1. Elements of Clinical Trial Quality Assurance Regulatory Coordinator –SCTR SUCCESS Center QA Monitor – NIDA Clinical Trials Network Stephanie Gentilin, CCRA

2. Clinical Trials Network Monitor’s Responsibilities – ICH E6 Section 5.18 Overall Purpose of Monitoring  Verify the rights and well-being of human subjects are protected  Verify that reported trial data are accurate, complete and verifiable from source documents  Verify the study is conducted in compliance with the study protocol, GCP guidelines and applicable regulations

3. Clinical Trials Network Selection and Qualifications of Monitors Should be appointed by the sponsor Should be appropriately trained, and should have the scientific and/or clinical knowledge needed to monitor the trial adequately Should be thoroughly familiar with the investigational product(s), the protocol, consent and any other written information

4. Clinical Trials Network Monitor Responsibilities Act as main line of communication between the sponsor and investigator Follow sponsor SOPs for monitoring and protocol specific requirements Site-selection / Pre-study visit  Study-Mandated Criteria Investigator qualifications Facilities and Equipment  Basic Investigator Criteria Reputation / Access to Subjects / Concurrent studies

5. Clinical Trials Network Study Initiation Visit Detailed explanation of protocol  CRF review  AEs  Schedule of Events Verify regulatory approvals in place Assess supply inventory  Confirm labeling / organization of investigational product

6. Clinical Trials Network Routine / Interim Monitoring visits Investigator compliance  With protocol, regulations and GCP guidelines Check accuracy and completeness of CRFs and source against one another  Data are reported accurately  Modifications to the IP are well documented  AEs and concomitant medications reviewed  Withdrawals and dropouts reported  Consent obtained

7. Clinical Trials Network Routine / Interim Monitoring visits Evaluate study conduct  Review for protocol deviations and reporting  Review recruitment  Check supplies Factory influencing the rate of visits  Type of disease  Level of complicated medical condition  Complexity of study design  Previous performance

8. Clinical Trials Network Study Closeout Visit Collect CRFs  Outstanding corrections are made Ship and/or pick up all remaining clinical supplies Confirms regulatory files are complete Review record retention policies Clarify remaining sponsor commitments

9. Clinical Trials Network Monitoring Report Written report to sponsor after each site visit or trial-related communication. Should include:  Date of visit  Site  Name of monitor  Name of investigator and personnel contacted  Summary of information reviewed  Significant findings and corrective action plans Review and follow up on corrective actions should be documented

10. Clinical Trials Network Audits Independent of the clinical trials/systems Independent of and separate from routine monitoring or QC functions To evaluate trial conduct and compliance with protocol, SOPs, GCP and applicable regulatory requirements

11. Clinical Trials Network Auditing Procedures Should be conducted in accordance with Sponsor SOPs Based on:  Type and complexity of trial  Level of risk to the subject  Regulatory reporting requirements  Identified problems Audit findings should be documented When required by law, sponsor should provide an audit certificate

12. Clinical Trials Network Noncompliance Prompt action by sponsor should be taken to secure compliance If serious and/or persistent noncompliance on the part of an investigator/institution, the sponsor may terminate participation in the trial  Sponsor should promptly notify regulatory authority(ies).