FOA Title: 
NIH Genomic Data Sharing Policy
Grant Type: 
NOT-OD-14-124
Primary IC: 
NIH
Release Date: 
Aug 27 2014
Expiration Date: 
N/A
AC Source: 
N/A
Purpose: 
NIH Genomic Data Sharing Policy Notice Number: NOT-OD-14-124 Key Dates Release Date:   August 27, 2014 Related Announcements NOT-OD-17-110 NOT-HG-15-038 NOT-OD-15-086 NOT-OD-15-083 NOT-OD-15-027 NOT-OD-14-111 NOT-OD-13-119 NOT-OD-12-136 NOT-HG-10-006 NOT-OD-08-013 NOT-OD-07-088 NOT-OD-07-088 NOT-MH-19-033 NOT-OD-19-023 --> Issued National Institutes Health NIH) Purpose Summary National Institutes Health NIH) announces final Genomic Data Sharing GDS) Policy promotes sharing, research purposes, large-scale human non-human genomic1 data generated NIH-funded research.  summary public comments the draft GDS Policy NIH’s responses also provided. Introduction NIH announces final Genomic Data Sharing GDS) Policy, sets forth expectations ensure broad responsible sharing genomic research data.  Sharing research data supports NIH mission is essential facilitate translation research results knowledge, products, procedures improve human health.  NIH longstanding policies make broad range research data, addition genomic data, publicly available a timely manner the research activities it funds.2,3,4,5,6   NIH published Draft NIH Genomic Data Sharing Policy Request Public Comments the Federal Register September 20, 2013,7 the NIH Guide Grants Contracts September 27, 2013,8 a 60-day public comment period ended November 20, 2013.  NIH also used websites, listservs, social media disseminate request comments.  November 6, 2013, during comment period, NIH held public webinar the draft GDS Policy was attended nearly 200 people included question answer session.9  NIH received total 107 public comments the draft GDS Policy.  Comments submitted individuals, organizations, entities affiliated academic institutions, professional scientific societies, disease patient advocacy groups, research organizations, industry commercial organizations, tribal organizations, state public health agencies, private clinical practices.  public comments been posted the NIH GDS website.10  Comments supportive the principles sharing data advance research.  However, were number questions concerns, calls clarification specific aspects the draft Policy.  summary comments, organized corresponding sections the GDS Policy, provided below. Scope Applicability Several commenters stated the draft Policy unclear regard the types research which Policy apply.  commenters suggested the technology used a research study i.e., array-based high-throughput genomic technologies) should be focus determining applicability the Policy.  suggested instead the information gained the research should determine applicability the Policy.  other commenters expressed concern the Policy overly broad would lead the submission large quantities data low utility other investigators.  Several commenters suggested the scope the Policy not broad enough.  Additionally, commenters uncertain whether Policy apply research funded multiple sources. NIH revised Scope Applicability section help clarify types research which Policy intended apply, the reference specific technologies been dropped.  list examples the types research projects are within Policy’s scope, appeared Appendix of draft GDS Policy referred as Supplemental Information the NIH Genomic Data Sharing Policy”11), been revised expanded, examples research are within scope been added well.  Also, final GDS Policy explicitly states smaller studies e.g., sequencing genomes fewer 100 human research participants) generally subject this Policy.  Smaller studies, however, be subject other NIH data sharing policies e.g., National Institute Allergy Infectious Diseases Data Sharing Release Guidelines12) program requirements.  addition, definitions key terms used the Policy e.g., aggregate data) been included other terms been clarified.  statement scope remains intentionally general enough accommodate evolving nature genomic technologies the broad range research generates genomic data.  also allows the possibility individual NIH Institutes Centers IC) choose a case-by-case basis apply Policy projects generating data a smaller scale depending the state the science, needs the research community, the programmatic priorities the IC.  Policy applies research funded part in total NIH NIH funding supports generation the genomic data.  Investigators questions whether Policy applies their current proposed research should consult relevant Program Official Program Officer the IC’s Genomic Program Administrator GPA).  Names contact information GPAs available through NIH GDS website.13 commenters expressed concern the financial burden investigators institutions validating sharing large volumes genomic data the possibility resources spent support data sharing redirect funds away research.  While resources needed support data sharing not trivial, NIH maintains the investments warranted the significant discoveries possible through secondary of data.  addition, NIH taking steps evaluate monitor impact data sharing costs the conduct research, both programmatically through Big Data Knowledge Initiative14 organizationally through creation the Scientific Data Council, will advise agency issues related data science.15 Data Sharing Plans commenters pointed that Policy not clear enough the conditions under NIH grant exception the submission genomic data NIH.  also suggested NIH should allow limited sharing human genomic data the original consent national, tribal, state laws not permit broad sharing.  While NIH encourages investigators seek consent broad sharing, some ICs establish program priorities expect studies proposed funding include consent broad sharing, exceptions be made.  final Policy clarifies exceptions be requested cases where submission genomic data not meet criteria the Institutional Certification.  commenters expressed concern it be difficult estimate resources required support data sharing plans before study completed.  Others asked additional guidance resources should requested support data sharing plan.  Several commenters suggested NIH should allow certain elements the data sharing plan, such the Institutional Certification associated documentation, be submitted along other Just-in-Time” information.  multi-year awards, commenter suggested the data sharing plans should periodically reviewed consistency contemporary ethical standards.  Another suggested data sharing plans should made public.  Under GDS Policy, investigators expected outline the budget section their funding application resources will need prepare data submission appropriate repositories.  NIH provide additional guidance these resources, necessary.  final Policy clarifies only basic genomic data sharing plan, the Resource Sharing Plan section grant applications, needs be submitted the funding application that more detailed plan should provided prior award.  Institutional Certification also should provided prior award, along any Just-in-Time information.  Guidance genomic data sharing plans available the NIH GDS website.16  Data sharing plans undergo periodic review through annual progress reports other appropriate scientific project reviews.  Further consideration be given the suggestion data sharing plans should made public.  Non-human Model Organism Genomic Data draft GDS Policy proposed timelines data submission data release i.e., data should made available sharing other investigators).  non-human data, draft Policy proposed data should submitted made available sharing later the date initial publication, the acknowledgement the submission release data certain projects be expected earlier, mirroring data sharing expectations have in place under policies.4  commenters suggested the data submission expectations non-human data unclear.  commenter suggested NIH should consider more rapid timeline the date first publication releasing model organism data, while comments supported specified data release timeline.  commenters concerned the specified timeline too short. final GDS Policy does change timeline the submission release non-human model organism data.  timeline based the need promote broad data sharing while also accommodating investigators generating data, often must a significant effort prepare data sharing.  Policy points that NIH IC choose shorten timeline data submission release certain projects expects investigators work NIH Program Project Officials specific guidance the timelines milestones their projects. was broad support the Policy’s flexibility allowing non-human model organism data be deposited any widely used data repository.  commenter requested a link reference non-NIH-designated repositories included the Policy.  Further information NIH-designated repositories, including examples such repositories, available the GDS website,17 additional information non-NIH-designated data repositories be incorporated outreach training materials NIH staff investigators made available the GDS website.  NIH clarified final Policy state data types were previously submitted widely used repositories e.g., gene expression data the Gene Expression Omnibus Array Express) should continue before, while data types previously submitted go these other widely used repositories agreed by funding IC. Human Genomic Data Supplemental Information the NIH GDS Policy10 establishes timelines the submission subsequent release data access secondary investigators based the level processing the data undergone.  number commenters expressed concern these timelines, suggesting they too short could limit investigator’s ability perform adequate quality control publish results within provided timeline.  commenters proposed the timeline data release extended 12 18 months be date publication, whichever comes first.  Others concerned the timelines too long that should reflect longstanding principle rapid data release articulated the Bermuda Ft. Lauderdale agreements.5  commenters concerned the elimination the embargo period, i.e., period between a study released secondary research when submitting investigator first publishes the findings the study) adversely affect goal rapid data release.  commenter concerned data be released before investigators discuss consequential findings participants. NIH modified Supplemental Information clarify the 6-month deferral the release Level 2 Level 3 human genomic data does start until data been cleaned submission NIH been initiated, is typically three months after data been generated.  Because will significant variation research projects generating Level 2 Level 3 human genomic data, timeline submission project-specific will determined each case the funding NIH IC through consultation the investigator, the Supplemental Information been clarified accordingly.  Under GWAS Policy,6 publication embargo period used a of making data rapidly available.  exchange immediate data access, secondary users not permitted publish present research findings until 12 months after data released.  NIH not adopt approach the GDS Policy because practice, publication embargo dates difficult secondary users track, especially datasets had multiple embargo periods certain types data, raising risk unintentional embargo violations.  Regarding concern human genomic data be available before investigators notify participants consequential findings, such data be considered Level 4 data would be expected be released before publication, NIH believes provide sufficient time discuss consequential findings participants. commenters called the Policy include technical data standards the submission human genomic data, such platform information, controlled vocabulary, normalization algorithms, data quality standards, metadata standards.  NIH agrees the importance developing using standards genomic data is aware there numerous initiatives underway develop promote such standards.18  NIH revised Supplemental Information adding section resources data standards.  provides references instructions data submission specific NIH-designated data repositories, include data standards.  Additional resources data standards be incorporated the Supplemental Information they developed become appropriate broad use.  Several commenters asked a definition an NIH-designated data repository for guidance determining non-NIH repositories acceptable well examples such repositories.  Commenters also expressed interest additional details regarding use Trusted Partners, are third-party partnerships established through contract mechanism, provide infrastructure needs data storage and/or tools are useful genomic data analyses.  definition an NIH-designated repository now included the final Policy.  Additionally, further information non-NIH-designated repositories accept human genomic data be available the GDS website incorporated outreach training materials NIH staff NIH-funded investigators.  Additional information Trusted Partners, including standards required trusted partnerships, also available the NIH GDS website.16  Regarding informed consent, GDS Policy expects investigators generating genomic data seek consent participants future research uses the broadest possible sharing.  number commenters concerned participants not agree consent broad sharing that enrollment research studies decline, potentially biasing studies certain populations less likely consent broad of data.  commenters also raised concern the competitiveness an application proposed obtain consent more limited sharing data.  Several commenters suggested NIH permit alternative forms informed consent than broad consent, such dynamic consent tiered consent. NIH recognizes consent future research uses broad sharing not appropriate obtainable all circumstances.  ICs continue accept data studies consents stipulate limitations future uses sharing, NIH maintain data access system enables limited sharing secondary use.  regard the competitiveness grant applications do propose utilize consent broad sharing, Policy does propose applications assessed this point during merit review, investigators nonetheless expected seek consent broad sharing the greatest extent possible.  breadth the sharing permitted the consent be taken consideration during program priority review the ICs.  Regarding alternative forms consent, Policy does prohibit use dynamic tiered consents.  promotes use consent broad sharing enable greatest potential public benefit.  However, NIH recognizes changing technology enable dynamic consent processes improve tracking oversight more closely reflect participant preferences.  NIH continue monitor developments this area. Several commenters unsure whether GDS Policy apply research clinical settings research involving data deceased individuals.  Research falls within scope the GDS Policy be subject the Policy, regardless whether occurs a clinical setting involves data generated deceased individuals. Several commenters also expressed concern the Policy unclear the ability groups, addition participants, opt-out withdraw informed consent research whether ability withdraw be transferred inherited.  Policy states investigators institutions request NIH withdraw data the event individual participants groups withdraw consent secondary research, although data have distributed research cannot retrieved.  Institutions submitting data should determine whether data should withdrawn NIH repositories notify NIH accordingly.  commenters urged NIH develop standard text templates informed consent documents that investigators be assured their consent material be consistent the Policy’s expectations informed consent data sharing.  of commenters noted challenge conveying necessary information e.g., broad future research uses) without adding the complexity consent forms.  Developing educational materials tools guide process obtaining informed consent also suggested.  commenters expressed concern the burden rewriting harmonizing existing informed consent documents.  NIH appreciates suggestion develop template consent documents plans provide guidance assist investigators institutions developing informed consent documents.  comments questioned proposal require explicit consent research is considered humans subjects research under 45 CFR Part 46 e.g., research involves de-identified specimens cell lines).  were also several comments the draft GDS Policy proposal grandfather data de-identified clinical specimens cell lines collected generated before effective date the GDS Policy.  reason Policy expects consent research the of data generated de-identified clinical specimens cell lines created after effective date the Policy because evolution genomic technology analytical methods raises risk re-identification.19  Moreover, requiring consent obtained respectful research participants, it increasingly clear participants expect be asked their permission use share de-identified specimens research.20,21,22  Policy does require consent be obtained research data generated de-identified clinical specimens cell lines were created collected before effective date the Policy because the practical ethical limitations recontacting participants obtain new consent existing collections the fact such data have already widely used research. draft GDS Policy included exception compelling scientific reasons” allow research of data de-identified, clinical specimens cell lines collected created after effective date the Policy for research consent not obtained.  Commenters not object the need such exception, they asked clarification what constitutes compelling scientific reason,” the process through investigators’ justifications be determined be appropriate.  funding IC determine whether investigators’ justifications the of clinical specimens cell lines which consent research obtained acceptable, provided their funding application Institutional Certification.  Further guidance what constitutes compelling scientific reasons be available the GDS website will likely evolve over time NIH ICs, NIH GDS governance system, program project staff acquire greater experience requests research such specimens.  clinical specimens cell lines lacking consent research collected before effective date the Policy, several commenters concerned the Policy unclear whether data such specimens be deposited NIH repositories.  provision the Policy intended allow research of genomic data derived de-identified clinical specimens cell lines collected created after Policy’s effective date exceptional situations where proposed research the potential advance scientific medical knowledge significantly could be conducted consented specimens cell lines.  draft GDS Policy stated NIH accept data clinical specimens cell lines lacking consent research that collected before effective date the Policy, this remains unchanged the final Policy. concern shared several commenters that risks posed the privacy individuals rare diseases, populations higher risk re-identification the broad sharing data, populations risk greater potential harm re-identification not adequately addressed.  Several commenters particularly concerned no additional protections specified these populations, a subset suggested research subject the GDS Policy involves populations should entirely exempt the Policy’s expectations data sharing. Currently, NIH requests Institutional Review Boards IRBs) consider ethical concerns related groups populations determining whether study’s consent documents consistent NIH policy.23  addition, NIH clarified the final GDS Policy exceptions be requested the submission subsequent sharing data the criteria the Institutional Certification cannot met e.g., IRB equivalent body cannot assure submission data subsequent sharing research purposes consistent the informed consent study participants).  a submitting institution determines the criteria be met has additional concerns related the sharing the data, institution indicate additional stipulations the of data through data limitations submitted the study. Several commenters suggested return medically actionable incidental findings should included the consent that re-identification participants should allowed order return such incidental results.  NIH recognizes that, in any research study, harms result individual research findings have been clinically validated returned subjects are used prematurely clinical decision-making.  return individual findings studies using data obtained NIH-designated repositories expected be rare, because investigators not able return individual research results directly a participant neither nor repository have access the identities participants.  Submitting institutions their IRBs wish establish policies determining it appropriate return individual findings research studies.  Further guidance the return results available the Presidential Commission the Study Bioethical Issues’ report, Anticipate Communicate: Ethical Management Incidental Secondary Findings the Clinical, Research, Direct-to-Consumer Contexts.”24 Several commenters concerned the draft GDS Policy unclear which standard should used ensure de-identification data.  Another issue raised a number comments related identifiability genomic data.  Several commenters concerned de-identified genotype data be re-identified, even these data de-identified according Health Insurance Portability Accountability Act HIPAA) the Common Rule.  Others asserted genomic data not fully de-identified.  number commenters suggested the GDS Policy should explicitly state risks exist participant privacy despite de-identification genomic data should require informed consent documents include such statement.  Others suggested the Policy should state genomic information cannot de-identified.  Commenters suggested the risks re-identification not adequately addressed the draft Policy.  final GDS Policy been clarified state for purpose the Policy, data should de-identified meet definition de-identified data the HHS Regulations Protection Human Subjects25 be stripped the 18 identifiers listed the HIPAA Privacy Rule.26  NIH agrees the risks re-identification should conveyed prospective subjects the consent process.  is of reasons why NIH expects explicit consent after effective date the Policy broad sharing for data will submitted unrestricted-access data repositories i.e., openly accessible data repositories, previously referred as open access”).  NIH provide further guidance informing participants the risks re-identification through revisions guidance documents such the NIH Points Consider IRBs Institutions their Review Data Submission Plans Institutional Certifications Under NIH’s Policy Sharing Data Obtained NIH Supported Conducted Genome-Wide Association Studies.24  Several commenters particularly concerned the cost burden obtaining informed consent the research of data generated clinical specimens cell lines collected created after effective date the GDS Policy.  NIH recognizes these consent expectations data de-identified clinical specimens collected after effective date require additional resources.  Given growing concerns re-identification, is longer ethically tenable simply de-identify clinical specimens derived cell lines generate data research without individual’s consent.  addition, NIH anticipates obtaining consent broad future research uses facilitate access greater volumes data ultimately reduce costs burdens associated sharing research data.  commenters expressed concern the draft Policy’s standards consent more restrictive other rules governing human subjects protections including Common Rule27 revisions proposed the Common Rule a 2011 Advance Notice Proposed Rule Making ANPRM).28  commenters sought greater clarification regarding regulatory differences the regulatory basis the draft Policy’s protections.  NIH the authority establish additional policies expectations are required laws regulations advance agency’s mission enhance health, lengthen life, reduce illness disability.  GDS Policy builds the GWAS Policy, established additional expectations were required the Common Rule obtaining consent for, handling, sharing, using human genotype phenotype data NIH-funded research.  NIH expects in addition adhering the GDS Policy, investigators institutions also comply the Common Rule any applicable federal regulations laws.  response the concern the draft Policy inconsistent the ANPRM revisions the Common Rule, NIH evaluate any inconsistencies between GDS Policy the Common Rule the Common Rule revisions final.  Responsibilities Investigators Accessing Using Genomic Data Commenters asserted the draft GDS Policy not enough protect against misuse the data investigators accessing data.  suggested the Policy state responsibilities outlined the Policy data users should required” rather expected” should state there be penalties noncompliance the Policy rigorous sanctions the intentional misuse data.  was also comment proposing a submitting institution should able review comment all data access requests DARs) NIH before NIH completes internal review process proposed NIH notify submitting institutions research participants any policy violations reported users genomic data. NIH Data Access Committees DACs) review DARs behalf submitting institutions using data limitations provided the institutions determine whether DAR consistent the limitations ensure participants’ wishes respected.  part its ongoing oversight process, NIH reviews notifications data mismanagement misuse, such errors the assignment data limitations during data submission, investigators sharing controlled-access data unapproved investigators, investigators using data research was described their research statement.  date, violations been discovered before completion the research, no participants been harmed.  NIH becomes aware any problems, relevant institution investigators notified, NIH takes appropriate steps address violation prevent from recurring.  ensure the penalties the misuse data clear all data submitters, users, research participants, GDS Policy been revised clarify secondary users violation the Policy the Data Certification face enforcement actions.  addition, measure protect confidentiality de-identified data obtained through controlled access been added encouraging approved users consider requesting Certificate Confidentiality. Several comments submitted representatives members tribal organizations data access.  Tribal groups expressed concerns the ability DACs represent tribal preferences the review requests tribal data.  also proposed new provisions the protection participant data, example, including de-identification tribal membership participant de-identification revision the Genomic Data User Code Conduct reference protocols accessing, sharing, using tribal data, such de-identification participants’ tribal affiliation. final Policy been modified reference explicitly tribal law, addition other factors such limitations the original informed consents concerns harms individuals groups, should considered assessing secondary of genomic data.  commenters proposed changes controlled access human genomic data.  commenters thought controlled access unnecessarily limited research, many provided range suggestions how improve process accessing data, such as: allowing unrestricted access de-identified data; developing standard data limitations controlled-access data; streamlining increasing transparency data access procedures processing time; modifying database genotypes phenotypes dbGaP) facilitate peer-review collaboration. final GDS Policy permits unrestricted access de-identified data, only participants explicitly consented sharing data through unrestricted-access mechanisms.  Standard data limitations been developed NIH are available through GDS website.29  regard improving transparency data access procedures, NIH plans make statistics access publicly available the GDS website,30 including average processing time NIH review data access requests.  its inception, dbGaP solicited feedback users worked improve data submission access procedures, example, creation a study compilation allows investigators submit single request access all controlled-access aggregate individual-level genomic data available general research use.31,32  NIH continue seek user feedback track performance the dbGaP system. Several comments expressed concern the GDS Policy increase administrative burden NIH DACs, potentially resulting longer timeframes obtain data maintained under controlled access.  NIH aware the burden may imposed DACs additional data access requests will continue monitor possibility and, needed, develop methods decrease DAC burden improve performance investigators, institutions, NIH ICs. Intellectual Property GDS Policy expects basic sequence certain related data available through NIH-designated data repositories all conclusions derived them be freely available.  discourages patenting upstream” discoveries, are considered pre-competitive, while encourages patenting downstream” applications appropriate intellectual property.  the several comments received intellectual property, supported draft Policy’s provisions.  However, few commenters opposed patenting general, one suggested the Policy should explicitly prohibit rather discourage use patents inventions result research undertaken data NIH-designated repositories.  noted above, NIH encourages appropriate patenting downstream” applications.  NIH continue encourage broadest possible of products, technologies, information resulting NIH funding developed using data obtained NIH data repositories the extent permitted applicable NIH policies, federal regulations laws, while encouraging patenting technology suitable private investment addresses public needs.  is well known, Supreme Court decision Association Molecular Pathology et al. v. Myriad Genetics, Inc. et al. prohibits patenting naturally occurring DNA sequences.33  Consistent this decision, NIH expects patents directed naturally occurring sequences not filed. Conclusion NIH appreciates time effort taken commenters respond the Request Comments.  responses helpful revising draft GDS Policy enhanced understanding additional guidance materials may necessary. Final NIH Genomic Data Sharing Policy I. Purpose National Institutes Health NIH) Genomic Data Sharing GDS) Policy sets forth expectations ensure broad responsible sharing genomic research data.  Sharing research data supports NIH mission  is essential facilitate translation research results knowledge, products, procedures improve human health.  NIH longstanding policies make data publicly available a timely manner the research activities it funds.2,3,4,5,6 II. Scope Applicability GDS Policy applies all NIH-funded research generates large-scale human non-human genomic data well the of data subsequent research.  Large-scale data include genome-wide association studies GWAS),34 single nucleotide polymorphisms SNP) arrays, genome sequence1, transcriptomic, metagenomic, epigenomic, gene expression data, irrespective funding level funding mechanism e.g., grant, contract, cooperative agreement, intramural support).  Supplemental Information the NIH Genomic Data Sharing Policy Supplemental Information)10 provides examples research projects involving large-scale genomic data are subject the Policy.  NIH Institute Centers IC) expect submission data smaller scale research projects based the state the science, programmatic priorities the IC funding research, the utility the data the research community.  appropriate intervals, NIH review types research which Policy be applicable, any changes examples research are within Policy’s scope be provided the Supplemental Information.  NIH notify investigators institutions any changes through standard NIH communication channels e.g., NIH Guide Grants Contracts). NIH expects funded investigators adhere the GDS Policy, compliance this Policy become special term condition the Notice Award the Contract Award.  Failure comply the terms conditions the funding agreement lead enforcement actions, including withholding funding, consistent 45 CFR 74.6235 and/or authorities, appropriate. III. Effective Date Policy applies to: Competing grant applications36 are submitted NIH the January 25, 2015, due date subsequent due dates; Proposals contracts are submitted NIH or after January 25, 2015; NIH intramural research projects generating genomic data or after January 25, 2015. IV. Responsibilities Investigators Submitting Genomic Data A. Genomic Data Sharing Plans Investigators seeking NIH funding should contact appropriate IC Program Official Project Officer37 early possible discuss data sharing expectations timelines would apply their proposed studies.  NIH expects investigators their institutions provide basic plans following Policy the Genomic Data Sharing Plan” located the Resource Sharing Plan section funding applications proposals.  Any resources may needed support proposed genomic data sharing plan e.g., preparation data submission) should included the project's budget.  more detailed genomic data sharing plan should provided the funding IC prior award.  Institutional Certification sharing human data), should also provided the funding IC prior award, along any Just-in-Time information.  NIH expects intramural investigators address compliance genomic data sharing plans their IC scientific leadership prior initiating applicable research are encouraged contact IC leadership the Office Intramural Research guidance.  funding NIH IC typically review compliance genomic data sharing plans the time annual progress reports other appropriate scientific project reviews, at times, depending the reporting requirements specified the IC specific programs projects. B. Non-human Genomic Data Sharing Plans 1. Data Submission Expectations Timeline Large-scale non-human genomic data, including data microbes, microbiomes, model organisms, well relevant associated data e.g., phenotype exposure data), to shared a timely manner.  Genomic data undergo different levels data processing, provides basis NIH’s expectations data submission.  expectations provided the Supplemental Information.  general, investigators should non-human genomic data publicly available later the date initial publication.  However, earlier availability i.e., before publication) be expected certain data IC-funded projects e.g., data projects broad utility a resource the scientific community such microbial population-based genomic studies). 2. Data Repositories Non-human data be available through any widely used data repository, whether NIH-funded not, such the Gene Expression Omnibus GEO),38 Sequence Read Archive SRA),39 Trace Archive,40 Array Express,41 Mouse Genome Informatics MGI),42 WormBase,43 Zebrafish Model Organism Database ZFIN),44 GenBank,45 European Nucleotide Archive ENA),46 DNA Data Bank Japan DDBJ).47  NIH expects investigators continue submitting data types the same repositories they submitted data before effective date the GDS Policy e.g., DNA sequence data GenBank/ENA/DDBJ, expression data GEO Array Express).  Data types previously submitted any repositories be submitted these other widely used repositories agreed by funding IC. C. Human Genomic Data Sharing Plans 1. Data Submission Expectations Timeline Investigators should submit large-scale human genomic data well relevant associated data e.g., phenotype exposure data) an NIH-designated data repository48 a timely manner.  Investigators should also submit any information necessary interpret submitted genomic data, such study protocols, data instruments, survey tools.   Genomic data undergo different levels data processing, provides basis NIH’s expectations data submission timelines the release the data access investigators.  expectations timelines provided the Supplemental Information.  general, NIH release data submitted NIH-designated data repositories later six months after initial data submission begins, at time acceptance the first publication, whichever occurs first, without restrictions publication other dissemination.49 Investigators should de-identify50 human genomic data they submit NIH-designated data repositories according the standards set forth the HHS Regulations the Protection Human Subjects26 ensure the identities research subjects cannot readily ascertained the data.  Investigators should also strip data identifiers according the Health Insurance Portability Accountability Act HIPAA) Privacy Rule.27  de-identified data should assigned random, unique codes the investigator, the key other study identifiers held the submitting institution. Although data the NIH database Genotypes Phenotypes dbGaP) de-identified both HHS Regulations Protection Human Subjects HIPAA Privacy Rule standards, NIH obtained Certificate Confidentiality dbGaP an additional precaution because genomic data be re-identified.51  NIH encourages investigators institutions submitting large-scale human genomic datasets NIH-designated data repositories seek Certificate Confidentiality an additional safeguard prevent compelled disclosure any personally identifiable information may hold.52 2. Data Repositories Investigators should register studies human genomic data fall within scope the GDS Policy dbGaP53 the time data cleaning quality control measures begin, regardless which NIH-designated data repository receive data.  After registration dbGaP, investigators should submit data the relevant NIH-designated data repository e.g., dbGaP, GEO, SRA, Cancer Genomics Hub54).  NIH-designated data repositories need be exclusive source facilitating sharing genomic data, is, investigators also elect submit data a non-NIH-designated data repository addition an NIH-designated data repository.  However, investigators should ensure appropriate data security measures in place,55 that confidentiality, privacy, data measures consistent the GDS Policy. 3. Tiered System the Distribution Human Data Respect for, protection the interests of, research participants fundamental NIH’s stewardship human genomic data.  informed consent under the data samples collected the basis the submitting institution determine appropriateness data submission NIH-designated data repositories whether data should available through unrestricted controlled access.  Controlled-access data NIH-designated data repositories made available secondary research only after investigators obtained approval NIH use requested data a particular project.  Data unrestricted-access repositories publicly available anyone e.g., 1000 Genomes Project56). 4. Informed Consent research falls within scope the GDS Policy, submitting institutions, through Institutional Review Boards26 IRBs), privacy boards,57 equivalent bodies,58 to review informed consent materials determine whether is appropriate data be shared secondary research use.  Specific considerations vary the type study whether data obtained through prospective retrospective data collections.  NIH provides additional information issues related the respect research participant interests its Points Consider IRBs Institutions their Review Data Submission Plans Institutional Certifications.24 studies initiated after effective date the GDS Policy, NIH expects investigators obtain participants’ consent their genomic phenotypic data be used future research purposes to shared broadly.  consent should include explanation whether participants’ individual-level data be shared through unrestricted- controlled-access repositories.  studies proposing use genomic data cell lines clinical specimens59 were created collected after effective date the Policy, NIH expects informed consent future research and broad data sharing have obtained even the cell lines clinical specimens de-identified.  there compelling scientific reasons necessitate use genomic data cell lines clinical specimens were created collected after effective date this Policy that lack consent research and data sharing, investigators should provide justification the funding request their use.  funding IC review justification decide whether make exception the consent expectation. studies using data specimens collected before effective date the GDS Policy, may considerable variation the extent which future genomic research broad sharing addressed the informed consent materials the primary research.  these cases, assessment an IRB, privacy board, equivalent body needed ensure data submission not inconsistent the informed consent provided the research participant.  NIH accept data derived de-identified cell lines clinical specimens lacking consent research that created collected before effective date this Policy.    NIH recognizes in circumstances broad sharing not consistent the informed consent the research participants whose data included the dataset.  such circumstances, institutions planning submit aggregate-60 individual-level data NIH controlled access should note any data limitations the data sharing plan submitted part the funding request.  data limitations should specified the Institutional Certification submitted NIH prior award. 5. Institutional Certification responsible Institutional Signing Official61 the submitting institution should provide Institutional Certification the funding IC prior award consistent the genomic data sharing plan submitted the request funding.  Institutional Certification should state whether data be submitted an unrestricted- controlled-access database.  submissions controlled access and, appropriate unrestricted access, Institutional Certification should assure that: data submission consistent, appropriate, applicable national, tribal, state laws regulations well relevant institutional policies;62 Any limitations the research of data, expressed the informed consent documents, delineated;63 identities research participants not disclosed NIH-designated data repositories; An IRB, privacy board, and/or equivalent body, applicable, reviewed investigator’s proposal data submission assures that: protocol the collection genomic phenotypic data consistent 45 CFR Part 46;28 Data submission subsequent data sharing research purposes consistent the informed consent study participants whom data obtained;64 Consideration given risks individual participants their families associated data submitted NIH-designated data repositories subsequent sharing; the extent relevant possible, consideration given risks groups populations associated submitting data NIH-designated data repositories subsequent sharing; The investigator’s plan de-identifying datasets consistent the standards outlined this Policy section IV.C.1.). 6. Exceptions Data Submission Expectations cases where data submission an NIH-designated data repository not appropriate, is, Institutional Certification criteria cannot met, investigators should provide justification any data submission exceptions requested the funding application proposal.  funding IC grant exception submitting relevant data NIH, the investigator be expected develop alternate plan share data through mechanisms.  transparency purposes, exceptions granted, studies still registered dbGaP, reason the exception be included the registration record, a reference be provided an alternative data-sharing plan resource, available.  information requesting exceptions available the GDS website.15 7. Data Withdrawal Submitting investigators their institutions request removal data individual participants NIH-designated data repositories, the event a research participant withdraws changes or consent.  However, data have distributed approved research cannot retrieved. V. Responsibilities Investigators Accessing Using Genomic Data A. Requests Controlled-Access Data Access human data through tiered model involving unrestricted- controlled-data access mechanisms.  Requests controlled-access data65 reviewed NIH Data Access Committees DACs).66  DAC decisions based primarily upon conformance the proposed research described the access request the data limitations established the submitting institution through Institutional Certification.  NIH DACs accept requests proposed research uses beginning month prior the anticipated data release date.  access period all controlled-access data one year; the end each approved period, data users request additional year access close the project.  Although data de-identified, approved users controlled-access data encouraged consider whether Certificate Confidentiality serve an additional safeguard prevent compelled disclosure any genomic data may hold.55 B. Terms Conditions Research of Controlled-Access Data Investigators approved download controlled-access data NIH-designated data repositories their institutions expected abide the NIH Genomic Data User Code Conduct67 through agreement the Data Certification.68  Data Certification, co-signed the investigators requesting data their Institutional Signing Official, specifies conditions the secondary research of controlled-access data, including: Using data only the approved research; Protecting data confidentiality; Following, appropriate, applicable national, tribal, state laws regulations, well relevant institutional policies procedures handling genomic data; attempting identify individual participants whom data obtained; selling any the data obtained NIH-designated data repositories; sharing any the data obtained controlled-access NIH-designated data repositories individuals than those listed the data access request; Agreeing the listing a summary approved research uses dbGaP along the investigator’s name organizational affiliation; Agreeing report any violation the GDS Policy the appropriate DAC(s) soon it discovered; Reporting research progress using controlled-access datasets through annual access renewal requests project close-out reports; Acknowledging all oral written presentations, disclosures, publications contributing investigator(s) conducted original study, funding organization(s) supported work, specific dataset(s) applicable accession number(s), the NIH-designated data repositories through the investigator accessed any data. NIH expects investigators are approved use controlled-access data follow guidance security best practices58 outlines expected data security protections e.g., physical security measures user training) ensure the data kept secure not released any person permitted access data. investigators violate terms conditions secondary research use, NIH take appropriate action.  Further information available the Data Certification. C. Conditions Use Unrestricted-Access Data Investigators download unrestricted-access data NIH-designated data repositories should: attempt identify individual human research participants whom data obtained;69 Acknowledge all oral written presentations, disclosures, publications specific dataset(s) applicable accession number(s) the NIH-designated data repositories through the investigator accessed any data. VI. Intellectual Property NIH encourages patenting technology suitable subsequent private investment may lead the development products address public needs without impeding research.  However, is important note naturally occurring DNA sequences not patentable the United States.34  Therefore, basic sequence data certain related information e.g., genotypes, haplotypes, p-values, allele frequencies) pre-competitive.  Such data available through NIH-designated data repositories, all conclusions derived directly them, should remain freely available, without any licensing requirements.    NIH encourages broad of NIH-funded genomic data is consistent a responsible approach management intellectual property derived downstream discoveries, outlined the NIH Best Practices the Licensing Genomic Inventions70 Section 8.2.3, Sharing Research Resources, the NIH Grants Policy Statement.71  NIH discourages use patents prevent use or block access genomic genotype-phenotype data developed NIH support. References 1. genome the entire set genetic instructions found a cell.  http://ghr.nlm.nih.gov/glossary=genome. 2. Final NIH Statement Sharing Research Data. February 26, 2003.  https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html. 3. NIH Intramural Policy Large Database Sharing. April 5, 2002.  http://sourcebook.od.nih.gov/ethic-conduct/large-db-sharing.htm. 4. NIH Policy Sharing Model Organisms Biomedical Research.  7, 2004.  https://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html. 5. Reaffirmation Extension NHGRI Rapid Data Release Policies: Large-scale Sequencing Other Community Resource Projects.  February 2003.  https://www.genome.gov/10506537. 6. NIH Policy Sharing Data Obtained NIH Supported Conducted Genome-Wide Association Studies GWAS).  https://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html. 7. Federal Register Notice.  Draft NIH Genomic Data Sharing Policy Request Public Comments.  http://www.federalregister.gov/a/2013-22941. 8. NIH Guide Grants Contracts.  Request Information: Input the Draft NIH Genomic Data Sharing Policy.  September 27, 2013.  https://grants.nih.gov/grants/guide/notice-files/NOT-OD-13-119.html. 9. Public Consultation Webinar.  Draft NIH Genomic Data Sharing Policy.  November 6, 2013.  https://webmeeting.nih.gov/p7sqo6avp6j/. 10. Compiled Public Comments the Draft Genomic Data Sharing Policy.  http://gds.nih.gov/pdf/GDS_Policy_Public_Comments.PDF. 11. Supplemental Information the NIH Genomic Data Sharing Policy.  http://gds.nih.gov/pdf/supplemental_info_GDS_Policy.pdf. 12. National Institute Allergy Infectious Diseases.  Data Sharing Release Plans.  http://www.niaid.nih.gov/labsandresources/resources/dmid/pages/data.aspx. 13. Roster NIH Genomic Program Administrators.   http://gds.nih.gov/04po2_2GPA.html. 14. NIH Big Data Knowledge.  http://bd2k.nih.gov. 15. NIH Big Data Knowledge.  Scientific Data Council.  http://bd2k.nih.gov/about_bd2k.html#sdcmembership. 16. Genomic Data Sharing Website.  Resources Investigators Submitting Data dbGaP.  http://gds.nih.gov/06researchers1.html. 17. Genomic Data Sharing Website.  Data Repositories.  http://gds.nih.gov/02dr2.html. 18. for example Genomic Standards Consortium, http://gensc.org/; Global Alliance, http://www.broadinstitute.org/news/globalalliance; the NIH Big Data Knowledge focus community-based data metadata standards, http://bd2k.nih.gov/about_bd2k.html#areas. 19. Gymrek et al.  Identifying Personal Genomes Surname Inference.  Science. 339(6117): 321-324.  2013). 20. Kaufman et al.  Public Opinion the Importance Privacy Biobank Research.  American Journal Human Genetics.  85(5): 643-654.  2009). 21. Vermeulen et al.  Trial Consent Procedures Future Research Clinically Derived Biological Samples.  British Journal Cancer.  101(9): 1505-1512.  2009). 22. Trinidad et al.  Research Practice Participant Preferences: Growing Gulf.  Science.  331(6015): 287-288.  2011). 23. NIH Points Consider IRBs Institutions their Review Data Submission Plans Institutional Certifications Under NIH’s Policy Sharing Data Obtained NIH Supported Conducted Genome-Wide Association Studies GWAS).  http://gds.nih.gov/pdf/PTC_for_IRBs_and_Institutions_revised5-31-11.pdf. 24. Presidential Commission the Study Bioethical Issues.  Anticipate Communicate: Ethical Management Incidental Secondary Findings the Clinical, Research, Direct-to-Consumer Contexts.  December 2013.   http://bioethics.gov/node/3183. 25. Code Federal Regulations.  Protection Human Subjects.  Definitions.  45 CFR 46.102(f) http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.102. 26. list HIPAA identifiers must removed available 45 CFR 164.514(b)(2).  See: http://www.gpo.gov/fdsys/pkg/CFR-2002-title45-vol1/pdf/CFR-2002-title45-.... 27. Federal Policy the Protection Human Subjects Common Rule).  45 CFR Part 46.  http://www.hhs.gov/ohrp/humansubjects/commonrule/. 28. ANPRM Revision Common Rule.  http://www.hhs.gov/ohrp/humansubjects/anprm2011page.html. 29. Genomic Data Sharing Website.  Standard Data Limitations.  http://gds.nih.gov/pdf/standard_data_use_limitations.pdf. 30. Genomic Data Sharing Website.  http://gds.nih.gov/. 31. dbGaP Compilation Aggregate Genomic Data General Research Use.  http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs0.... 32. dbGaP Collection: Compilation Individual-Level Genomic Data General Research Use.  http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/collection.cgi?study_id.... 33. Association Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. ___ 2013) slip opinion 12-398).  http://www.supremecourt.gov/opinions/12pdf/12-398_1b7d.pdf. 34. GWAS the same definition this policy in 2007 GWAS Policy: study which density genetic markers the extent linkage disequilibrium should sufficient capture the r2 parameter) large proportion the common variation the genome the population under study, the number samples a case-control trio design) should provide sufficient power detect variants modest effect. 35. 45 CFR 74.62.  Uniform Administrative Requirements Awards Subawards Institutions Higher Education, Hospitals, Nonprofit Organizations, Commercial Organizations; Enforcement.  http://www.gpo.gov/fdsys/pkg/CFR-2011-title45-vol1/xml/CFR-2011-title45-.... 36. Competing grant applications encompass activities a research component, including not limited the following: Research Grants Rs), Program Projects Ps), Cooperative Research Mechanisms Us), Career Development Awards Ks), SCORs other S grants a research component. 37. Investigators should refer funding announcements IC websites contact information. 38. Gene Expression Omnibus http://www.ncbi.nlm.nih.gov/geo/. 39. Sequence Read Archive http://www.ncbi.nlm.nih.gov/Traces/sra/sra.cgi. 40. Trace Archive http://www.ncbi.nlm.nih.gov/Traces/trace.cgi. 41. Array Express http://www.ebi.ac.uk/arrayexpress/. 42. Mouse Genome Informatics http://www.informatics.jax.org/. 43. WormBase http://www.wormbase.org. 44. Zebrafish Model Organism Database http://zfin.org/. 45. GenBank http://www.ncbi.nlm.nih.gov/genbank/. 46. European Nucleotide Archive http://www.ebi.ac.uk/ena/. 47. DNA Data Bank Japan http://www.ddbj.nig.ac.jp/. 48. NIH-designated data repository any data repository maintained supported NIH either directly through collaboration. 49. period data preparation anticipated prior data submission NIH, the appropriate time intervals that data preparation data cleaning) be subject the particular data type project plans Supplemental Information).  Investigators should work NIH Program Project Officials specific guidance. 50. De-identified refers removing information could used associate dataset record a human individual. 51. Confidentiality Certificate. HG-2009-01.  Issued the National Center Biotechnology Information, National Library Medicine, NIH.  http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/GetPdf.cgi?document_nam.... 52. additional information Certificates Confidentiality, https://grants.nih.gov/grants/policy/coc/. 53. Database Genotypes Phenotypes http://www.ncbi.nlm.nih.gov/gap. 54. Cancer Genomics Hub https://cghub.ucsc.edu/. 55. dbGaP Security Best Practices.  http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/GetPdf.cgi?document_nam.... 56. 1000 Genomes Project http://www.1000genomes.org/. 57. the roles Privacy Boards elaborated 45 CFR 164 http://www.gpo.gov/fdsys/pkg/CFR-2011-title45-vol1/pdf/CFR-2011-title45-....  58. Equivalent body used here acknowledge some primary studies be conducted abroad in such cases expectation that analogous review committee an IRB privacy board e.g., Research Ethics Committees) be asked participate the presubmission review proposed genomic projects. 59. Clinical specimens specimens have obtained through clinical practice. 60. Aggregate data summary statistics compiled multiple sources individual-level data. 61. Institutional Signing Official generally senior official an institution is credentialed through NIH eRA Commons system is authorized enter institution a legally binding contract sign behalf an investigator has submitted data a data access request NIH. 62. the submission data derived cell lines clinical specimens lacking research consent were created collected before effective date this Policy, Institutional Certification needs address only item. 63. guidance clearly communicating inappropriate data uses, NIH Points Consider Drafting Effective Data Limitation Statements, http://gwas.nih.gov/pdf/NIH_PTC_in_Drafting_DUL_Statements.pdf. 64. noted earlier, studies using data specimens collected before effective date this Policy, IRB, privacy board, equivalent body should review informed consent materials ensure data submission not inconsistent the informed consent provided the research participants. 65. dbGaP Authorized Access.  https://dbgap.ncbi.nlm.nih.gov/aa/wga.cgi?page=login. 66. a list NIH Data Access Committees, http://gwas.nih.gov/04po2_1DAC.html. 67. Genomic Data User Code Conduct.  http://gds.nih.gov/pdf/Genomic_Data_User_Code_of_Conduct.pdf. 68. Model Data Certification Agreement.  http://gwas.nih.gov/pdf/Model_DUC_7-26-13.pdf. 69. certain cases, NIH consider approving research intended enhance genomic data privacy protection procedures. 70. NIH Best Practices the Licensing Genomic Inventions.  http://www.ott.nih.gov/sites/default/files/documents/pdfs/70fr18413.pdf. 71. NIH Grants Policy Statement. 8.2.3, Sharing Research Resources.  https://grants.nih.gov/grants/policy/nihgps_2012/nihgps_ch8.htm#_Toc2712.... Inquiries Please direct inquiries to: Genomic Data Sharing Policy Team Office Science Policy Telephone: 301-496-9838 Email: GDS@mail.nih.gov