Coordinating and monitoring multisite clinical trials that combine pharmacological and behavioral treatments.

OBJECTIVE: Coordination of a large, multicenter Phase 3 clinical trial is critical to the success of the trial. The focus of this article is to describe the special challenges involved in the coordination of the 11 clinical centers conducting the COMBINE clinical trial and to discuss the challenges of monitoring the information collected on the 1,383 participants enrolled in this trial. METHOD: The role of the coordinating center in working with the clinical sites is to ensure both high data quality and that the intervention protocol is conducted with appropriate attention paid to patient safety and consistency across sites. To satisfy those goals, a research committee of investigators and coordinating center staff was formed. The committee monitored adverse event reporting, participant safety, recruitment, delivery of the interventions, collection of assessments and completeness and timeliness of transfer of data to the coordinating center. Objective measures of performance were determined for each criterion to provide the principal investigators, study sponsor and Data and Safety Monitoring Board with feedback on conduct of the trial. Site performance as defined by these criteria was evaluated periodically, with both detailed written and verbal feedback provided to each investigator and study coordinator. RESULTS: The system was successful in detecting sites with performance issues, providing feedback to site personnel and measuring improvement. Study leadership, clinical center staff and coordinating center staff felt that the procedures for identifying and solving performance issues worked well and improved overall performance. CONCLUSIONS: Establishing an organizational structure that provided (1) leadership, (2) a venue for communication, (3) performance criteria and (4) a process for monitoring performance goals and providing feedback has enabled COMBINE to achieve success in reaching these markers of clinical trial practice.

Divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention.

This pilot study evaluates the safety and efficacy of divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention. Sixteen patients in moderate alcohol withdrawal were randomized to receive a standard benzodiazepine detoxification, depakote detoxification, or depakote detox plus maintenance. Symptom reduction occurred more rapidly and consistently in the depakote treated patients than in the benzodiazepine control group, and at six-week follow up a greater percentage of patients in the depakote maintenance group were completely abstinent than either detox-only group. There were no significant differences in sociodemographic or drinking data amongst the three cohort samples at baseline. Our findings suggest that the anticonvulsant divalproex sodium (Depakote) may be a safe and efficacious alternative to benzodiazepines for the treatment of alcohol withdrawal. It may be an advantageous alternative for outpatient detoxification, as it has no abuse potential, pharmacologic synergy with alcohol, or substantial cognitive or psychomotor side effects.