Policy Governing Independent Safety Monitors and Independent Data and Safety Monitoring Boards

(Version date: April 24, 2015)

Policy

The National Institute of Mental Health (NIMH) has developed the following policy to establish expectations for the monitoring of NIMH-supported clinical trials  by Independent Safety Monitors (ISMs) and/or independent Data and Safety Monitoring Boards (DSMBs) to assure the safety of research participants, regulatory compliance, and the data integrity.

Scope

This policy applies to NIMH-supported clinical trials that utilize an ISM or independent DSMB. The NIMH has published a Policy Governing the Monitoring of Clinical Trials and guidance on risk-based monitoring to assist with the determination of an appropriate level of monitoring for a given study. Further, the NIMH has published guidance on developing Data and Safety Monitoring Plans (DSMPs).

This policy does not take the place of Institutional Review Board (IRB) guidance, Food and Drug Administration (FDA) requirements, or specific NIH guidelines.

Roles and Membership

An Independent Safety Monitor (ISM) is an independent physician or other appropriate expert with relevant expertise whose primary responsibility is to provide independent monitoring of clinical trials. The ISM is distinctly separate from a study medical monitor’s role.

A Data and Safety Monitoring Board (DSMB) is an independent group of experts charged with reviewing study data for data quality and integrity, adherence to the protocol, participant safety, study conduct and progress, and making determinations regarding study continuations, modifications, and suspensions/terminations.  The DSMB must have at least three members including, at minimum, one content-related or therapeutic area expert and a biostatistician.

The monitoring responsibilities of the ISM and DSMB enhance, but do not replace, the monitoring responsibilities of the Principal Investigator (PI) and the IRB. The PI and study team retain responsibility for real-time clinical management of the study.

Independence

ISMs and DSMB members must be independent from any professional or financial conflict of interest (COI) with the research project and/or study investigators. Independence ensures that competing interests do not unduly influence the ISM or the DSMB and supports objectivity that enhances the safety of participants and the integrity of the trial data.  Potential ISMs and DSMB members will provide the NIMH with qualifications and a COI statement indicating that members have no direct involvement with the study or COI with the investigators conducting the study. The ISM and DSMB members may be affiliated with the investigator's institution or other participating sites, but cannot be a scientific collaborator or co-author, supervisor, mentor/mentee, subordinate of the investigators, or a member of the investigator’s institutional department within the last three years. ISM and DSMB fees are allowable per NIH Policies and must be consistent with Institutional Policies.

Responsibilities and Review

The ISM or DSMB must review the DSMP and study protocol prior to the enrollment of the first participant to establish a charter that clearly outlines what data points will be monitored, how the data will be monitored, and the monitoring schedule.  The ISM and/or DSMB review should include, at minimum: enrollment data, safety data, and data integrity.

For blinded studies, the ISM or DSMB may be blinded or unblinded to the intervention assignment, but must be able to be unblinded if needed.

Review Schedule and Monitoring Reports

The meeting/review schedule should be commensurate with the level of risk involved with the study, but should occur no less than once per year.  Additional reports may be requested and additional meetings may be called as needed to address issues regarding participant safety. Members of the investigative team may be present for the open portion of a meeting, but not for the closed deliberations or the vote to recommend continuation, suspension, or termination of the study.

The ISM or DSMB is expected to issue a monitoring report to the PI following each review/meeting. This report should include any significant actions taken and the final recommendation(s) with regard to the study’s continuation. These reports must be submitted to the NIMH Program staff in the annual progress report.

References

NIH Policy for Data and Safety Monitoring (NOT98-084 ), issued on June 10, 1998

Further Guidance on Data and Safety Monitoring for Phase I and Phase II Trials (NOT-OD-00-038 ), issued on June 5, 2000

NIH Guidance on Reporting Adverse Events to IRBs for NIH-supported Multicenter Clinical Trials (NOT99-107 ), issued on June 11, 1999

Office of Inspector General Report OEI-12-11-00070 , Data and Safety Monitoring Boards in NIH Clinical Trials: Meeting Guidance, But Facing Some Issues