Data and Safety Monitoring Boards in NIH Clinical Trials: Meeting Guidance, But Facing Some Issues

WHY WE DID THIS STUDY

A Data and Safety Monitoring Board (DSMB) is a committee of experts responsible for reviewing clinical trial data on an ongoing basis to ensure the safety of study subjects and validity and integrity of the data. Members should be independent, with no vested interest in a specific treatment. A DSMB reviews evidence of adverse events and interim treatment outcomes to recommend whether trials should be continued, altered, or terminated. To do so, a DSMB must have access to "unmasked" data during the course of a trial, meaning that members know which subjects are in which treatment group. This study seeks to determine the extent to which DSMBs met National Institutes of Health (NIH) guidance, identify any challenges to DSMB effectiveness, and contribute to the Office of Inspector General's body of work concerning clinical trials and human subject protections.

HOW WE DID THIS STUDY

We reviewed the extent to which DSMBs met NIH guidance and identified any challenges to their effectiveness. According to general NIH guidance, DSMBs (which are composed of relevant experts) should meet regularly to review interim trial data and make recommendations concerning the trials' continuation or termination. Our findings are based on the population of 44 NIH-funded Phase III multi-site clinical trials completed in 2009 and 2010 that entailed potential risk. We reviewed NIH guidance and DSMB policies; documentation regarding DSMB meetings, including membership rosters and recommendations; surveyed DSMB members and principal investigators; and interviewed NIH staff and DSMB stakeholders.

WHAT WE FOUND

DSMBs met general NIH guidance. They met regularly, and 91 percent of meetings resulted in a recommendation to NIH. DSMB members represented multiple disciplines and had significant experience. Most DSMB members identified themselves as either clinicians or as clinical trial experts. However, DSMBs face some issues. NIH participation in closed DSMB meetings diminishes the appearance of independence; not all Institutes and Centers (IC) policies reference DSMB access to unmasked data; and NIH faces challenges in recruiting and training DSMB members.

WHAT WE RECOMMEND

NIH should (1) direct ICs to articulate the circumstances in which IC staff should participate in DSMB meetings, (2) direct ICs to explicitly reference DSMB access to unmasked data in their DSMB policies, and (3) identify ways to recruit and train new DSMB members. NIH concurred with all three recommendations.