Common Mistakes & Audits

1. Common Mistakes & Audits

2. Summary of audit findings by category

3. Common Mistakes • Delegating responsibility rather than authority • The PI is always responsible for all study activity and for all personnel performance Lesson to be learned….PI Pick your sub-investigators and coordinators carefully!

4. Common Mistakes • Informed Consent This is the Achilles heel of research and is the most commonly cited in litigation

5. Common Mistakes • Not keeping the IRB informed of study changes and updates Especially in sponsored research we have a sponsor that continually monitors study activity- it is a common mistake to notify the sponsor of problems and forget to notify the IRB

6. Common TTUHSC Audit Findings • Discrepancies in executed Informed Consent Documents, such as: • Person signing as PI/Authorized Representative is not authorized to sign • PI/Authorized Representative fails to date • PI/Authorized Representative signature date different than Subject signature date • Most recent IRB-approved Informed Consent Document not utilized (old form is used)

7. Common TTUHSC Audit Findings

8. Common TTUHSC Audit Findings • Serious Adverse Events not reported to the IRB promptly (for example, SAE reporting to the IRB done months later at the request of the sponsor) • No source documentation available to verify that the subjects received a copy of the Informed Consent Document • Signed original Informed Consent Documents not consistently stored in the same location (for example, a majority of originals are found in the individual subject binders and a few originals are found in the medical record) • Investigators and/or research staff lacking TTUHSC human research protection training and/or HIPAA for Researchers training • Failure to submit amendments to the IRB regarding protocol modifications or changes in investigators and research staff

9. Common TTUHSC Audit Findings • Subject reimbursement procedures. • Non-research staff involved in the research process.

10. Sponsor Audits • Purpose: to evaluate trial conduct and compliance with the protocol, SOPs, GCP, and applicable regulations • A sponsor’s audit is independent and separate from routine monitoring or quality control functions • Should be done by individuals who are independent of the clinical trials/systems-regular Monitor can’t do them.

11. FDA Audits • Purpose: To ensure compliance Type of Audits • Study-directed audits • Investigator-directed audits • For cause audits • Not for cause audits-routine surveillance

12. What FDA Looks For • Who did what • Degree of delegation • Where study was performed • How/ where data were recorded • Drug accountability • Monitor contact & follow-up letters • Data audit FIRST binder they ask for may be correspondence!

13. Recent FDA Findings • Inclusion of individuals that did not meet the inclusion criteria. • Continuing of individuals that should have been removed from the study. • Study procedure errors (not following the study roadmap) • Errors in dosing • Communication errors

14. What if the FDA shows up? • Do NOT panic! • Ask for their ID and Form 482 • Give them ONLY what they specifically ask for • Try never to leave them alone • Put them in a room that has no other study materials • Be honest and helpful • Notify the Human Research Protection Office (HRPO) at TTUHSC-In advance if possible • Notify the study sponsor-in advance if possible

15. FDA Audits • FDA 482-Notice of Inspection (they’re coming) • FDA 483-Audit findings (BAD! Issued if they note some kind of problem, you may or may not get a warning (action) letter with it) • Establishment Inspection Report (EIR). This is an overall report of their visit-you’ll always get this. • Action Letters: NAI-No Action Indicated VAI-Voluntary action indicated OAI-Other action indicated

16. The Corrective Action Plan • PI MUST take responsibility • Do not play the Pass the Blame Game! • Address each issue directly • Enlist the help of your sponsor and local compliance team

17. FDA Regulatory Sanctions • Formal disqualification • Clinical hold • Voluntary restrictions • Criminal prosecution

18. Long-term consequences • Audit results are publicly accessible on the FDA website • Only bad conduct makes the news-front page • Most pre-study questionnaires from sponsors ask if you’ve ever been audited, received a 483. If you have they want a copy. • Effects your reputation in the clinical research arena • Your commitment & ethics may be questioned

19. Points to Remember • Audit Findings/Common Mistakes – The Informed Consent is most commonly cited in research litigation • The PI is always responsible for all study activity and for all personnel performance • Keep the IRB informed of all study changes and updates

20. QUESTIONS?