VHA Handbook 1058.01 Research Compliance Reporting Requirements HRPP 101 - September 30 2010

1. VHA Handbook 1058.01 Research Compliance Reporting Requirements HRPP 101 - September 30 2010

2. Highlights (New Requirements in Red – Previous Requirements in Blue) Requirements for Designation of Facility RCO [1058.01 §6c] Requirements to Conduct Annual and Triennial Audits as Specified by ORO [1058.01 §6c] Facility Director Reporting Requirements [1058.01 §6f] Annual Facility Director Certification of Research Oversight [1058.01 §6g] RCO Roles as Consultant to Review Committees [1058.01 §4t] Requires Reporting of All RCO Audit Findings to Relevant Review Committees and R&DC [1058.01 §§6d, 6e] Time Periods for Implementing Remedial Actions [1058.01 §5d] Requires Providing ORO Compliance Reports to ACOS/R, RCO, Relevant Review Committees and R&DC [1058.01 §6g]

3. Highlights (New Requirements in Red – Codification of Previous Guidance in Blue) Distinguishes Rapid Reporting Requirements for Serious Adverse Events and Unanticipated Problems Involving Risks to Subjects or Others from Reporting Requirements Under Local SOPs Clarifies Definitions of Serious or Continuing Noncompliance [1058.01 §§4e, 4x] Limits Special Rapid Reporting Requirements for Serious or Continuing Noncompliance to Human Research [1058.01 §§4e, 4x] Distinguishes Apparent Serious or Continuing Noncompliance from IRB-Determined Serious/Continuing Noncompliance and Provides Specific Examples[1058.01 §7i] Defines “Reportable Events” for Non-Human of Research [1058.01 §§8-11]

4. Role of the RCO RCO’s primary responsibility = auditing and reviewing research projects relative to VA research requirements RCO may also serve as a nonvoting consultant, as needed, to the facility’s R&D Committee, IRB, IACUC, Subcommittee on Research Safety (SRS), and other research review committees The RCO may not serve as a voting or nonvoting member of these committees -- may attend meetings of these committees when requested by the committee or as specified in local committee SOPs [1058.01 §4t]

5. Non-Voting Consultant vs Non-Voting Member • Real or Apparent Conflict of Interest • RCO audits entail review of IRB actions – the RCO’s perceived independence is compromised if the RCO is a member of the committee under review • Flexibility of RCO time and resource commitments • Multiple mandatory committee memberships decrease optimal use of RCO time and resources • Flexibility in developing working relationship that meet facility research protection and oversight needs [1058.01 §4t]

6. The IRB is responsible for determining: Whether or not apparent noncompliance is serious or continuing Remedial action(s) in response to identified noncompliance Verifying that the remediation is implemented as required. [1058.01 §7i]

7. Remedial Actions 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. [1058.01 §5d]

8. Serious or Continuing Noncompliance vs Apparent Serious or Continuing Noncompliance Serious Noncompliance: Involves substantive harm (or genuine risk of substantive harm) to the safety, rights, welfare of human subjects, research staff or others in human research Substantively compromises the effectiveness of the facility’s human research protection/oversight programs Continuing Noncompliance: Reflects a persistent failure to adhere to the laws, regulations, or policies governing VA human research [1058.01 §§4e,4x,7e, 7f, 7g]

9. Serious or Continuing Noncompliance vs Apparent Serious or Continuing Noncompliance Apparent Serious or Continuing Noncompliance = a situation that, in the judgment of the individual observing it: Satisfies the Handbook’s definition of Serious Noncompliance Satisfies the Handbook’s definition of Continuing Noncompliance Reflects one or more of the examples provided in the Handbook [1058.01 §§4e,4x,7e, 7f, 7g]

10. Apparent Serious or Continuing Noncompliance Observed by an RCO in an Informed Consent, Regulatory, or Other Systematic Audit of Human Subjects Research Must be reported to the Facility Director, IRB, ACOS/R, R&D Committee, etc. within 5 business days Facility Director must report to ORO Regional Office within 5 business days of being notified (even if disposition complete) Facility Director must provide follow-up reports as specified by ORO Regional Office Convened IRB determines whether: Serious or Continuing Noncompliance occurred Remedial Actions are warranted [1058.01 §7h]

11. Apparent Serious or Continuing Noncompliance in Human Subject Research Observed by anyone in the Research Community (including RCO in context other than audit) Must be reported to the IRB within 5 business days Convened IRB determines whether: Serious or Continuing Noncompliance occurred Remedial Actions are warranted If Serious of Continuing Noncompliance, IRB must report to Facility Director, ACOS/R, R&D Committee, etc, within 5 business days Facility Director must report to ORO Regional Office within 5 business days of being notified [1058.01 §7i]

12. Note Change in Reporting Requirements Involving • UNANTICIPATEDAdverse Events • UNANTICIPATED Problems Involving Risks to Subjects/Others The 5-day requirement for reporting Adverse Events (AEs) and Problems Involving Risks to Subjects or Others TO THE IRB Now applies only to AEs and Problems that are UNANTICIPATED and SERIOUS

13. “UNANTICIPATED” refers to an event/problem that is new or greater than previously known in terms of nature, severity, or frequency, given the procedures described in protocol-related documents and the characteristics of the study population. • “SERIOUS” refers to: • Events that qualify as Serious Adverse Events (SAEs) as defined by FDA;or • Problems/events that involve: • Substantive harm, or a genuine risk of substantive harm to the safety, rights, or welfare of research subjects, staff, or others; or • Substantively compromise the effectiveness of the facility’s human research protection or human research oversight programs

14. This change is meant to improve oversight by: • Decreasing the overload experienced by IRBs from rapidly reviewing large numbers of clinical events that are unlikely to reflect substantive, unconsidered risks • Allowing timely expert peer review focused on events that are more likely to reflect substantive concerns • All SAEs and Problems Involving Risks to Subjects or Others still require review by the IRB as described in local Standard Operating Procedures consistent with: • VHA Handbook 1200.05, • The Common Rule at 28 CFR 16, and • Applicable FDA regulations

15. Serious Adverse Event (SAE) Reporting Investigator (or other person) must report any localAE that is SERIOUS andUNANTICIPATED to the IRB within 5 business days: Serious = untoward physical or psychological occurrence in a human subject resulting in death, life-threatening experience, impatient hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or that requires medical, surgical, behavioral, social, or other intervention to prevent such an outcome Unanticipated = reflects a risk that is new or greater than previously known Special review by IRB (or qualified IRB member) within 5 business day after the report to categorize the event [1058.01 §§ 4b,4p,4x,4y,4bb,7c, 7d]

16. Serious Adverse Event (SAE) Reporting IRB must report any Unanticipated, Related, Local SAE to the Facility Director within 5 business days of categorization Related = event may reasonably be regarded as caused by, or as probably caused by, the research Facility Director must report to ORO Regional Office within 5 business days of being notified IRB (or qualified IRB member) must also document whether or not action is needed to prevent immediate hazard to subjects If consent or protocol modifications are required, convened IRB must determine whether previously enrolled subjects must be notified, and if so when, how, and how documented [1058.01 §§ 4b,4p,4x,4y,4bb,7c,7d]

17. Unanticipated Problem Reporting Investigator (or other person) must report any Unanticipated Problem Involving Risks to Subjects or Others in human research to the IRB within 5 business days if it: May reasonably be regarded to involve substantive harm, or a genuine risk of substantive, to safety, rights, or welfare, or Substantively compromises the effectiveness of the facility’s human research protection or human research oversight programs Special review by IRB (or qualified IRB member) required within 5 business days after the report to categorize the event Investigator (or other person) must report any other unanticipated problems involving risks to subjects or others in human research to the IRB promptly per local SOPs [1058.01 §§ 4y,4bb,7a,7b,7d]

18. Unanticipated Problem Reporting IRB must report Related, Serious, Unanticipated Problem Involving Risk to Subjects or Others to Facility Director within 5 business days of categorization Related = event may reasonably regarded as caused by, or as probably caused by, the research Facility Director must report to ORO Regional Office within 5 business days of being notified IRB (or qualified IRB member) must also document whether or not action is needed to prevent immediate hazard to subjects If consent or protocol modifications are required, convened IRB must determine whether previously enrolled subjects must be notified, and if so when, how, and how documented [1058.01 §§ 4b,4p,4x,4y,4bb,7c,7d]

19. Animal Research, Research Safety, Research Lab Security, Research Information Protection, Research Misconduct Reporting not based on “Serious or Continuing Noncompliance” as defined in human research Reportable Events defined for each type of research No special requirements for Rapid Review / Rapid Reporting to ORO 5-day standard for reporting: Reportable Event to Research Review Committee Review Committee Determination to Facility Director To ORO by Facility Director [1058.01 §§ 8, 9, 10, 11, 12]

20. Reportable Events for Animal Research Unanticipated Loss of Animal Life Animal theft or potentially dangerous escape Work-related / research-related injury requiring more than minor medical intervention, extended surveillance, or leading to serious complications or death Reportable incidents under applicable federal standards (examples provided) Noncompliance or deficiency that substantively compromises research animal protection of oversight programs Suspensions or terminations of research related to animal or human welfare; interruptions related to operational problems [1058.01 § 8]

21. Reportable Events for Research Safety Work-related / research-related injury, or exposure at greater than routine levels, requiring more than minor medical intervention, extended surveillance, or leading to serious complications or death Reportable incidents under applicable federal standards (examples provided) Noncompliance or deficiency that substantively compromises research safety oversight programs Research suspensions/terminations related to human welfare Unauthorized lab decommissions or reassignments requiring identification and disposal of hazardous/infectious materials [1058.01 § 9]

22. Reportable Events for Research Laboratory Security Injury or harm to any human being or lab animal related to break-in, security breach, or other security problem Any BSL-3 lab break-in or security breach Any break-in or security breach resulting in any loss of select agent or toxin or highly hazardous agent, substantial damage to the facility, or substantial loss of equipment/resources Noncompliance or deficiency that substantively compromises research laboratory security programs Research suspensions/terminations related to lab security External noncompliance findings [1058.01 § 10]

23. Reportable Events for Research Information Protection Report to ACOS/R, ISO, and Privacy Officer within 1 Hour Unauthorized access, use, disclosure, transmission, removal, theft, or loss related to research of VA Sensitive Information, including PHI, individually identifiable private information, or confidential information per Privacy Act, HIPAA, or Federal Records requirements Any NSOC-reportable incident Report within 5 business days Noncompliance or deficiency that substantively compromises research information protection programs Research suspensions/terminations for info protection concerns External noncompliance findings [1058.01 § 11]

24. Research Misconduct NOTIFY ORO CENTRAL OFFICE AS SOON AS POSSIBLE (BY TELEPHONE OR E-MAIL) ABOUT ANY ALLEGATIONS OF RESEARCH MISCONDUCT [1058.01 § 12]