Determining the primary endpoint for a stimulant abuse trial: lessons learned from STRIDE (CTN 0037).

Background: No consensus is available for identifying the best primary outcome for substance use disorder trials, making interpretation across trials difficult. Abstinence is the most desirable treatment outcome although a wide variety of other endpoints have been used.

Objectives: This report provides a framework for determining an optimal primary endpoint and the relevant measurement approach for substance use disorder treatment trials. The framework was developed based on a trial for stimulant abuse using exercise as an augmentation treatment, delivered within the NIDA Clinical Trials Network. The use of a common endpoint across trials will facilitate comparisons of treatment efficacy.

Methods: Primary endpoint options in existing substance abuse studies were evaluated. This evaluation included surveys of the literature for endpoints and measurement approaches, followed by assessment of endpoint choices against study design issues, population characteristics, tests of sensitivity, and tests of clinical meaningfulness.

Conclusion: We concluded that the best current choice for a primary endpoint is percent days abstinent, as measured by the Time Line Follow Back interview conducted three times a week with recall aided by a take-home Substance Use Diary. To improve the accuracy of the self-reported drug use, the results of qualitative urine drug screens will be used in conjunction with the Time Line Follow Back results.

Scientific Significance: There is a need for a standardized endpoint in this field to allow for comparison across treatment studies, and we suggest that the recommended candidate endpoint be considered. However, the study design and goals ultimately must guide the final decision.