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? CRO Investigator site Systems (AE reporting) Trial report Sponsor Database Audits

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? 1. a complete, legible,visible and robust data trail 2. 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