MODULE I Close-Out Visit/Monitoring Reports

1. MODULE IClose-Out Visit/Monitoring Reports Jane Fendl April 24, 2010 Versions: 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. Versions: 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 Versions: 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 Versions: 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. Versions: 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 Versions: 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• IRB notification • Date of last subject and study completion • Number of subjects screened, randomized, completed and withdrawn or dropped • SAEs • Records retention • 2 years after last approval of marketing application or until there are no pending or contemplated marketing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 Versions: Final 24-Apr-2010

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