Making Non-Compliance Determinations

1. Making Non-Compliance Determinations Gerald Treiman, IRB Chair John Stillman, IRB Director Maureen Brinkman, IRB Administrator Ann Johnson, IRB Administrator

2. Introduction to Reporting • The Report Form is used to submit problems, events, and information to the IRB for review. • Examples of problems or events include the following: • Unexpected, related adverse events • Deviations • Adverse device effects • Breaches of confidentiality or privacy • Examples of information include the following: • DSMB reports • New information about the study that does not require and amendment • Complaints from participants • Warning or determination letters

3. The Report Review Process • There are 3 levels of review that may occur: • Administrative review – conducted by Maureen Brinkman • Starting point for all report forms EXCEPT adverse events • Subcommittee review – conducted by Ingrid Nygaard, Chris Stock, or Dennis O’Rourke • Starting point for adverse events • Convened board review

4. Report Form Determinations • Report forms are reviewed to make the following determinations • Unanticipated problems (UPs) • Non-compliance, not serious or continuing • Serious and/or continuing non-compliance • The administrative reviewer and subcommittee reviewer can make the following determinations: • The report is NOT a UP • The report is NOT non-compliance • The report is non-compliance, but not serious or continuing

5. Report Form Determinations • If the administrative reviewer or subcommittee reviewer believe the report is a UP or serious/continuing non-compliance, they forward it to the convened board. • Only the convened board can make the following determinations: • Unanticipated problems • Serious and/or continuing non-compliance

6. Non-Compliance Review Process • Can be initiated in the following ways: • The PI tells us there is a deviation via the report form • The IRB receives a complaint or other information that indicates there may be non-compliance • If the review process is initiated by a complaint/concern, the IRB conducts an inquiry to verify that there is evidence of non-compliance. This may include: • Interviews with study team members • Audits of study records • Collection of relevant data from other sources (e.g., OSP, FDA, Sponsor, etc.) • All inquires are conducted in cooperation with the PI. After all relevant information is collected and evidence of non-compliance is established, the PI submits a report form for review.

7. Definitions • Non-compliance: failure to abide by the policies, requirements, and determinations of the IRB, or federal rules and regulations including the requirements of the VHA Handbook 1200.05 governing human subject research. • Serious N0n-Compliance: An act or omission to act that resulted in increased physical, psychological, safety, or privacy risk that compromised the rights and welfare of research participants. • Continuing Non-Compliance: A pattern of repeated actions or omissions to act that suggests a future likelihood of reoccurrence and that indicates a deficiency in the ability or willingness to comply with federal regulations, VA [policy], requirements, and determinations of the IRB governing human subject research.

8. The Numbers: Since January 2008 Report forms submitted: 2,767 Admin Non-compliance Determinations: 448 Sub-C Non-compliance Determinations: 39 Serious/Continuing Non-compliance Determinations: 10

9. Protection of Research Participants It is the policy of the University of Utah IRB that before an administrative hold, suspension, or termination is put into effect the convened IRB or IRB designee considers whether any additional procedures need to be followed to protect the rights and welfare of current participants. These procedures may include but are not limited to: • Submitting a list of all currently enrolled participants including their status within the study; • Transferring participants to another investigator; • Making arrangements for clinical care outside the research; • Allowing continuation of some research activities under the supervision of an independent monitor; or • Requiring or permitting follow-up of participants for safety reasons.

10. Suspensions & Terminations • Suspension: A suspension of IRB approval is a directive of the convened IRB or IRB designee either to stop temporarily some or all previously approved research activities, or to stop permanently some previously approved research activities. Suspended protocols remain open and require continuing review. • Termination: A termination of IRB approval is a directive of the convened IRB or IRB designee to stop permanently all activities in a previously approved research protocol. Terminated protocols are considered closed and no longer require continuing review.

11. Reference Materials • IRB Website  Event Reporting • IRB Website  SOPs • 901: Unanticipated Problems Involving Risks to Participants and Others • 902: Protocol Deviations • 903: HRPP and Non-Compliance • 904: Administrative Hold, Suspension, and Termination of Approved Research • 905: Institutional Reporting Procedures • 906: Protection of Research Participants • 907: Research Complaints and Concerns • 908: Routine and For-Cause Audits • Board Reviewer Checklist  Report forms

12. Case Studies • Determinations/Decisions • Does the report represent serious non-compliance? • Does the report represent continuing non-compliance? • What are appropriate corrective actions? • These should take into account how participants should be handled in order to prevent further risk, based upon the situation. • Should the study be suspended or terminated?