Brookhaven Science Associates U.S. Department of Energy 1 Brookhaven National Laboratory Protocol Compliance Monitoring Darcy Mallon May 7, 2009

Brookhaven Science Associates U.S. Department of Energy 2 OUTLINE n Role of Research Subject Advocate (RSA) n Protocol Compliance Monitoring Plan

Brookhaven Science Associates U.S. Department of Energy 3 RESEARCH SUBJECT ADVOCATE n BNL is funded in part by a General Clinical Research Center (GCRC) grant through State University of Stony Brook at New York (SBU) n GCRC funding comes from the National Center for Research Resources (NCRR) n GCRC funded institutions are required to have a Research Subject Advocate (RSA)

Brookhaven Science Associates U.S. Department of Energy 4 RESEARCH SUBJECT ADVOCATE n The RSA is responsible for monitoring human subjects research activities and reporting corrective actions if deficiencies are found. n The RSA reviews active protocols and prepares reports that are sent to the Brookhaven National Laboratory (BNL) Clinical Research Quality Assurance Committee (CRQAC) and the SBU Institutional Review Board, the Committee on Research Involving Human Subjects (CORIHS) n All protocols are required to have a Data Safety Monitoring Plan (DSMP). Multicenter, high-risk and/or Phase III protocols are required to have a Data Safety Monitoring Board (DSMB).

Brookhaven Science Associates U.S. Department of Energy 5 PROTOCOL COMPLIANCE MONITORING n The RSA randomly selects a BNL protocol for review. n The scope of the Review will vary according to the safety issues that need to be addressed; however in most cases, a limited scope review of compliance with the Safety Plan will be performed. During the review, a protocol will be assessed for compliance with the following Safety Monitoring Plan parameters:

Brookhaven Science Associates U.S. Department of Energy 6 PROTOCOL COMPLIANCE MONITORING n Safety Tests & Measures: i) Screening labs, safety tests, examinations, and observations ii) Subject eligibility criteria iii) Adherence to the treatment plan n Adverse events i) Occurrence of adverse & serious adverse events ii) Categorization of AE’s n Adverse event reporting i) To Sponsor, IRB, FDA, and NIH, & GCRC n Aggregate Analysis of Adverse Events i) Use of stopping rules ii) Reporting of aggregate analysis & DSMB reports

Brookhaven Science Associates U.S. Department of Energy 7 PROTOCOL COMPLIANCE MONITORING n Study monitoring i) Frequency of monitoring ii) Reporting mechanism of study staff to PI n Documents to be reviewed in a review may include any of the following: i) Case Report Forms (CRFs) or Study Worksheets ii) Medical Records, Laboratory Results, &/or Shadow Files iii) Signed Consent Forms iv) Drug Accountability Documentation v) Screening Logs vi) Protocol, Amendments, and IRB Correspondence vii) Regulatory Binders and Documentation including IRB record

Brookhaven Science Associates U.S. Department of Energy 8 PROTOCOL COMPLIANCE MONITORING n Following the review, the RSA will discuss with the investigative team any issues or concerns that are discovered during the review. This will allow time for resolution of issues prior to the writing of the report. n A written report by the RSA will be prepared upon completion of the review. This report will contain the findings of the review and recommendations from the Office of RSA. Recommendations could include corrective actions that are required for major and minor deviations that were noted in the review and the possible need for follow- up reviews. The RSA will report results of review directly to the Investigator, CRQAC and CORIHS with recommendations for further action as necessary.

Brookhaven Science Associates U.S. Department of Energy 9 PROTOCOL COMPLIANCE MONITORING n All review reports will be kept confidential. The reports will only be shared with the PI, the CRQAC and CORIHS. Copies of review reports will be kept in a locked file cabinet in the Office of RSA and access will be limited to RSA staff. n Reviews will focus on compliance with the safety-monitoring plan but may address other issues that are raised in regards to safety. There are two types of reviews: “for cause” reviews and random reviews. The CRQAC or CORIHS may request a “for cause” review of a protocol as a result of known or suspected problems in the conduct of human subject research.

Brookhaven Science Associates U.S. Department of Energy 10 PROTOCOL COMPLIANCE MONITORING n Other reasons for review may be: A protocol considered to be potential high risk due to the phase or nature of study (phase I, gene transfer, complex), number of adverse events occurring (or potential for AEs), subject population to be enrolled (vulnerable subjects) or the protocol has been determined by CORIHS to have significant risk Protocols with limited oversight or monitoring such as a Principal Investigator as the sole monitor for a study, no medical monitor or DSMB involved in monitoring the study or junior investigators or inexperienced team members who may benefit from a QA Review. Protocols for which faculty, staff, or research participants have raised concerns.