Audit

1. Audit Ebru Mutlu-Omega CRO

2. General Purpose • to help quality (to maintain quality at present) • to assure quality (make sure that quality in future is maintained)

3. Who conduct audits? • Sponsor • Regulatory Authorities (FDA, EMEA or MOH )

4. If a clinical trial is being monitored what’s the point of auditing it?

5. Purpose of sponsor audits • ensure that sponsor meets regulatory and GCP requirements • ensure that SOPs are followed • ensure that the Investigator is following the protocol • ensure that the Investigator meets regulatory and GCP requirements

6. Auditors • are independent of and seperate from routine monitoring and quality control functions • qualified by training and exprience • qualifications should be documented

7. What type of audit? Investigator site CRO Systems (AE reporting) Audits Database Trial report Sponsor

8. Which studies? • all?? • pivotal phase II • pivotal phase III • CROs

9. General Criteria for audits • importance of trial to regulatory submission • number of subjects in trial • type and complexity of the trial • level of risks to trial subjects • indentified problems

10. Which centers? • random selection • high recruiters • low recruiters • for cause • preapare for regulatory inspection

11. When to audit an investigator site? • before recruitment • after recruitment • during recruitment • during follow-up • after study has completed

12. Timetable • letter (including sites selected for audit) • in-house general study file audit • in-house investigator file audit • pre-field audit discussions with monitor • field audit • field audit discussions with monitor • field audit discussions with investigator,study staff and monitor • audit report • follow-up action as appropriate

13. What auditors look for? • a complete, legible,visible and robust data trail • the requirements of GCP are being met

14. Top ten audit findings • informed consent (not all elements 53%) • non-adherance to protocol 30% • source documents and CRF entries (inadequate/inaccurate record 25%) • drug accountability (inadequate accountability 20%) • IRB documentation (problems 12%) • documentation and filling • patient compliance • AE reporting • SAE reporting • laboratory documentation

15. Specific audit findings • Documentation and filling • inadequate • miss-filling • Informed consent • patient’s signature not dated personally • incorrect version of form used • form not signed by the patient prior to study-related procedures performed • back dated signatures on form

16. Specific audit findings • Drug accountability • irregular inventory • incomplete or missing • receipts not signed by sites • CRFs not up to date • Laboratory • certification of accreditation • methodology description

17. What happens after audit? • audit report is issued.Draft???

25. What happens after audit? • sponsor and investigator responsible for auctioning recommendations • audit report to be filed (where) • audit certificate (who)

26. Regulatory inspections • FDA • Between 1977-1994 • 3000 routine • 650 for cause

27. Benefits • reassurance • opportunities to learn and raise standarts • opportunities for process improvement • helps keep us on course for regulatory/gcp compliance • helps maintain same standarts of quality across different projects(countries) • reduces possibility of delays in licensing and marketing of a drug • highlights areas where we need to take corrective actions • highlights training needs

28. Your site is being audited!!!!! • site contacted from goverment, regulatory authority, sponsor or cro or you are notified before the site is notified • verify and ensure regulatory department and project team is aware • rewiew of in-house files- obtain any deficient documents • review site’s regulatory binder-at site or over phone with site personnel • ensure any follow-up items from monitoring reports are completed

29. Your monitoring has been per ICH/GCP’s and your company SOP’s..... SO THERE IS NOTHING TO FEAR