1. NIH Genomic Data Sharing (GDS) Policy Kathleen Calzone, PhD, RN, APNG, FAAN Anjan Purkayastha, PhD February 22, 2016

2. The GDS Policy applies to all NIH-funded research that generates large-scale human or non-human genomic data as well as the use of these data for subsequent research Large-scale data include data from genome-wide association studies (GWAS) and single nucleotide polymorphism (SNP) arrays, as well as genome sequence, transcriptomic, metagenomic, epigenomic, and gene expression data, irrespective of funding level and funding mechanism GDS Scope

3. The GDS Policy takes effect for competing grant applications and contract proposals submitted to NIH on or after January 25, 2015. The first round of grant applications submitted for the January 2015 cycle would likely receive funding in the late Summer or early Fall of 2015. To align with this the intramural programs were directed to comply with GDS on data generated on or after August 31, 2015. Genomic Data Sharing Policy Effective Dates

4. Within CCR, GDS will be implemented in phases. In the first phase all Human studies will implement the GDS policy effective December 1, 2015. For ongoing Human studies Genomic Data Sharing Plans should be submitted by December 31, 2015. Implementation of GDS policy across non-human studies will start in the second phase, date TBD. Genomic Data Sharing Policy Effective Dates

5. Thresholds for Data Sharing Expectations * Includes distinct individuals, species, strains, samples, treatments, time points, tissues, etc. Example: Data from 25 patients at 4 time points after treatment would reach a 100 sample threshold; Data from 50 tumor-normal comparisons would reach a 100 sample threshold.

6. Shareable Data: Additional Criteria Examples of smaller-scale projects that the NCI anticipates data sharing for (regardless of study design) include, but are not limited to: Projects examining rare cancers or rare cancer related outcomes, rare cancer subtypes. Projects focusing on under-studied populations. Based on NIH IC priorities, GDS policy may apply to smaller data-sets: State of science NCI’s programmatic priorities Utility of data to research community Journal(s) may require data sharing before publishing your manuscript

7. Examples of Research Outside the Scope of the GDS Policy Examples of projects outside the Policy’s scope include, but are not limited to, those that do not meet the criteria in the above examples and involve: XInstrument calibration exercises. XStatistical or technical methods development.

8. Genomic Data Sharing Plan (GDSP) Purpose of the GDSP Dataset value for use in secondary analyses Costs and other resource issues pertaining to data deposition, management, or access needs ( e.g., the availability of appropriate public data repositories or other data sharing mechanisms) Compliance and utility tracking Clinical Trial GDSP should be submitted to at the time of IRB review and as approval is being made.  CCR PSO working on study amendments for open protocols Other Research The GDSP should be submitted prior to data generation.  Ongoing studies must submit a GDSP if data generated on or after August 31, 2015.

9. Institutional Certification (IC) An IC must accompany the submission of all human data to the dbGaP at the time of study registration Explicit informed consent for open access data sharing should be provided by research participants for studies depositing full genome sequence into open access, whether sample or data collection is prospective or retrospective Assures that the Institutional Review Board (IRB) reviewed the informed consent and protocol to assure that that data sharing is appropriate and identified any data use limitations that may exist based on the language found in the consent Clinical Trials IC memo(s) should be filled immediately following IRB approval Other Research IC memo(s) should be filled out prior to data generation

10. Requests for Exceptions to Data Sharing, contd. In rare cases, NCI will consider requests for an exception to usual data submission expectations. Submission of genomic data may be precluded by: – international laws; limitations in the original informed consents; concerns about harms to individuals or groups; or other cases where expectations for data submission cannot be met. Exception Requests: Investigators provide a justification for any data submission exceptions prior to data generation and include an alternative data sharing plan. The Exception Request form should be signed by – Branch Chief – GPA and/or IRB, if using a consent justification for exception – CCR Scientific Director Trans-NCI Data Sharing Working Group for a recommendation NCI Scientific Program Leaders (SPL) for a consensus recommendation NCI Director for approval and signature NIH Deputy Director for Intramural Research for approval and signature.

11. Requests for Exceptions to Data Sharing NCI uses the following criteria to assess exception requests: Impact of data sharing compliance on scientific merit Unique resource High value resource Regulatory considerations – Missing consent from patients Ethical considerations NIH data sharing exception precedents Is there an acceptable alternative data-sharing plan (ADSP)? – Impact of ADSP on data re-use – Impact of ADSP on data discoverability – Burden – Feasibility In all cases where an ADSP is determined to be appropriate, information on how to request access to data and a basic summary of the study and study data will be listed in dbGaP (or other appropriate data repository).

12. Infrastructure, Resources for CCR GDS Policy

13. Developing a Genomic Data Sharing Plan (GDSP) The GDSP outlines a PI’s plan for generating genomic data: sample size; data type; estimated timeline; repository Each project/protocol requires a separate GDSP Each project under an Omnibus protocol needs its own GDSP A GDSP SOP ( SOP-RPS-21 ) has been developed for CCR GDSP Submission Process Overview: PI completes and submits a GDSP to the GPA The SD, or their delegate, and GPA reviews GDSP

14. Developing a GDSP: An example The CCR GDS website: http://bit.ly/CCR_GDS

15. Registering a Clinical Study Institutional Certification (IC) : PIs are responsible for assuring, through an IC, that data have been collected with informed consent from participants and in accordance with federal regulations safeguarding participant privacy. A Clinical Study Registration SOP has been developed for CCR- RPS- 23. Clinical Study Registration Process Overview: – Before data generation On IRB approval develop a GDSP and submit to GPA and SD for approval After GDSP has been accepted, fill IC; sign; submit to GPA GPA reviews; forwards to SD for review SD reviews, signs and returns to PI with a copy to GPA Mail a signed copy of IC to PSO

16. Registering a Clinical Study contd. Clinical Study Registration Process Overview: – After data generation/QC/cleaning Contact GPA with a request to register study in dbGaP. Attach a copy of IC. You must register your study even if you have been granted a data-sharing exception. GPA will send you: –dbGAP study configuration template –dbGAP Basic Study Information Sheet. Complete forms and mail back to GPA GPA will: –Ensure that forms are completely and accurately filled out –Register the study in the dbGAP portal –Invite PI to review the registered study and determine who will be the data submitter – PI or designee as assigned by the PI Once registration is complete, dbGaP will send PI an email invite to review study details After this you are ready to load your data into the SRA portal

17. Registering a Clinical Study: An example The CCR GDS website: http://bit.ly/CCR_GDS

18. Questions and Answers Genomic Program Administrator (GPA) Kathleen Calzone, PhD, RN, APNG, FAAN 301-435-0538, calzonek@mail.nih.gov GPA Administrator Anjan Purkayastha, PhD 301-594-1395, anjan.purkayastha@nih.gov

19. Scientific Director PI GPA/ GPA admin Protocol Support Office Fill. Email to GPA GDSP OK? YES. Email to SD NO. Email to PI with requested corrections Revise GDSP as per SD/GPA recommendations. Retain all versions for your records. Genomic Data Sharing Plan (GDSP) GDSP OK? YES. Sign. Email to GPA Retain copy for records. Email to PI Retain copy for records. Email to PSO Retain copy for records. NO. Send back to GPA Workflow for developing a GDSP for a Clinical Study

20. dbGaP PI GPA/GPA admin Scientific Director dbGAP docs OK? YES. Register study. Receive IRB approval. Develop GDSP. IC memo Fill and sign IC memo. Email GPA. Generate data. Complete QC. Email GPA. Request study registration. Attach signed IC memo. IC memo Sign. Return to PI. Signed IC memo Email PI dbGAP study docs dbGAP docs NO. Return w/ comments. Make edits. Email to GPA. dbGAP study Invite PI to review. Review dbGAP study. Work with GPA to make edits. Review and store IC memo. Fill. Email to GPA. Before data generation After data generation/QC Store. Email to PSO. Workflow for registering a Clinical Study Review. Send to SD IC memo