1. Common Mistakes & Audits 05/21/2014

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. 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?