FOA Title: 
Request for Comments: Proposal to Update Data Management of Genomic Summary Results Under the NIH Genomic Data Sharing Policy
Grant Type: 
Primary IC: 
Release Date: 
Sep 20 2017
Expiration Date: 
AC Source: 
Request Comments: Proposal Update Data Management Genomic Summary Results Under NIH Genomic Data Sharing Policy Notice Number: NOT-OD-17-110 Key Dates Release Date: September 20, 2017 Response Date: October 20, 2017 Related Announcements NOT-OD-18-104 NOT-OD-07-088 NOT-OD-12-136 NOT-OD-14-124 NOT-OD-17-044 NOT-OD-19-023 NOT-OD-19-011--> Issued National Institutes Health NIH) Purpose National Institutes Health NIH) seeking public comments regarding proposed update the access procedures genomic summary results under Genomic Data Sharing GDS) Policy.1 Genomic summary results, also known aggregate genomic data’2 genomic summary statistics’ 3, results primary analyses genomic research convey information relevant understanding genomic associations traits diseases across datasets rather data specific any individual research participant. goal this proposed data management update to provide access genomic summary results through methods proportional the risks benefits posed this type information. Background Overview NIH’s mission to seek fundamental knowledge the nature behavior living systems the application that knowledge enhance health, lengthen life, reduce illness disability.4 Broad responsible sharing genomic summary results generated through analysis NIH-supported research promotes maximum public benefit the federal research investment providing information crucial the interpretation application genomic data research clinical practice. Genomic summary results an analytic output derived a study’s primary genomic data are currently defined the agency include calculated summary statistics, such genotype counts frequencies, allele counts frequencies, effect size estimates standard errors, likelihoods, p-values. Genomic summary results facilitate interpretation genomic variants may may not) contribute a disease disorder interest. Public sharing genomic summary results large-scale genomic research become crucial advancing scientific clinical discovery.5 However, studies available through NIH-designated data repository6, access this information currently only available through controlled access below an explanation controlled access’). Based input the research community over past few years below), NIH proposing allow broader access genomic summary results most studies subject the NIH GDS Policy. Institutions submitting genomic data NIH-designated data repositories be expected notify NIH any studies which are particular sensitivities i.e., studies including potentially stigmatizing traits, with identifiable isolated study populations). Access genomic summary results such datasets remain under controlled access. NIH committed safeguarding interests study participants maintaining public trust biomedical research. Therefore, NIH seeking public feedback this proposed data management update. History Access Genomic Summary Results 2007, NIH issued policy sharing data generated through NIH-supported genome wide association studies GWAS),7 launched Database Genotypes Phenotypes dbGaP).8 2014, GWAS Policy subsumed under NIH GDS Policy, applies all large-scale genomic data generated NIH-funded research. Under both policies, dbGaP other NIH-designated data repositories provided data through two-tiered system: 1) unrestricted access, includes descriptions available data, research protocols instruments used collect it, summary-level information the data; 2) controlled access, provides individual-level genomic phenotypic data appropriate research purposes under terms are consistent the informed consent under those data collected. Under NIH GWAS Policy, genomic summary results originally included among summary-level information available through unrestricted access. However, 2008 paper Homer et al. demonstrated statistical method the potential resolve individual’s inclusion a member a research group e.g., within disease group) using genomic summary results.9 Notably, method, well others have followed using genomic information types,10,11 requires independent access a known individual’s whole genome data order predict statistical matches’ information within genomic summary results. NIH responded this development moving genomic summary results controlled access portions NIH-designated data repositories. agency also stated intent further assess risks benefits associated unrestricted access this type information light the new methodology.12 basis the 2008 data management change that matching a known individual a disease case’) group within research study might reveal unknown health phenotype information obvious the independently acquired whole genome data.13   Although NIH maintains genomic summary results dbGaP under controlled-access model, research community since developed several highly utilized valuable public data resources share genomic summary results.14 addition, type information continues be publicly available an element published studies the scientific literature. Despite broad availability genomic summary results, NIH not aware any reported examples date individuals being matched participation a research study beyond research analyses designed demonstrate hypothetical possibility such unintended use.15    NIH Discussions Related Genomic Summary Results Access 2012, NIH held Workshop entitled Establishing Central Resource Data Genome Sequencing Projects”16 consider wide scope issues related aggregating genomic data. During discussions, workshop participants noted value genomic summary results scientific clinical discovery, recommended they publicly available—when appropriate. Also 2012, enable access genomic summary results General Research Use17 studies through single data access request, compilation genomic summary results appropriate studies made available through dbGaP.18,19 addition more efficient access this type information, creation the compilation study’ also it possible reduce unnecessary access individual-level genomic data since, that time, only to obtain access genomic summary results under GDS Policy in conjunction the full data set. 2016, NHGRI convened Workshop entitled Sharing Aggregate Genomic Data” explicitly re-consider risks benefits associated access and of genomic summary results.20  Workshop participants highlighted minimal risk associated public access genomic summary results supported open access model most studies.21  Participants note alternate access models should considered sensitive studies where may heightened concerns.   solicit broad input the risks benefits different access models genomic summary results, NIH included topic the February 2017 Request Information RFI) Processes dbGaP Data Submission, Access, Management.”22 Public comments received suggest support broader access genomic summary results, especially under scenarios include additional risk mitigation strategies genomic summary results sensitive studies.23 Proposed Update Genomic Summary Results Access maximize public benefit genomic information generated through NIH-supported research a manner consistent current scientific ethical considerations,24,25,26,27 NIH promote broad sharing genomic summary results most research studies data held an NIH-designated data repository through new rapid access” tier. Rapid access enable access appropriate genomic summary results after interested users affirm agreement a statement regarding responsible of information below). proposed update the GDS Policy’s data management practices support NIH’s goals promote scientific advances protect research participants’ privacy interests reducing need users request controlled access individual-level genomic data, unless is necessary address specific research questions. addition, proposed data management change establishes access model genomic summary results is proportional the distinct risks associated access this type information relative the risks associated access individual-level genomic data.28 Genomic summary results be available include those provided a study’s investigator, any, well summary statistics computed the relevant NIH-designated data repository across non-sensitive studies data included that repository below). Genomic summary results provided include systematically computed statistics such as, not limited to:  genotype counts frequencies; allele counts frequencies; effect size estimates standard errors; likelihoods; p-values. values be defined calculated using scientifically relevant subsets research participants included within study populations e.g., disease, trait-based, control populations). Information methods computing any summary statistics provided an NIH-designated data repository be available through repository’s website.      is possible privacy risks related broad access genomic summary results be heightened study populations isolated geographic regions with rare traits. is also possible certain study populations be vulnerable group harm due potential stigma related traits being studied other participant protection concerns. addition, studies include data potentially stigmatizing traits, outcomes any privacy breach conceivably cause greater harm research participants is likely under most circumstances. address types sensitivities, institutions submitting datasets NIH-designated data repositories indicate the data sharing plan the Institutional Certification29 genomic summary results such studies should provided only through controlled access.   the purposes this proposed data management update, examples potentially stigmatizing traits expected include, not limited to: illicit drug substance abuse; HIV/AIDS diagnosis; sexual attitudes, preferences, practices. Increased privacy risk heightened risk group harm anticipated stem study populations draw from, are limited to: rare disease communities; studies small sample sizes; isolated identifiable study populations, such indigenous populations underrepresented ethnic groups. Informational Resources support awareness the ethical responsibilities associated responsible of genomic information including genomic summary results), NIH develop informational resources be publicly available through relevant NIH-designated data repositories. Before genomic summary results made accessible through new rapid access’ tier, users affirm they reviewed informational resources provided below). Affirming Responsible of Genomic Summary Results promote responsible of genomic summary results available through rapid access mechanism, users affirm agreement advance science health through use the information. affirmation be achieved via click-through agreement’ users confirm intent use genomic summary results provided responsibly indicating they: 1. Reviewed informational resources available NIH-designated data repositories describing appropriate uses genomic data, including genomic summary results; 2. not attempt re-identify contact any individual group within study population, generate information could allow participants’ identities be readily ascertained; and, 3. promote scientific research health through any of genomic summary results. Informed Consent Consistent the expectations under NIH GDS Policy, NIH expects consent forms the informed consent process human genomic studies clearly articulate access plans data information generated through study, including genomic summary results. NIH expects consent processes other information available potential research participants be transparent participation an NIH-supported study infers acknowledgement investigators aggregate analyze data generated through study. NIH expects consent processes other information explain such analyses other summaries study information including genomic summary results) be shared the scientific literature through public scientific resources, such data sharing resources provide broad unrestricted access the information. Effective Date NIH expects proposed data management update access genomic summary results be effective upon final publication the update.  Proposed Implementation Plans After effective date this data management update, NIH-funded investigators performing research falls under scope the GDS Policy be expected indicate, their Genomic Data Sharing Plan, a study should designated sensitive the purposes access genomic summary results. determination should confirmed the Institutional Certification provided the NIH. datasets submitted to, for data already accessible through, NIH-designated data repositories prior the effective date this data management update, submitting institutions have six months indicate genomic summary results any study submitted one their investigators should maintained controlled access due concerns sensitivity study information. will possible request additional time complete assessment a particular dataset. such cases, genomic summary results that dataset remain controlled access until final determination received the funding Institute Center. a submitting institution confirms appropriateness broader access genomic summary results a particular study prior the end the six-month period, information be available through rapid access tier immediately Request Comments NIH seeking public feedback regarding proposed data management update accessing genomic summary results NIH-funded studies.  NIH encourages comments all stakeholders, is especially interested hearing members the general public, research participants, and/or broader patient community.  NIH seeking overall, general comments any aspect the proposed access model.  NIH also seeking feedback the following specific issues: 1. Risks benefits providing broad access genomic summary results most studies NIH-designated data repositories utilizing proposed rapid access mechanism associated click-through agreement. Risks benefits relate participant protection issues and/or scientific opportunity. 2. Risks benefits maintaining genomic summary results studies designated the submitting institution include sensitive information controlled access. Risks benefits relate participant protection issues and/or scientific opportunity. 3. Appropriateness the proposal institutions submitting study data under NIH GDS Policy indicate datasets should designated sensitive. 4. General comments any topic relevant unrestricted, rapid, controlled-access genomic summary results NIH-funded studies. NIH intends hold least public webinar the proposed data management update the GDS Policy, may also utilize opportunities answer questions receive feedback stakeholders they identified.  Submitting Response Comments the topic areas interest should submitted electronically the following webpage: mailed to: Office Science Policy OSP), National Institutes Health, 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892, by fax to: 301-496-9839 October 20], 2017. Comments received, including any personal information, be posted without change after close the comment period the NIH GDS website Please not include any proprietary, classified, confidential, sensitive information your response. Please note the United States Government not pay the preparation any information submitted for use that information. NIH looks forward your input hope you share RFI document your colleagues. Updates this document, any, be noted. Government reserves right use any non-proprietary technical information summaries the state the science, any resultant solicitation(s). NIH use information gathered this RFI inform development modification data sharing databases, websites, policies practices, processes procedures, supporting documentation e.g., guidance, FAQs). References NIH Genomic Data Sharing Policy. 2 Aggregate data defined the NIH GDS Policy summary statistics compiled multiple sources individual-level data. 3 Summary statistics been defined calculated summary statistics, including genotype counts, allele frequencies, effect size estimates standard errors, p-values calculated a study sample. 4 NIH Mission Goals. 5 Lek, Monkol, et al. Analysis protein-coding genetic variation 60,706 humans." Nature 536, 285–291 18 August 2016). doi:10.1038/nature19057. 6 NIH-designated data repository any data repository maintained supported NIH either directly through collaboration. 7 Policy Sharing Data Obtained NIH Supported Conducted Genome-Wide Association Studies GWAS). 8 NIH Launches dbGaP, Database Genome Wide Association Studies. 9 Homer N, Szelinger S, Redman M, et al. Resolving Individuals Contributing Trace Amounts DNA Highly Complex Mixtures Using High-Density SNP Genotyping Microarrays. Visscher PM, ed. PLoS Genetics. 2008;4(8):e1000167. doi:10.1371/journal.pgen.1000167. 10 Schadt, Eric E., Sangsoon Woo, Ke Hao. Bayesian method predict individual SNP genotypes gene expression data." Nature genetics 44.5 2012): 603-608. 11 Im, Hae Kyung, et al. sharing quantitative trait GWAS results an era multiple-omics data the limits genomic privacy." The American Journal Human Genetics 90.4 2012): 591-598. 12 13 Zerhouni, E.A. Nabel, E.G. Protecting aggregate genomic data. Science. 2008 October 3; 322(5898): 44. Published online 2008 September 4. doi: 10.1126/science.1165490. 14 Genome Aggregation Database gnomAD); Exome Variant Server; Exome Aggregation Consortium ExAC); Type 2 Diabetes Knowledge Portal T2DKP); Michigan Imputation Server; AmbryShare; ClinVar, BRAVO Browse Variants Online, TOPMed’s WGS variant server). 15 Wendler DS, Rid A. Genetic Research Biospecimens Poses Minimal Risk. Trends genetics?: TIG. 2015;31(1):11-15. doi:10.1016/j.tig.2014.10.003. 16Workshop Establishing Central Resource Data Genome Sequencing Projects. 2012. National Institutes Health. 17NIH describes data available general research GRU) data no limitations restrictions beyond limitations outlined the Data Certification Agreement. See: see:  18 Notice New Process Requesting dbGaP Access Aggregate Genomic Data General Research Purposes. 19 20 NHGRI Workshop Sharing Aggregate Genomic Data.   21 Workshop Report Sharing Aggregate Genomic Data. 22 Request Information Processes dbGaP Data Submission, Access, Management. 23 24Erlich Y, Narayanan A. Routes breaching protecting genetic privacy. Nature reviews Genetics. 2014;15(6):409-421. doi:10.1038/nrg3723. 25Wendler DS, Rid A. Genetic Research Biospecimens Poses Minimal Risk. Trends Genetics?: TIG. 2015;31(1):11-15. doi:10.1016/j.tig.2014.10.003. 26 Sanderson, Saskia C., et al. Public Attitudes toward Consent Data Sharing Biobank Research: Large Multi-site Experimental Survey the US." The American Journal Human Genetics 100.3 2017): 414-427. 27 Gutmann, A. W., et al. Privacy progress whole genome sequencing." Presidential Committee the Study Bioethical 2012 2012). 28 Craig, D. W., Goor, R., Wang, Z., Paschall, J., Ostell, J., Feolo, M., & Manolio, T. A. Privacy Summary Level Data’; Assessing Managing Risk Sharing Aggregate Genetic Variant Data. Nature Reviews Genetics. 2011;12(10):730-736. doi:10.1038/nrg3067. 29 Inquiries Please direct inquiries to: NIH Office Science Policy Telephone: 301-496-9838 Email:  
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