1. QualityAssessment Clinical Research Compliance Office (CRCO)

2. QA activities include: • Auditing Not-for-cause For-cause • Federal Incident Reporting • Assistance to Investigators who hold an Investigational New Drug (IND) or Investigational Device Exemption (IDE)

3. What is auditing? • A systematic and independent examination of study related activities and documents to determine whether the • evaluated study related activities were conducted • data recorded, analyzed, and accurately reported according to the protocol • applicable standard operating procedures • good clinical practice • applicable regulatory requirements

4. Auditing vs. Monitoring Common use of these terms in human subjects research is that auditingis more random “spot checks” that are less frequent, whereas monitoringis usually more exhaustive and recurrent • Auditing is a type of monitoring • Types Common Audits: • Internal Audit • Sponsor or Sponsor Designee Audit • Federal Agency Audit • IU Research Compliance Audit

5. Internal, Sponsor, Federal Agency Audits • CRCO should be notified in the event of a sponsor or federal agency audit and provides assistance in: developing internal audit plans providing auditing tools preparing for a federal audit responding to audit findings* *including development of a corrective and preventive plan

6. IU Research Compliance Audits: Primary Goals • Monitor the conduct of the research • Assure the rights and welfare of human research participants are protected • Optimize compliance to federal regulations, state laws, and institutional policies • Ensure that human subjects research conducted at or on behalf of IU and its affiliates is of the highest quality and meets all applicable federal regulations, state laws, and institutional policies Researchers can view Auditors as a partner in ensuring a high state of regulatory compliance and agency inspection readiness. (IU Standard Operating Procedures for Research Involving Human Subjects: Auditing Human Subjects Research)

7. IU Research Compliance Audits • Conducted by the Human Subjects Research Auditors • Conducted in accordance with the IU Standard Operating Procedures for Auditing Human Subjects Research • Categorized as either scheduled (not-for-cause) or directed (for-cause)

8. IU Research Compliance Audits • Directed = An audit conducted in response to a directive by the Director of the Human Research Protection Program, Executive Director of Research Compliance, IRBs, or IRB Chairs . *Primary intention is often specific to the origination of the audit request. Generally covers areas including consent, authorization, eligibility, study intervention, follow-up, adverse event tracking/reporting, and data quality. Secondary intention is often to be educational and preventative.

9. IU Research Compliance Audits • Scheduled = An audit conducted as part of the human subjects audit plan and schedule; an audit not due to a specific request as defined under “directed audit” *Intention is to be educational and preventive. Generally covers areas including consent, authorization, eligibility, study intervention, follow-up, adverse event tracking/reporting, and data quality

10. The Audit Process • Site notification: investigator(s) are notified that the audit needs to be conducted and details of when, where, who, and what are established • Site & auditor preparation: the time between notification and the visit should be used by both the site and the auditor to prepare for the visit.

11. The Audit Process • Site visit: • The auditor meets with appropriate members of the research team and is oriented to the research records and processes • The auditor conducts the review of the specified research records, conducts interviews of staff involved, and asks questions as they arise

12. The Audit Process • Site visit (cont.): • A closeout meeting with appropriate study staff is conducted where findings are presented by the auditor and discussed • An audit report is later sent to the site from the auditor at which time a response to any findings (including corrective and preventive plans) is generally required; for Research Compliance audits, the report including the investigator response is submitted to the IRB for review

13. IU Research Compliance Audits: Common Findings • Use of wrong version of consent documents often due to insufficient system of tracking or distributing the most current version • Incomplete or inaccurate completion of the ‘Authorization for Release of Health Information for Research’ form • Documents used for source documentation that are not signed and dated by the original observer/recorder • Not listing all appropriate co-investigators on the investigator list

14. IU Research Compliance Audits: Common Findings • Inconsistency in completion of regulatory documents—this happens most often when documents are amended but all of the documents that should be updated are not (e.g. updates to the protocol without changing the SSS or IC) • Also, inconsistency between the IRB approved documents and actual practice • Lack of documentation of the informed consent process • Lack of documentation of the PI’s review of protocol deviations to determine whether the deviations require prompt reporting according to IU SOP for Unanticipated Problems and Noncompliance

15. Federal Incident Reporting • Certain events that may occur during the course of conducting research, such as deviations from the IRB approved protocol, noncompliance with institutional policies, adverse events related to research participation are required to be reported to the IRB • When the IRB determines an event to meet the definition of serious and/or continuing noncompliance or an unanticipated problem involving risks to subjects or others (UPIRTSO), these events are required to be reported to certain federal agencies if the study is federally funded or is a clinical investigation involving an FDA regulated product • IRB imposed suspensions of these types of studies are also required to be reported • A CRCO staff member is present at all biomedical IRB meetings and assists in finalizing meeting minutes related to any reportable events • CRCO drafts and sends letters to federal agencies when required and responds to any inquiries regarding the reported events with assistance from HSO

16. IND/IDE Assistance • An IND Application is a request for authorization from the FDA to administer an investigational drug or biological product to humans • An IDE Application is a request for authorization from the FDA to use an investigational device that poses a significant risk to humans • Even when human subjects research involves drugs, biological products, and/or devices, the regulations allow some exemptions from the IND or IDE requirements • Once the FDA grants authorization or approval of an IND or IDE, the sponsor (often a pharmaceutical or device company) is responsible for following specific FDA regulations in relation to holding an IND or IDE • Although pharmaceutical and device companies often hold the IND or IDE for clinical trials, it is becoming more common for individual investigators to hold these (referred to as sponsor-investigators)

17. IND/IDE Assistance • CTSI provides assistance to IU investigators during the IND or IDE application process • Once an IND or IDE is obtained, CRCO provides education (required at IU) and resources to IU sponsor-investigators and their study teams • Resources include ongoing education, form templates and some monitoring of the research records