Use of a relapse monitoring board: an independent assessment for determining relapse in clinical trials for bipolar disorder.

Objective: Independent review boards can provide an objective appraisal of investigators' decisions and may be useful for determining complex primary outcomes, such as bipolar disorder relapse, in crossnational studies. This article describes the use of an independent, blinded relapse monitoring board to assess the primary outcome (relapse) in an international clinical trial of risperidone long-acting therapy adjunctive to standard-care pharmacotherapy for patients with bipolar disorder.

Design: The fully autonomous relapse monitoring board was composed of a chair and two additional members-all psychiatrists and experts in the diagnostic, clinical, and therapeutic management of bipolar disorder. The relapse monitoring board met six times during the study to review patient relapse data and was charged with the responsibility of determining if the events described by investigators qualified as relapses. Additionally, the relapse monitoring board reviewed data for all randomized patients to identify any relapse events not recognized by investigators.

Results: Primary efficacy results were similar and significant for investigator- and relapse monitoring board-determined relapses. Ten discrepancies were noted: two of the 42 investigator-determined relapses did not meet the intended clinical relapse threshold as determined by the relapse monitoring board; conversely, the relapse monitoring board confirmed eight relapse events not identified by investigators. The relapse monitoring board had no direct interactions with patients and had to rely on the accuracy of investigator assessments. Also, once an investigator determined a relapse and the patients discontinued the study, less information was available to the relapse monitoring board for relapse assessment.

Conclusions: Use of the relapse monitoring board supported the validity of the study by incorporating a level of standardization to mitigate the risk that local practice in different cultures and medical systems at the sites would confound study results.