1. How to audit the role of the vendor in the conduct of outsourced studies Kristel Van de Voorde Director Global Quality Regulatory Compliance Bristol-Myers Squibb

2. Agenda Scope Audit approaches Audit of the vendor quality system Examples of audit findings

3. 3 Scope Companies increase the level of outsourcing Outsourced aspects include –Study management –Study site monitoring –Central laboratories / bio imaging –IVRS systems –Data management –Safety data processing How to ensure adequate audit coverage?

4. 4 Audit approaches Audit a sample of selected investigator sites –Pro : systems are seen in operation –Con : what to conclude if one site is good and the other is not? Audit the quality system at the vendor –Pro : can assess the processes that are established to ensure quality –Con : avoid that assessment is only based on theory Audit the CRO oversight process at the sponsor –Selection process, contracts, task lists –Important to assess systems put in place for communication and oversight

5. 5 The audit approach ? A combination of all approaches Start with site audits to build your audit hypothesis Focus on integration of quality systems Focus on operational interfaces Determine best timing of the audit

6. 6 6 Audit of Quality System DOACT DOACTDOACT Sponsor oversight Services by vendor Investigator Auditing CHECK PLAN

7. 7 Audit of Vendor Quality System Audit the processes to detect failures What to assess for a monitoring vendor? –Monitor selection, geographical coverage, turnover and handover –Monitor training and SOPs –Monitoring contract, plan and other guidance –Early process controls –Oversight of other subcontractor performance How? –Investigator site audits : at least 3 sites –Vendor system audit

8. 8 Audit of Vendor Quality System Audit the processes to correct failures What to assess for a monitoring vendor? –Monitoring reports –Issue identification and actions taken, escalation –Communication to sponsor –Systems to react to increased needs for monitoring How? –Vendor system audit

9. 9 Audit of Vendor Quality System Audit the processes to prevent failures What to assess for a monitoring vendor? –Audit plans –Audit findings tracking and trending –Issue tracking and trending –Mechanisms to communicate issues with other vendors –Process improvement systems How? –Vendor system audit

10. 10 Audit of Vendor Quality System Audit the process for issue management What? –Definition and understanding of Significant protocol deviations Serious breach Serious and or persistent non-compliance Fraud –Ways to detect issues: Have quality metrics Assess facts

11. 11 Audit of Vendor Quality System Audit the process for issue management (2) What? –Who is informed / consulted –Process to react Joint directed audit Action plan with commitments Close follow-up –Responsibilities When is sponsor notified? Who is involved in the decision?

12. 12 Case 1 : vendors requiring interaction Case description : a global vendor was contracted for study management and other vendors for monitoring of the sites Deficiencies in the QM system: –Monitoring tools were not shared –Monitoring systems do not connect Lessons learned : verify that robust processes are in place to detect non-compliance

13. 13 Case 2 : vendor to provide oversight of another vendor Case description : a vendor responsible for study management was asked to track images for central evaluation by speciality vendor Deficiencies in the QM system: –No training of site staff, performing tests, was provided for –No feedback on early process control was returned to the sites Lessons learned : verify that robust processes are in place to prevent non-compliance

14. 14 Case 3 : esoteric lab Case description : a university lab was contracted to provide evaluation of the primary efficacy parameter Deficiencies in the QM system: –Methodologies not standardised across labs –Procedures not specific enough –Absence of software validation Lessons learned : verify that processes (SOPs, validation) are in place to ensure standardised approaches

15. 15 Case 4 :issue management and sponsor oversight Case description : site monitoring was outsourced Deficiencies in the QM system: –All protocol deviations were documented, reported, but no actions were taken –Vendor detected quality issues, sponsor decided on continuation of enrolment Lessons learned : verify that processes allow those that monitor the quality can make the appropriate decisions

16. 16 Conclusions Sponsor may delegate responsibilities, but stays ultimately responsible. Role of sponsor to be clarified. Situation complicates as the number of partners involved increases. Sponsor should be confident in quality control and quality assurance implemented by the vendor. Important is not to only identify what goes wrong, but to act appropriately in alignment between vendor and sponsor.

17. 17 Disclaimer The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. (“DIA”), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated. These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved. Drug Information Association, DIA and DIA logo are registered trademarks or trademarks of Drug Information Association Inc. All other trademarks are the property of their respective owners.