1. MODULE I Close-Out Visit/Monitoring Reports Jane Fendl April 24, 2010 1Versions: Final 24-Apr-2010

2. Close-Out Visit (COV) Usually conducted when: All subjects have completed the study All queries are resolved Maybe conducted when: The sponsor or IRB decide to discontinue using a certain Investigator or site The sponsor decides to discontinue the study Investigator requests that the study be discontinued at the site. 2Versions: Final 24-Apr-2010

3. Preparing for the COV Schedule the visit Discuss with the Study Coordinator all tasks that must be completed Allow enough time to complete the visit in one trip Insure Investigator will be present Confirm visit with a letter that outlines all tasks that must be completed Before leaving the for the COV review: Site communication documents Previous monitoring visit reports and outstanding issues Query reports or requests Any information or issues requiring site notification 3Versions: Final 24-Apr-2010

4. Preparing for to the COV Protocol and amendments Instructions for returning or destroying investigational product Study specific requirements The Clinical Monitoring Plan Audit the Trial Master File 4Versions: Final 24-Apr-2010

5. Conducting the COV The CRA must: Sign the Site Visit Log Monitor the ICF for all subjects Monitor the CRFs Retrieve all remaining CRFs Monitor the Investigational product Prepare IP for return or destruction Total IP shipped – Total IP used = Total IP returned  If packaging IP for return, complete all necessary forms, pack the container, seal it and arrange for courier pick up. Container should be sealed in such a way that it is tamper proof. Do not leave IP for site tor return. 5Versions: Final 24-Apr-2010

6. Conducting the COV Monitor the Site Master File to ensure all regulatory (essential) documents are present Resolve outstanding queries Arrange time with CRC to resolve outstanding issues Review outstanding issues from previous visits 6Versions: Final 24-Apr-2010

7. Conducting the COV Meet with the Investigator & CRC to discuss: Any significant findings IRB notification Date of last subject and study completion Number of subjects screened, randomized, completed and withdrawn or dropped SAEs Records retention 2 years after last approval of marketing application or until there are no pending or contemplated marketing applications 2 years have elapsed since formal discontinuation of clinical development Location of records retention Notification of address change of site or records retention 7Versions: Final 24-Apr-2010

8. Conducting the COV Instructions for potential inspection Continued obligations ICH GCP Sponsor publication guidelines Financial disclosure requirements 8Versions: Final 24-Apr-2010

9. Items to Retrieve Copies of: The Subject Screening Log The Subject Enrollment Log Verify that all metrics are correct Copy of the Delegation of Authority Log Ensure that all delegated individuals are listed and that the form is up to date Copies of drug inventory/return records Tracking numbers for all shipments Randomization code envelopes if applicable CRFs and outstanding query forms 9Versions: Final 24-Apr-2010

10. After the COV Visit Write the report Write the follow up letter Evaluate the Investigator Enrollment of evaluable subjects Rate of enrollment GCP/ICH compliance IRB Protocol Adherence Staff performance Facilities Contract negotiation/budget Overall performance 10Versions: Final 24-Apr-2010