Office of Research Oversight Update

1. Office of Research Oversight Update VA IRB Chair Meeting Baltimore, Maryland August 14-15, 2012 August 14, 2012

2. ORO Update – Topics for Discussion • The Challenges of “Collaborative Research” in VA – The Infamous “Interim Guidance” • Operations Activities that May Constitute Research – VHA Handbook 1058.05 • Frequent Questions about Reporting to ORO – VHA Handbook 1058.01 • Open Discussion and Q&A

3. Office of Research Oversight Update The Challenges of “Collaborative Research” in VA – The Infamous “Interim Guidance” August 14, 2012

4. Research Data Disclosures for Collaborative Studies • Challenges • Federal Records Retention Requirements • Privacy/Confidentiality Requirements • Privacy Act, HIPAA Privacy Rule, etc • Data Ownership Issues • VA Data Security Requirements • Dual Appointment Investigator Issues

5. Research Data Disclosures for Collaborative Studies • VA data are data collected: • By a VA investigator • On VA time • Under a protocol approved by the VA IRB of Record and the VA R&D Committee • Affiliate data are data collected: • By an affiliate investigator • On affiliate time • Under a protocol approved by the affiliate IRB

6. Research Data Disclosures for Collaborative Studies • The “collaborative” study should be implemented as a multi-site study with activities clearly defined for each site • Separation of VA activities/research from affiliate activities/research is critical for studies combining VA data with affiliate data • VA must retain copy of all data disclosed to the affiliate for the “collaborative” study

7. Research Data Disclosures for Collaborative Studies • Critical factors: • Data collection should typically take place at the VA site on VA time and at the affiliate/collaborator site on affiliate/collaborator time as separate activities that can be clearly distinguished by the IRB and the R&DC • The status “off-site” VA research taking place at an affiliate siteon VA time should be clarified through a written agreement with the affiliate addressing data ownership and responsibility for research-related injury • The R&D Committee must only approve the VA research

8. Research Data Disclosures for Collaborative Studies • Protocols, consent documents, and authorizations for both sites must include: • Use of data in a multi-site study combining VA data and affiliate data • Data will be disclosed to study Coordinating Center • Location of Coordinating Center

9. Research Data Disclosures for Collaborative Studies • For existing “collaborative” studies with a single “protocol,” ORO recommended: • Separation of VA vs Affiliate research at applicable continuing reviews occurring after December 31, 2011 • By appropriately amending the informed consent documents and HIPAA authorizations

10. Research Data Disclosures for Collaborative Studies • For new “collaborative” studies initially approved after December 31, 2011, ORO recommended: • Use of separate protocols for the VA research versus the affiliate research, or • Use of a single protocol that clearly separates the VA research from the Affiliate research

11. Research Data Disclosures for Collaborative Studies • In addition to informed consent documents and HIPAA authorizations, relevant areas of separation may include: • Recruitment procedures/strategies/advertisements • Research related procedures • Data collection/storage/uses/disclosures • VA researchers/personnel/staff • VA Clinics/Units/Labs/Locations involved • Results of VA ISO and PO reviews

12. Research Data Disclosures for Collaborative Studies • It may be necessary to develop an MOU with the collaborating affiliate and/or SOPs to ensure that the VA R&D Committee approves ONLY the VA research • In conducting compliance reviews, ORO will seek evidence of a good faith effort by VA facilities to separate VA research activities from affiliate research activities

13. December 2011 Implementation Update on Research Data Disclosures for Collaborative Studies • Evidence of a good faith effort may consist of: • Revised SOPs that describe the content and review procedures for protocols, informed consent documents, and HIPAA Authorizations that clearly separate VA research from affiliate research • Revised protocol applications and templates that incorporate the content and review procedures for protocols, informed consent documents, and HIPAA Authorizations that clearly separate VA research from affiliate research

14. Research Data Disclosures for Collaborative Studies • In conducting compliance reviews, ORO will make “Observations” and “Recommendations” based on the Interim Guidance and the Implementation Update • Sample SOPS and Protocol Application documents are available on ORO’s website at http://www.va.gov/ORO/Correspondence_and_Guidance.asp

15. Office of Research Oversight Update Operations Activities that May Constitute Research – VHA Handbook 1058.05 August 14, 2012

16. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Establishes procedures for determining whether a VHA operations activity constitutes research Operations Activities – • Administrative, financial, legal, quality assurance, quality improvement, and public health endeavors that are necessary to support VHA’s missions of delivering health care to the nation’s Veterans, conducting research and development, performing medical education, and contributing to national emergency response. • Operations activities may or may notconstituteresearch.

17. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Research – • A systematic investigation designed to develop or contribute to generalizable knowledge. Generalizable Knowledge(for purposes of this Handbook) – • Information that expands the knowledge base of a scientific discipline or scholarly field of study. • Thus, systematic investigations designed to produce information to expand the knowledge base of a scientific discipline or scholarly field of study constitute research.

18. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Operations Activities that ARE NOT Research – • Activities that are not designed to produce information that expands the knowledge base of a scientific discipline (or other scholarly field) do not constitute research. • An operations activity does not constitute research if both:  (1)The activity is designed and/or implemented for internal VA purposes (i.e., its findings are intended to be used by and within VA or by entities responsible for overseeing VA); and (2) The activity is not designed to produce information that expandsthe knowledge base of a scientific discipline (or other scholarly field).

19. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Examples of Non-Research Operations Activities – • Quality assessment and quality improvement activities designed for internal VA purposes, including routine data collection and analysis for operational monitoring, evaluation, and program improvement purposes • Specific QA/QI examples provided in §5b: • VA All Employee Survey (AES), Voice of VA Survey, etc. • Cardiac Assessment Reporting and Tracking System (CART) • External Peer Review Program (EPRP) • Home and Community Based Quality Care Initiative

20. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Examples of Non-Research Operations Activities – • Specific QA/QI examples provided in §5b (continued): • Inpatient Evaluation Center (IPEC) • Mental Health Program Evaluation Centers • National Center on Homelessness Among Veterans • Office of Suicide Prevention • System-wide Ongoing Assessment and Review Strategy (SOARS) • VA Surgical Quality Improvement Program (VASQIP) • VHA Quality Improvement Initiative (VQuIP) • Public Health Investigations

21. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Examples of Non-Research Operations Activities – • VHA system redesign activities, patient satisfaction surveys, case management and care coordination, policy and guideline development and related evaluation activities, benchmarking activities, etc. • Competence or qualification reviews of VA employees and health care professionals, provider and health plan performance evaluations; peer review; training and education; accreditation, licensing, and credentialing; Joint Commission visits and related activities.

22. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Examples of Non-Research Operations Activities – • Medical reviews, medical use evaluations (MUEs), legal analyses, auditing services, regulatory compliance programs, fraud and abuse detection, ORO reviews and investigation, Medical Inspector investigations and national assessments, OIG activities. • Business planning and development such as cost-management and planning analyses related to managing and operating an entity, business management and general administrative activities, and financial auditing. • Underwriting and similar activities

23. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Operations Activities that ARE Research – • Any operations activity whose conceptualization, plan, or implementation is supplemented or modified in order to produce information expanding the knowledge base of a scientific discipline or scholarly field of study. • Modifying or adding to an existing non-research activity to produce information expanding the knowledge base of a scientific discipline or scholarly field of study. • Analyzing non-research data in a different way to produce information expanding the knowledge base of a scientific discipline or scholarly field of study.

24. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Use of Operations Data for Research • Data collected for non-research operations may subsequently be accessed and used for research • If such data are accessed and analyzed differently in order to expand the knowledge base of a discipline (ie, contribute to generalizable knowledge), then this access and use constitutes research. • An activity designed as non-research operations becomes research if supplemented or modified in order to expand the knowledge base of a discipline.

25. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Activities that ARE ALWAYS Research – • Activities funded or otherwise supported as research by the Office of Research & Development (ORD) or any other entity. • Clinical investigations as defined under Food and Drug Administration (FDA) regulations

26. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Consideration of Design Characteristics • Non-research operations activities must use sound design characteristics (methodology) to ensure reliable outcomes to fulfill program requirements • Design (methodology) itself may not define research • Critical question = why was the design (methodology) used? • Solely to fulfill operations need = non-research • Contribute to generalizable knowledge = to expand the knowledge base of a discipline = research

27. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Activities that ARE ALMOST ALWAYS Research – • Activities using: • Double blind interventions • Placebo controls • Prospective patient-level randomization to clinical interventions not tailored to individual patient benefit Publication and Presentation of Findings DO NOT Themselves Define Research

28. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH When in doubt, CONSULT and DOCUMENT • ORO/ORD = Any activities where there is doubt • Program Office = Activities funded, mandated, managed, sponsored, or otherwise supported by a VHA Program Office or that use Program Office data • Network Director or designee = Non-Program Office activities conducted at the Network Level • Facility Director or designee = Non-Program Office activities conducted at the Facility Level

29. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Documentation Requirements • Publication (or presentation) of findings from non-research operations activities does not itself constitute research. • Publication in peer-reviewed journals of findings from non-research activities REQUIRES documentation prior to publication by • Relevant VHA Program Office if funded, mandated, managed, sponsored, or supported by a VHA Program Office or using Program Office data • Otherwise, designated Facility or Network official (depending on scope of project)

30. VHA Handbook 1058.05 - VHA OPERATIONS ACTIVITIES THAT MAY CONSTITUTE RESEARCH Documentation Requirements • Publication in non-peer-reviewed journals and professional presentations of findings from non-research activities DO NOT REQUIRE documentation prior to publication or presentation • Documentation is encouraged whenever there may be doubt or misunderstanding about the nature of the activity

31. VHA Handbook 1058.05 - Sample Format for Documentation of Non-Research Activities Title of Proposed Publication: Author Attestation  As an author of the publication referenced above (copy attached), I attest that the findings reported in the publication were not derived, in whole or in part, from activities constituting research as described in VHA Handbook 1058.05. Provide for each VA Author and Co-Author Author Signature: Date: Author Name: VA Duty Station: Signature of Designated Official: Date: Name Title: Program Office or Facility: Note: Each VA author and coauthor must retain a copy of the documentation for a minimum of 5 years after publication and in accordance with any applicable records retention schedules.

32. Office of Research Oversight Update Frequent Questions about Reporting to ORO – VHA Handbook 1058.01 August 14, 2012

33. VHA Handbook 1058.01 - Frequent Questions about Reporting to ORO:Implementation of Remedial Action (§5.d) • Remedial actions related to specific research projects should typically be completed within 90-120 days of the research review committee’s determination of noncompliance. • Except where remediation requires substantial renovation, fiscal expenditure, hiring, legal negotiations, or other extenuating circumstances, remedial actions related to programmatic noncompliance should typically be completed within 120-180 daysof the noncompliance determination. • Where completion of remedial actions extends beyond the periods described in the preceding subparagraphs, the facility must provide ORO with a written justification for the delay and an acceptable timeline for completion.

34. VHA Handbook 1058.01 - Frequent Questions about Reporting to ORO:Secure Transmission of Reports (§5.e) • Electronic transmissions of reports to ORO: • Must be encrypted in accordance with applicable requirements of the VA Office of Information and Technology. • Many reports need not be encrypted

35. VHA Handbook 1058.01 - Frequent Questions about Reporting to ORO: • Rapid Reporting to ORO (§7.d) • IRB Review of Serious Unanticipated Problems and Unanticipated Serious Adverse Events • Convened IRB or qualified IRB member must review within 5 business days • If the convened IRB or the qualified IRB member-reviewer determines that the problem or event is serious and unanticipated and related to the research, the IRB Chair or designee must notify ORO via telephone or e-mail within 48 hours and report the problem or event directly (without intermediaries) to the facility Director within 5 business days after the determination

36. VHA Handbook 1058.01 - Frequent Questions about Reporting to ORO: • Rapid Reporting (§7.d) • New Requirement: Ifserious, unanticipated and related,the IRB Chair or designee must notify ORO via telephone or e-mail within 48 hours • If serious, unanticipated, and related,the IRB or qualified IRB member must determine if immediate action is needed to avoid serious hazard to subjects • If serious, unanticipated, and related, the convened IRB must determine if protocol or informed consent modifications are warranted, and if so • Whether previously enrolled subjects must be notified • How notification must be documented

37. VHA Handbook 1058.01 - Frequent Questions about Reporting to ORO: • Rapid Reporting (§4.d) • Related to the Research • Related to the research means an event or problem that may reasonably be regarded as caused by or probably caused by the research (see 21 CRF 312.64) • Before closing a case involving a unanticipated death in VA research, ORO must receive from the IRB a clear determination that the death • Wasor was notreasonably regarded as caused by or probably causedby the research, or • That such a determination is not possible (and why)

38. VHA Handbook 1058.01 - Frequent Questions about Reporting to ORO:Serious Noncompliance (§4.x) • Serious noncompliance • Failure to adhere to the laws regulations or policies governing human research that may reasonable be regarded as • Involving substantive hard, or a genuine risk of substantive harm, to the safety, rights, or welfare of human research subjects, research staff or others, or • Substantively compromising the effectiveness of a facility’s human research protection or human research oversight programs

39. VHA Handbook 1058.01 - Frequent Questions about Reporting to ORO:Serious Noncompliance (§7.f) • Examples of Apparent Serious Noncompliance • Participation by a research team member in the conduct of an active protocol without required credentialing, privileging, or scope of practice or engaging in activities outside the approved scope of practice • Continuation of interactions or interventions with human subjects beyond the specified IRB approval period • Implementation of substantive protocol changes without IRB approval (except to avoid immediate hazard to a subject) • Lack of required CRADO waiver for research involving children, prisoners, or international sites

40. VHA Handbook 1058.01 - Frequent Questions about Reporting to ORO:Serious Noncompliance (§7.f) • Examples of Apparent Serious Noncompliance • Individual or programmatic noncompliance involving substantive hard, or genuine risk of substantive harm, to the safety, rights, or welfare of human subjects, research staff, or others • Individual or programmatic noncompliance substantively compromising the effectiveness of human research protection or oversight program • Lack of quorum or inappropriately constituted IRB • Failure to document criteria for approval of waivers

41. VHA Handbook 1058.01 - Frequent Questions about Reporting to ORO:Continuing Noncompliance (§4.e & §7.g ) • Continuing Noncompliance • Persistent failure to adhere to the laws regulations or policies governing human research • Examples of Apparent Continuing Noncompliance • Failure to implement IRB-required changes to an ongoing protocol within the time period specified by the IRB • Deficiencies in informed consent or HIPAA authorization for 10 or more subjects • Failure to maintain documentation required by the IRB or the IRB-approved protocol • Failure to implement remedial actions as required by ORO

42. VHA Handbook 1058.01 - Frequent Questions about Reporting to ORO:IRB Review of Serious/Continuing Noncompliance (§7.i) • Reports must be reviewed a next convened meeting • IRB determines whether the reportedapparentserious or continuing noncompliance actually constituted serious or continuing noncompliance • IRB should document rationale for determinations • IRB determination of serious or continuing noncompliance must be reported to Facility Director within 5 business days of determination • Facility Director must report to ORO within 5 days after notification (unless already reported to ORO as identified by an RCO audit) - even if the IRB determination is preliminary or has been resolved with the 5-day reporting period

43. Research Data Disclosures for Collaborative Studies • Decision Charts on ORO SharePoint site at: http://vaww.vha.vaco.portal.va.gov/sites/ORO/RCO/Memoranda%20and%20Clarifications/Forms/AllItems.aspx http://www.va.gov/ORO/Docs/Guidance/1058_01_RCRR_NCOMP_Chart_12_01_2011.pdf http://www.va.gov/ORO/Docs/Guidance/VHA_1058_01_RCRR_SAE_URP_Chart_12_19_2011.pdf

44. Office of Research Oversight Update Open Discussion and Q&A August 14, 2012