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1. February 26, 2008 Bradley Merrill Thompson Sponsor-CRO Relationships: Managing Risk

5. CROs v SMOs Sponsor Sponsor’s Agent (CRO) Researcher’sAgent (SMO) Research Site/ Investigator

12. Delegation of Authority to CRO Portion of Transfer of Obligations form: X Ensuring the FDA and all participating Investigators are promptly informed of significant new adverse effects or risks with respect to the Study Materials X Maintaining an effective IND with respect to the Study X Ensuring that the Study is conducted in accordance with the Protocol X Ensuring proper monitoring of the Study X Providing Investigators with the information they need to conduct the Study properly X Selecting qualified Investigators 212 CRF 312.50 General responsibilities of sponsors Transferred to CRO Maintained by Sponsor Sponsor Responsibility

22. Source: Thomson CenterWatch 2005 Survey of 612 Investigative Sites in the U.S. Factor Most Often Causing Study Delays United States

26. Metrics in a CRO Relationship CRO Engagement RFP and Due Diligence Contracting Execution of work Evaluation Metric Creation Key Performance Indicators Critical Success Factors Specific Performance Indicators Discussion Senior Committee Junior Committee Discussion Analysis Measurement Feedback & Adjustment Feedback Planning Metric Use

28. Example Metric Definition Table *All days specified are elapsed time Cuddigan & King Clinical data management system (CDMS) Clinical trial management system (CTMS) Data Source 5 days Average number of days from patient visit to lab data available in CDMS Visit data to lab data available in database 60 days (mean); 90 days (oncology) Number of days from final protocol approval by sponsor to first patient enrolled at first site Final protocol to first patient recruited Achievement of key project timelines Target * Definition Related Metrics KPI

29. Example Metric Definition Table, contd. *All days specified are elapsed time Cuddigan & King CTMS CDMS Data Source 21 days Number of days between database lock and final approval study report Database lock to final study report 5 days Number of days from LPLV at site to database locked Last patient last visit (LPLV) to database lock Target * Definition Related Metrics KPI

30. Example Metric Definition Table, contd. Cuddigan & King CTMS Percent of sites enrolled that recruits 1 subject within one month of initiation visit Percent of non-performing centers Data manager Number of database errors found on database audit/total number of data fields audited Database error rate Achievement of target quality standards Data Source Definition Related Metrics KPI

31. Example Metric Definition Table, contd. Cuddigan & King Finance Number of change orders approved after initial contract sign-off Number of change orders Finance Total project fees after final invoice paid, compared with initial contract value (includes pass-through costs) Final actual contract cost as percent of initial contract value Compliance with agreed contract value Data Source Definition Related Metrics KPI

32. Metrics in a CRO Relationship CRO Engagement RFP and Due Diligence Contracting Execution of work Evaluation Metric Creation Key Performance Indicators Critical Success Factors Specific Performance Indicators Discussion Senior Committee Junior Committee Discussion Analysis Measurement Feedback & Adjustment Feedback Planning Metric Use

36. Third party vendors (e.g., labs) SPONSOR SUBJECT FDA IRB** DSMB, MRC, etc CRO* INVESTIGATOR INSTITUTION/ CLINICAL SITE CTA Informed Consent 1572 CTA CTAs * Contracts on behalf of sponsor (donated by dotted line) ** May or may not be a written agreement - depends on whether IRB is commercial, local, centralized, etc Services Agreements Blue = CTA Orange = Service Agreement Green = Regulatory “agreement”

49. Preferred Provider Agreement Relationship Management Model—Joint Committees Thomis & Desai Project Team 1 Project Team 2 Project Team 3 Project Team 4 Governance/Steering Committee (VPs) Operational Committee (Directors)

58. Questions?