Cocaine Rapid Efficacy Screening Trials (CREST): lessons learned.

Aims: The Cocaine Rapid Efficacy Screening Trials (CREST) were designed by the National Institute on Drug Abuse Division of Treatment Research and Development (NIDA, DT R&D) to rapidly screen a number of medications potentially useful for the treatment of cocaine dependence.
Design: Each CREST trial was designed to compare several medications in a single trial against an unmatched placebo. The placebo group was included in each trial to avoid the nearly universal positive response to medications seen in open-label trials. In addition, a common set of procedures and outcome measures were employed throughout to increase comparability of results obtained from different trials and from different times.
Participants: In all, 18 medications were screened in seven different trials, conducted in four different sites throughout the United States involving 398 cocaine-dependent patients.
Findings: Three medications were found to be promising enough to include in subsequent larger trials. Common statistical procedures for evaluating medications were developed to facilitate comparisons across sites and across time. A portion of the data were pooled and analyzed, which yielded some useful insights into cocaine dependence and its treatment. Finally, a review of individual trials together with the pooled analysis revealed several potential improvements for future screening trials.
Conclusions: Overall, the CREST trials proved to be useful for rapidly screening medications for treatment of cocaine dependence, but several modifications in design should be made before this framework is applied further.