a Certificate
of Confidentiality is or was obtained for the original study. Within
the final GWAS policy, the NIH explicitly encourages investigators to
consider the potential appropriateness of obtaining a Certificate of
Confidentiality as an added measure of protection against future
compelled disclosure of identities for studies planning to collect
genome-wide association data.
Stigmatization
Respondents commented that some data to be included in the
repository may be highly sensitive because they may suggest the
existence either of individually identifiable or socially undesirable
traits. These data have implications for both participants and family
members.
Tools for analysis of genomic data increasingly are able to make
inferences about some individual traits (e.g., height, weight, skin and
hair and eye color) and to identify predilections for characteristics
(e.g., risk of developing some diseases) and behaviors with social
stigma. In recognition of these risks, the NIH policy includes steps to
protect the interests and privacy concerns of individuals, families and
identifiable groups who participate in GWAS research. The NIH is asking
institutions submitting GWAS datasets to certify that an Institutional
Review Board (IRB) and/or Privacy Board (as applicable) has considered
such risks and that investigators have stripped the data of all
identifiers before the data are submitted. The NIH Data Access
Committees (DACs) will approve access only for research uses that are
consistent with an individual's consent as defined by the submitting
institution. In addition, in the event that requests raise questions or
concerns related to privacy and confidentiality, risks to populations
or groups, or other relevant topics, the DACs will consult with other
experts as appropriate.
Informed Consent
Respondents asked for clarification regarding appropriate informed
consent processes and consent documentation for individuals
participating in studies for which data are to be submitted to the NIH
GWAS data repository. Concern was raised that participants may not be
aware of the potential privacy risks associated with placement of their
genotype and phenotype data in a central repository at the NIH.
Respondents also commented that adequate consent for data sharing
requires participants to understand both the risks and potential
benefits of the proposed sharing. Key stakeholders in these
considerations are: Research participants (both those who have
participated in on-going or prior studies for which GWAS were not
anticipated and those who may participate in prospective GWAS);
investigators developing informed consent processes; institutions
approving the submission of datasets to the NIH GWAS data repository;
and IRBs asked to review studies proposing genome-wide association
analysis. Respondents commented that additional institutional resources
are likely to be required if additional consent is needed for data
sharing.
As noted elsewhere and reflected in the GWAS oversight structure
established to manage implementation of the GWAS policy (see Oversight
and Governance section below), the NIH recognizes that the ethical
considerations relevant to GWAS data sharing are complex and dynamic.
Therefore, the NIH is developing informational materials as a resource
for IRBs and institutions for their consideration of the issues
relevant to reviewing and approving individual studies proposing data
submission to the NIH GWAS data repository. The NIH intends to continue
to engage the Office for Human Research Protections, the research
community, and the public to explore the participant protection issues
related to GWAS and to identify best practices for the consideration
and risk-benefit analysis of genotype and phenotype data sharing under
this policy. These efforts will include discussion of the optimal
methods for communicating with participants about relevant issues
through the informed consent process for prospective studies, and
discussion of issues to consider in the institutional review of consent
materials for use of existing samples or data proposed for GWAS.
Participant interests relevant to GWAS data sharing extend beyond
individual participants to families, communities, and their respective
cultural sensitivities. The NIH believes that institutional
deliberations regarding data submission
[[Page 49293]]
to the NIH GWAS data repository should include these broader interests.
Further, especially complex issues exist with regard to GWAS where
participant consent has been provided by proxy (e.g., pediatric
research or some studies involving mental health disorders). Discussion
of this topic will be included in the informational materials \3\ that
the NIH is developing for submitting institutions and IRBs asked to
review proposed GWAS.
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\3\ The NIH anticipates releasing additional GWAS implementation
documents, including a Points to Consider document on informed
consent issues related to the submission of data to the repository.
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The GWAS policy applies to genome-wide association research
utilizing genetic materials and data collected both prospectively and
retrospectively. For prospective studies, in which GWAS are conceived
within the study designs at the time research participants provide
their consent, the NIH expects specific discussion within the informed
consent process and documentation that participants' genotype and
phenotype data will be shared for research purposes through the NIH
GWAS data repository. For retrospective studies performed using
existing genetic materials and previously collected data, the NIH
anticipates considerable variation in the extent to which data sharing
and future genetic research have been addressed within the informed
consent documents. As described in the policy, the submitting
institution will determine whether a study is appropriate for
submission to the NIH GWAS data repository (including an IRB and/or
Privacy Board review of specific study elements, such as participant
consent). The NIH anticipates that a number of GWAS proposing to
include pre-existing data or samples may require additional consent of
the research participants. The NIH may give programmatic consideration
to requests for funds or other resources needed to conduct additional
participant consent when appropriate.
In the event that participants withdraw consent for sharing of
their individual-level genotype and phenotype data through the NIH GWAS
data repository, the submitting institution will be responsible for
alerting the NIH GWAS data repository and requesting that the specific
record be removed from future data distributions. However, data that
have been distributed to researchers will not be retracted.
Return of Results
Respondents asked for clarification of plans for return of results
to study participants.
The NIH does not anticipate that participants will be able to
obtain individual results of secondary analyses on data obtained from
their participation in primary studies. Because the NIH GWAS data
repository and secondary data users will not have access to identifying
information or to the link to the keycode within the data, neither will
be able to return individual results directly to subjects. Secondary
investigators may share their findings with primary investigators, who
may determine whether it is appropriate to return individual or
aggregate research results to participants whose health may be
affected, following established institutional procedures (e.g., IRB
approval) and specific parameters defined within the original study.
Oversight and Governance of the NIH GWAS Data Repository, Submission
and Access
Some respondents commented on the importance of adequate oversight
of policies for data submission and access, and on the details of the
repository. A need for oversight of the quality control measures for
genotype and phenotype data and of the security measures for the
repository was noted by many respondents. Some respondents commented on
the importance of the policies established by the Data Access
Committees, and their function within the Institutes and Centers.
The NIH has developed a governance structure for GWAS that provides
oversight tailored to the specific role involved. The NIH Director will
oversee the GWAS policy and its implementation. In carrying out this
responsibility, the NIH Director will be informed by a Senior Oversight
Committee composed of Institute and Center (IC) Directors and
appropriate leadership from within the Office of the Director. The
Senior Oversight Committee will be responsible for the on-going
management and stewardship of GWAS policy and operating implementation
procedures across ICs. Reporting to the Senior Oversight Committee will
be two Steering Committees charged with the implementation,
communication, and development of specific procedures related to the
conduct, submission and data release practices for GWAS supported by
the NIH. One of these groups, the Research Participant Protection and
Data Management Steering Committee, will include among its members the
chairs of all Data Access Committees at the NIH as well as appropriate
staff from NIH policy and oversight offices (e.g., the Office of
Science Policy and the Office of Human Subjects Research). This
committee will work to promote consistent and robust participant
protections across relevant NIH programs. The second group, the
Technical Standards Steering Committee, will include membership from
scientific programs across the NIH as well as staff from the National
Center for Biotechnology Information. This committee will focus on the
challenges and needs associated with building and maintaining the NIH
GWAS data repository and on formulating or stimulating the
consideration of data standards (for genotype or phenotype data) where
appropriate. Critical input from individual genome-wide association
research programs and studies will be provided to the two Steering
Committees through the ICs' Data Access Committees or other project
oversight bodies created for specific studies, e.g., community
representative groups, scientific advisory boards.
In order to maintain GWAS policy consistent with evolving
technological and ethical considerations, the NIH Director will solicit
recommendations on the policy from external experts representing public
and scientific stakeholders through the Advisory Committee to the
Director.
III. Scientific Publication
Some respondents commented on the considerable logistical
difficulties posed by limiting the period of publication exclusivity,
particularly considering the complexity of many of the studies and the
lag time between submission and publication of peer-reviewed scientific
papers. Some respondents were concerned that submitting investigators
would not receive appropriate credit for their work and would have
insufficient control over use of their data. Concern was expressed
about enforcing compliance with publication policies. Some respondents
commented that the limited period of exclusivity could stimulate a rush
to publish initial analyses prematurely, deterring subsequent studies
and reducing the overall quality of the reports.
The NIH initially proposed that GWAS datasets be made available as
soon as appropriate quality control measures (as defined for a given
NIH program) were complete and that a 9-month period of exclusivity
would exist for primary investigators to submit analyses of GWAS
datasets for publication. The NIH believes that an extended period of
exclusivity would
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undermine the potential benefits of data sharing. However, in response
to concerns raised through the public comment process, the NIH has
lengthened this exclusivity period to 12 months in the final policy.
The publication exclusivity period will commence on the date that a
GWAS dataset is first made available through the NIH GWAS data
repository, and the expiration date of this time period will be
featured prominently in all descriptions and overviews of the dataset
provided through both the public and controlled access pathways of the
NIH GWAS data repository. The policy now is explicit on the inclusion
within this exclusivity period of electronic and other means of
information dissemination beyond peer-reviewed publications. As part of
an overarching desire for transparency in the use of GWAS datasets, the
names, institutional affiliations, and Data Access Committee-approved
research uses for all GWAS data users will be available to the public
within the NIH GWAS data repository. GWAS data users will be encouraged
to collaborate with the primary investigators for GWAS as appropriate.
The period of exclusivity is consistent with existing practices for
other genome-wide association programs already available or in the
pipeline for deposition into the NIH GWAS data repository, and is
intended only as an upper limit as some NIH programs may stipulate
shorter (or no) publication exclusivity timelines. The NIH anticipates
that over time investigators will become more comfortable with the GWAS
data sharing policy as the benefits of greater research access to the
data are realized.
IV. Intellectual Property
Respondents raised concerns that the policy might diminish the
intellectual property rights of the submitting investigators, as well
as their ability to obtain patents. Some respondents questioned whether
the proposed policy text is a violation of the Bayh-Dole Act.
The NIH believes that the intellectual property section of the
policy presents no conflict with, or infringement upon, rights granted
by the Bayh-Dole Act or any other federally-created intellectual
property rights. Funding recipients are still able to elect title to
any inventions or discoveries developed under the respective federal
funding agreements that are or may be patentable, consistent with the
Bayh-Dole Act and NIH policies. The NIH expects that intellectual
property issues or questions that may occur will be resolvable through
appropriate negotiations under the rubrics provided previously in NIH
guidance to the research community within the Research Tools Policy
(http://ott.od.nih.gov/policy/research_tool.html) and the Best Practices for the Licensing of Genomic Inventions (http://
http://www.ott.nih.gov/policy/genomic_invention.html). The NIH encourages
development of new diagnostics, therapeutics, or other interventions
building on basic discoveries, and believes they will be enabled
through the NIH GWAS data repository. The NIH anticipates that
downstream technology development opportunities will increase as a
result of broad research access to genotype-phenotype associations
provided through the GWAS policy. The NIH has engaged in informal
discussions with academic and private sector experts in intellectual
property; these interactions, as well as formal responses received from
stakeholders through the GWAS public consultation process, have
suggested that the GWAS policy is consistent with existing practices
and can be expected to better promote the development of exciting new
discoveries for the public benefit.
Policy for Genome-Wide Association Studies (GWAS)
Effective Date: January 25, 2008.
I. Principles
The NIH is interested in advancing genome-wide association studies
(GWAS) to identify common genetic factors that influence health and
disease. For the purposes of this policy, a genome-wide association
study is 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.\4\ Whole genome information, when
combined with clinical and other phenotype 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.
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\4\ To meet the definition of a GWAS, the density of genetic
markers and the extent of linkage disequilibrium should be
sufficient to capture (by the r\2\ parameter) a large proportion of
the common variation in the genome of the population under study,
and the number of samples (in a case-control or trio design) should
provide sufficient power to detect variants of modest effect.
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Consistent with the NIH mission to improve public health through
research, 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 they require; 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.
In consideration of the evolving scientific, ethical, and societal
issues related to this policy, the NIH is establishing a governance
structure for NIH GWAS activities that will:
Ensure ongoing, high-level agency oversight; and
Obtain regular input from public representatives,
including those with expertise in bioethics, privacy, data security,
and appropriate scientific and clinical disciplines; and
Revisit and revise the policy as appropriate.
II. Applicability
This NIH policy applies to:
Competing grant applications that include GWAS and are
submitted to the NIH for the January 25, 2008, and subsequent receipt
dates;
Proposals for contracts that include GWAS and are
submitted to the NIH on or after January 25, 2008; and
NIH intramural research projects that include GWAS and are
approved on or after January 25, 2008.
An application or proposal will be identified as GWAS by applicants
and/or NIH staff (see NOT-OD-06-071--http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-071.html
).
III. Data Management
Data Repository
To facilitate broad and consistent access to NIH-supported GWAS
datasets, the NIH has developed a central NIH GWAS data repository \5\
at
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the National Center for Biotechnology Information (NCBI), National
Library of Medicine. The repository will provide a single-point of
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 the repository to become the exclusive
point of data submission for these data, nor does it intend the central
database to delimit the structures or tools that may be appropriate for
other similar databases. The repository also will accept GWAS datasets
contributed from other sources.
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\5\ Currently named the NIH database of Genotypes and Phenotypes
(dbGaP) (http://www.ncbi.nlm.nih.gov/entrez/query/Gap_tmpl/about.html
).
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To ensure the security of the data held by the repository, the NCBI
will employ multiple tiers of data security (such as sequential
firewalls and independent networks) based on the content and level of
risk associated with the data. The NIH will establish and maintain
operating policies and procedures for the repository to address issues
including, but not limited to, the privacy and confidentiality of GWAS
research participants, the interests of individuals and groups, data
access procedures, and data security mechanisms. These will be reviewed
periodically by the GWAS oversight bodies.
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 NIH GWAS data repository descriptive information about
their studies for inclusion in an open access portion of the NIH GWAS
data repository. All data and information will be submitted to a high
security network within the NCBI through a secure transmission process.
Submissions 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 NIH 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 in Data Access
section 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
protection of GWAS participants. Irrespective of where the data are
submitted, researchers submitting GWAS data are encouraged to consider
whether a Certificate of Confidentiality might be appropriate for their
data as an additional safeguard with regard to involuntary disclosure
of the research participant identities. Further information about
Certificates of Confidentiality is available at the following Web site:
http://grants2.nih.gov/grants/policy/coc/.
In order to minimize risks to study participants, data submitted to
the NIH GWAS data repository will be de-identified and coded using a
random, unique code. Data should be de-identified according to the
following criteria: the identities of data subjects cannot be readily
ascertained or otherwise associated with the data by the repository
staff or secondary data users (45 CFR 46.102(f)); the 18 identifiers
enumerated at section 45 CFR 164.514(b)(2) (the HIPAA Privacy Rule) are
removed; and the submitting institution has no actual knowledge that
the remaining information could be used alone or in combination with
other information to identify the subject of the data.\6\ Keys to codes
will be held by submitting institutions. Submissions of GWAS data
should be accompanied by a written certification (detailed below)
stating that the identities of research participants will not be
disclosed to the NIH GWAS data repository. Therefore, the NIH GWAS data
repository will be unable to provide individual research results
derived from analyses of submitted data to participants. General
information regarding known publications analyzing GWAS datasets will
be made available through the repository.
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\6\ The identities of data subjects cannot be readily
ascertained or otherwise associated with the data by the repository
staff or secondary data users (Common Rule); and the following data
elements have been removed (HIPAA Privacy Rule).
1. Names.
2. All geographic subdivisions smaller than a state, including
street address, city, county, precinct, ZIP Code, and their
equivalent geographical codes, except for the initial three digits
of a ZIP Code if, according to the current publicly available data
from the Bureau of the Census: a. The geographic unit formed by
combining all ZIP Codes with the same three initial digits contains
more than 20,000 people. b. The initial three digits of a ZIP Code
for all such geographic units containing 20,000 or fewer people are
changed to 000.
3. All elements of dates (except year) for dates directly
related to an individual, including birth date, admission date,
discharge date, date of death; and all ages over 89 and all elements
of dates (including year) indicative of such age, except that such
ages and elements may be aggregated into a single category of age 90
or older.
4. Telephone numbers.
5. Facsimile numbers.
6. Electronic mail addresses.
7. Social Security numbers.
8. Medical record numbers.
9. Health plan beneficiary numbers.
10. Account numbers.
11. Certificate/license numbers.
12. Vehicle identifiers and serial numbers, including license
plate numbers.
13. Device identifiers and serial numbers.
14. Web universal resource locators (URLs).
15. Internet protocol (IP) addresses numbers.
16. Biometric identifiers, including fingerprints and
voiceprints.
17. Full-face photographic images and any comparable images.
18. Any other unique identifying number, characteristic, or
code, unless otherwise permitted by the Privacy Rule for re-
identification.
In addition, the submitting institution should have no actual
knowledge that the remaining information could be used alone or in
combination with other information to identify the individual who is
the subject of the information.
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All submissions to the NIH GWAS data repository should be
accompanied by a certification by the responsible Institutional
Official(s) of the submitting institution that they approve submission
to the NIH GWAS data repository.
The certification should assure that:
The data submission is consistent with all applicable laws
and regulations,\7\ as well as institutional policies;
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\7\ 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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The appropriate research uses of the data and the uses
that are specifically excluded by the informed consent documents are
delineated;
The identities of research participants will not be
disclosed to the NIH GWAS data repository; and
An IRB and/or Privacy Board, as applicable, reviewed and
verified that:
[cir] The submission of data to the NIH GWAS data repository and
subsequent sharing for research purposes are consistent with the
informed consent of study participants from whom the data were
obtained;
[cir] The investigator's plan for de-identifying datasets is
consistent with the standards outlined above;
[cir] It has considered the risks to individuals, their families,
and groups or populations associated with data submitted to the NIH
GWAS data repository; and
[cir] The genotype and phenotype data to be submitted were
collected in a manner consistent with 45 CFR part 46.
While the NIH encourages data sharing through this policy,
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circumstances beyond the control of investigators may preclude
submission of GWAS data to the NIH GWAS data repository. Applications
submitted to the NIH for support of GWAS in which the above
expectations for data submission cannot be met will be considered for
funding on a case-by-case basis by the appropriate IC.
Submitting investigators and their institutions may request removal
of data on individual participants from the NIH GWAS data repository in
the event that a research participant withdraws his or her consent.
However, data that have been distributed for approved research use will
not be retrieved.
Data Access
The basic descriptive and aggregate summary information submitted
to the NIH GWAS data repository for each NIH-supported or conducted
GWAS will be available publicly through the NIH GWAS data repository.
Access to the genotype and phenotype datasets submitted and stored in
the NIH GWAS data repository, along with appropriate automated
calculations (e.g., quality control measures, simple genotype-phenotype
associations, or a listing of all variants known to be in linkage
disequilibrium \8\ with variants measured in the genotype), will be
provided for research purposes through an NIH Data Access Committee
(DAC). Membership of the DACs will include Federal staff with relevant
expertise in areas such as the relevant particular scientific
disciplines, research participant protection, and privacy. The 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 according to common principles
and follow similar procedures to ensure the consistency and
transparency of the GWAS data access process.
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\8\ Linkage disequilibrium information will be based on data
from the International HapMap Project (http://www.hapmap.org/).
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Investigators and institutions seeking data from the NIH GWAS data
repository will be expected to meet data security measures (such as
physical security, information technology security, and user training)
and will be asked to submit a data access request, including a Data Use
Certification, that is co-signed by the investigator and the designated
Institutional Official(s). Data access requests should include a brief
description of the proposed research use of the requested GWAS
dataset(s). Within a Data Use Certification investigators will agree,
among other things,\9\ to:
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\9\ Investigators requesting access to GWAS datasets who also
have access to identifying information for the individuals within
the dataset will require IRB approval.
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Use the data only for the approved research;
Protect data confidentiality;
Follow appropriate data security protections;
Follow all applicable laws, regulations and 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 any of the data elements from datasets obtained
from the NIH GWAS data repository;
Not share with individuals other than those listed in the
request any of the data elements from datasets obtained from the NIH
GWAS data repository;
Agree to the listing of a summary of approved research
uses within the NIH GWAS data repository along with his or her name and
organizational affiliation;
Agree to report, in real time, violations of the GWAS
policy to the appropriate DAC;
Acknowledge the GWAS policy with regard to publication and
intellectual property; and
Provide annual progress reports on research using the GWAS
dataset.
Data Access Committees or their designees will review requests for
access to determine whether the proposed use of the dataset is
scientifically and ethically appropriate and does not conflict with
constraints or informed consent limitations identified by the
institutions that submitted the dataset to the NIH GWAS data
repository. In the event that requests raise concerns related to
privacy and confidentiality, risks to populations or groups, or other
concerns, the DAC will consult with other experts as appropriate.
IV. Publication
The NIH expects that investigators who contribute data to the NIH
GWAS data repository will retain the exclusive right to publish
analyses of the dataset for a defined period of time following the
release of a given genotype-phenotype dataset through the NIH GWAS data
repository (including the pre-computed analyses of the data). During
this period of exclusivity, the NIH will grant access through the DACs
to other investigators, who may analyze the data, but are expected not
to submit their analyses or conclusions for publication during the
exclusivity period. The maximum period of exclusivity is twelve months
from the date that the GWAS dataset is made available for access
through the NIH GWAS data repository, although a shorter period of
exclusivity may be determined by the NIH funding IC. Contributing
investigators are encouraged to shorten the period of publication
exclusivity at their own discretion. Publication exclusivity is
expected to extend to all forms of public disclosure, including meeting
abstracts, oral presentations, and publicly accessible electronic
submissions (e.g., Web sites, web blogs). Following expiration of the
exclusive publication period for a given GWAS dataset, the NIH expects
that all investigators with access to the data may submit publications
or present analyses for any purpose consistent with the practices and
policies of their institutions and the NIH. The NIH also expects all
investigators who access GWAS datasets to acknowledge the Contributing
Investigator(s) who conducted the original study, the funding
organization(s) that supported the work, and the NIH GWAS data
repository in all resulting oral or written presentations, disclosures,
or publications of the analyses.
V. Intellectual Property
It is the hope of the NIH that genotype-phenotype associations
identified through NIH-supported and NIH-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 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 certain
automated calculations (described under the Data Access section) as a
component of the GWAS datasets distributed through the NIH GWAS data
repository.
The NIH expects that NIH-supported genotype-phenotype data made
available through the NIH 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
[[Page 49297]]
drugs, therapeutics, and diagnostics. The intent is to discourage the
use of patents to 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 the NIH's Best Practices
for the Licensing of Genomic Inventions (http://www.ott.nih.gov/policy/genomic_invention.html) and its Research Tools Policy (http://
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 diminish 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 Defined in the Policy for Investigators
The detailed expectations are enumerated in the individual sections
of this policy, and summarized as follows:
Investigators Submitting GWAS Data Are Expected To
Provide descriptive information about their studies;
Submit coded genotypic and phenotypic data to the NIH GWAS
data repository; and
Submit certification by the Institutional Official(s) of
the responsible submitting institution that it has reviewed and
approved submission to the NIH, noting any limitations on data use
based on the relevant informed consents and providing assurance that
all data are submitted to the NIH in accord with applicable laws and
regulations and that the identities of research participants will not
be disclosed to the NIH GWAS data repository.
Investigators Requesting and Receiving GWAS Data Are Expected To
Submit a description of the proposed research project;
Submit a data access request, including a Data Use
Certification co-signed by the designated Institutional Official(s) at
their sponsoring institution;
Protect data confidentiality;
Ensure that data security measures are in place;
Notify the appropriate Data Access Committee of policy
violations; and
Submit annual progress reports detailing significant
research findings.
Inquiries
Specific questions about this Notice should be directed to: Laura
Lyman Rodriguez, PhD, Special Advisor to the Director, National Human
Genome Research Institute, 31 Center Drive, Room 4B09, Bethesda, MD
20892, Phone: 301-496-0844. Sam Shekar, M.D., M.P.H., Assistant Surgeon
General and Director, Office of Extramural Programs, Office of
Extramural Research, 1 Center Drive, Bethesda, MD 20892, Phone: 301-
435-3492.
E-mail inquiries should be directed to GWAS@nih.gov.
Additional information and detailed implementation guidance related
to the NIH GWAS Policy will be provided at http://grants.nih.gov/grants/gwas/index.htm
.
Dated: August 22, 2007.
Elias A. Zerhouni,
Director, National Institutes of Health.
[FR Doc. E7-17030 Filed 8-27-07; 8:45 am]
BILLING CODE 4140-01-P