Elements of Clinical Trial Quality Assurance

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

2. Monitor’s Responsibilities – ICH E6Section 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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).