Turkey: How to select a CRO and establish a long-term relationship?

1. Turkey: How to select a CRO and establish a long-term relationship? Edibe Taylan Medical & Public Affairs Director Sanofi-aventis,Turkey Vienna Conference on “Optimizing Clinical Trials in CEE-CIS Region” February 14th, 2008

2. Speech headlines • Background information on Clinical Research in Turkey • Outsourcing strategies • Turkish experience: Effective CRO management • Relationships with CROs/ one-time award vs long-term partnerships • A Best Practice from sanofi-aventis Turkey Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

3. Clinical research environment in Turkey • Increasing experience & participation in new clinical trials • Total investment by industry 15 m€1 • Total No of Clinical studies 316 2 • Number of CROs 9 3 • 4 local, 5 international • No of Clinical Research personnel ~200 • 2 key associations in the area • Turkish Association of Research Based Companies • Clinical Research Association 1Turkish Association of Research Based Companies survey_2006 2 www.clinicaltrials.gov 3 IKU Journal volume 16 Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

4. Number of clinical studies in TurkeyBy sponsor 316 www.clinicaltrials.gov Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

5. Number of clinical studies in Turkey Top 10 Pharmaceutical Company www.clinicaltrials.gov Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

6. There is a huge potential for clinical research in Turkey when compared to the population of other countries www.clinicaltrials.gov- January 15th, 2008 Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

7. Turkey has a competitive advantage in clinical research • Patient population • sufficient • esp naive patients • Legislation is present for a long time • 1993 Regulations on Pharmaceutical Research • 1995 Guideline on Good Clinical Practice • 2008 Guideline on Observational Studies • Investigators • high number • trained on GCP • experienced in multinational/multicenter trials • Investigative sites • can produce qualified data • are reputable internationally • have technical infrastructure • have local ethical committees Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

8. Sanofi-aventis is the leading company in Turkey with… • 60 projects are ongoing • in 250 clinical research sites • Total 40 s-a employee in clinical research both R&D team and affiliate team • Additional 13 FTE outsourced to CROs • Experienced in CRO management • Worked with 7 CROs • Partnership with only 1 CRO (namely Monitor) Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

9. Outsourcing in clinical research is a unique opportunity if the company… • has limited number of internal headcount • has limited expertise in some therapeutical areas • needs flexibility in providing headcount in a short time Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

10. …thus CROs are important players of the game by their services • Clinical Trial Management • Statistical planning/Analysis • Protocol,CRF etc design and writing • Final Study Report • Training partnership • Investigator Meeting organisation • Staff/Resource management Partial or full support in each item Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

11. A new study to be outsourced 1. CRO selection 2. Contract management 3. Study conduct 4. Close out S-a Turkey :CRO management phases 5. CRO evaluation Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

12. Calculate the resource needs Identify CROs for request for proposal Collect proposals (purchasing department) Negotiate the total cost (purchasing department) Send the final cost proposal to clinical research department Select CRO & document the reason (Clinical Operations) Inform CROs of the outcome (purchasing department) S-a Turkey: CRO selection steps Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

13. Meeting with CRO (presentation of the organization) Is the experience adequate? No Reevaluate the CRO next year during annual planning Yes Yes Yes Yes Start Request for proposal (RFP) Is the price within acceptable range (after negotiations)? No Reevaluate the CRO next year during annual planning Start working with a non-GCP study No Position as last option to work with a non-GCP study Is performance satisfactory? Continue working with a non-GCP study Organize system audit to CRO Continue working with a non-GCP study No Are the system audit results satisfactory? Consider organizing another system audit after 1 year Outsource a GCP study S-a Turkey: CRO Segmentation & Targetting decision making flow Repeat system audit every 3 years Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

14. Study conducted CRO selected End of projects Co-monitoring visits by s-a for CRO performance evalutions Closing meeting Weekly reports sent by CRO • organise a meeting • define tasks to be shared • prepare the contract accordingly • organise a meeting with Purchasing dept to review and document the performance of the CRO • according to the experience position the CRO (segmentation & targetting) • conduct regular CRO performance evaluations on site to ensure that the trial is monitored in compliance with the terms agreed upon • first immediately after the study initiation,at the close out visit and in between when necessary. S-a Turkey: CRO management Kick off meeting Training on company SOPs & protocol • nominate people according to the need for the study (CPL,CRA, CPA etc) • identify training needs • decide monitoring plan • define co-visit intervals • decide visit reporting CRO Management Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

15. A Best Practice for partnership : Sanofi-aventis Turkey & Monitor CRO • Sanofi-aventis started partnering with Monitor CRO 6 years ago. • Relationship established as a long-term partnership instead of one-time award. • Partnership sustained through cooperating in different projects. • Exponential growth achieved in 6 years for both partners • “speed, proactivity, synergy, harmonization, persistence, mission, transparency, empathy, success, trust, experience, friendship, responsibility, accountability, initiative, creativity…” characterizes this partnership. • Successful partnership resulted in a ‘’win-win’’ case. Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

16. Study conducted CRO selected End of projects Kick off meeting Training on company SOPs & protocol Co-monitoring visits by s-a for CRO Performance Evalutions Closing meeting Weekly reports sent by CRO Relationships with CROs: one-time award vs long-term partnerships Continuous feedback on the progress (both +/-) Quarterly meeting of Heads to evaluate team performance & communication Interim project management meetings, if there is a problem in patient recruitment Exchange of human resources in case of need or urgency (recruitment to and from CRO) Cooperation in diffferent projects CRO Partnership CRO Management Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

17. Limited HC & expertise in s-a Need for outsourcing Ambitious goal setting with in advance resource planning 2nd study: Confirmation of performance 1st study: Test • Great success achieved! • 4th country in patient recruitment among 52 • 2 successful audit reports • 2 sites in top 10 patient recruiting sites among 600 (2 awards) Basement for partnership EXCTRACT- TIMI 25 FLINT- ACT SYNERGY Exponential growth achieved in 6 years for both partners 22 projects ongoing Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

18. Partnership sustained through cooperating in different projects… • General Manager of Monitor CRO is the member of AkademiKA® Steering Committee • AkademiKA® is the GCP Training program sponsored by s-a • Flexible resource management • Career opportunity for CRAs of Monitor CRO in sanofi-aventis • Contracted clinical research personnel service provided by Monitor CRO to sanofi-aventis Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008

19. Successful partnership resulted in a ‘’win-win’’ case • Monitor has become a“full-service” CRO • Starting from protocol development to final study report preparation… • Sanofi-aventis “is the leading company in clinical research” in Turkey Edibe Taylan, Vienna Conference on ''Optimizing Clinical Trials in CEE-CIS Region''- 13-14 February 2008