1. Enhancing the CRO-Sponsor Collaboration to Ensure High Quality of Clinical Data May 17,2011 | Beijing, China Charles Yan, PhD Shanghai Clinical Research Center

2. 2www.diahome.orgDrug Information Association Potential Advantages and Risks for Outsourcing Outsourcing for Clinical Data Management Considerations in Selecting a CRO Key Factors for High Data Quality Best Outsourcing Relationship Agenda

3. 3www.diahome.orgDrug Information Association Reduce: –Time to develop and commercialize a new drug –Sponsor’s fixed costs with personnel, equipment and facilities needed for its clinical development Provide: –Ready access to needed expertise and/or technology –Greater access to potential investigators –Knowledge of regulatory climate in foreign markets Potential Advantages for CROs

4. 4 Reduced control of the clinical trial process by the Sponsor –Delays in completion of studies –Lost or poor data quality –Regulatory infractions produce indirect consequences FDA regulations/GCPs Fraud and Abuse –IP Potential Risks of Outsourcing to CROs

5. 5www.diahome.orgDrug Information Association Data Management Plan CRF Design, Annotated CRF Database Setup and Edit Check Development Data Entry and Discrepancy Management Lab Data Management AE/SAE Management Coding (MedDRA + WHO DD) Database Locking QC and QA Outsourcing for Clinical Data Management Electronic Data Capture Site User Training, Administration and Support EDC ： Site Guides

6. 6www.diahome.orgDrug Information Association Company information – Historical overview of the organization, – Length of time in the industry, – Financial stability of the organization – Organizational structure Products and services Experience Product demonstration Commercial – Business sustainability – Cost of services Considerations in Selecting a CRO

7. 7www.diahome.orgDrug Information Association Compliance – Understanding of global regulations(FDA, SFDA, etc) – Archiving system – Quality systems and proof of compliance to their quality requirements – Quality assurance Documentation of system validation for regulated processes Evaluation of the vendor’s QC/QA process Disaster/contingency plan(s) to protect business operations Adaptation to sponsor’s SOPs Results of previous regulatory inspections Considerations in Selecting a CRO

8. 8www.diahome.orgDrug Information Association Capacity and Flexibility – Expansion with changing needs – Resources to deal with uncertainties – Handling additional assignments Capability and Credibility – Diversity of experience – Experienced people – Adequate facilities – Training and incentives for people Confidentiality Considerations in Selecting a CRO

9. 9www.diahome.orgDrug Information Association Documentation change control processes Review of required accreditation Personnel qualification, job descriptions, organizational charts, training plans etc. Data transfer process References from previous customers Outcomes of previous regulatory inspections Security of physical locations where services are provided (server rooms, file rooms, etc.) The number of sponsors or studies currently supported by the available CRO staff Considerations in Selecting a CRO

10. – Overview of the whole program – Ensure that processes for both companies are described in detail (SOPs and training) – Define the roles and responsibilities for sponsor and CRO – Discuss expectations of both teams in regard to deliverables, timelines and resource – Communication and decision-making strategy – Issue resolution process – Budget planning and management – Expectations and performance metrics 10 Key Factors for High Data Quality Detailed start-up meetings （ face-to-face ）

11. In recent industry survey, both Sponsor and CRO agree that the top sources of conflict are related to mismatched expectations. – Pharma: 88% agree – Service Providers: 92% agree 11www.diahome.orgDrug Information Association The Most Common Sources of Conflict For SponsorFor CRO Expected innovation does not materializeExpected volumes do not materialize Scope changes lead to additional costsChanges in requirements lead to increased & unrecoverable costs Off-contract purchasing undermines expected savings Customer does not provide committed resources Project delays due to supplierProject delays due to customer Quality problems Key Factors for High Data Quality

12. 12www.diahome.orgDrug Information Association Define Acceptable Metrics in Data Management （ Time, Cost, Quality and Quantity) Data Management ProcessKPI Study prepare phase—CRF design duration —Database setup duration Study conduct—CRF received->Data entry —Data entered -> query generated —Query generated-> query reviewed —Query resolution time —LPLV-> database lock Study closeout—Error Rate (data entry, CRF vs database) Key Factors for High Data Quality

13. To clearly define the roles and responsibilities for DM CRO 13www.diahome.orgDrug Information Association At Study Setup Phase Data Management Task DescriptionSponsorCRO Data Management Plan CRF Design and Annotated CRF Database Setup Validation Program CRF tracking Data Entry Discrepancy Management Coding (MedDRA or WHO DD or both)... Key Factors for High Data Quality

14. To have a good communication channels (weekly basis or as needed) 14www.diahome.orgDrug Information Association At Study Conduct Phase CROSponsor Report any findings during study conductDecision maker on any issues reported Or approval for the actions Submit weekly progress report ―Summary data quality ―CRF pages received ―CRF pages entered/cleaned ―Missing and/or expected CRFs ―Queries sent/outstanding/resolved As reviewer ―Focus on QA or QC ―Safety and efficacy data Interim AnalysisTimeline Key Factors for High Data Quality

15. To follow database lock procedures and to lock database on time 15www.diahome.orgDrug Information Association At Study Closeout Phase CROSponsor Database lockTimeline for Database lock Prepare DB lock checklist ―All data entered ―Any open query ―SAE reconciliation ―Coding ―QC ―… —Special query handling —Data quality review —SAE reconciliation resolving —Database locking approval Lock database and dataset transferring Check all docs completed and signed ―Paper CRF ―Datasets ―DMP ―… Key Factors for High Data Quality

16. 16www.diahome.orgDrug Information Association Understand, learn and respect each other –Careful selection and detailed contract vital for a long term successful relationship –Sponsors need to carefully assess the requirements of CRO –CRO needs to understand expectations of sponsor –Mutual benefit from the relationship –Support from senior management Set measurable goals and objectives –Performance measurement and feedback –Periodic, formal and fact-based relationship –Progress review process in place Communications and conflict resolution process Feedback and evaluation Best Outsourcing Relationship

17. 17www.diahome.orgDrug Information Association Thank you! Q&A Contact info: chongchao.yan@scrcnet.org