Determining the Primary Endpoint for a Stimulant Abuse Trial: Lessons Learned from STRIDE (CTN 0037)

Abstract

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.

• cocaine abuse
• endpoint
• exercise
• measurement
• stimulant abuse

Acknowledgements

This work is supported by the National Institute of Drug Abuse through the Clinical Trials Network for the Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study (U10 DA 02002405S2) PIs: B. Adinoff and M.H. Trivedi; Lead Investigator: M.H. Trivedi; NIDA K24 DA022412 (PI: E. Nunes); and NIDA U10 DA13035 (PI: E. Nunes).

Declaration of Interests

The authors alone are responsible for the content and writing of the paper and the paper has not been published or submitted elsewhere. Madhukar H. Trivedi, M.D. is a consultant to or on speaker bureaus for Abbott Laboratories, Inc.; Abdi Ibrahim; Akzo (Organon Pharmaceuticals, Inc.); AstraZeneca; Bristol-Myers Squibb Company; Cephalon, Inc.; Cyberonics, Inc.; Eli Lilly & Company; Evotec; Fabre Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products; LP; Johnson & Johnson PRD; Meade Johnson; Medtronic; Neuronetics; Otsuka Pharmaceuticals; Parke-Davis Pharmaceuticals, Inc.; Pfizer, Inc.; Sepracor; SHIRE Development; Solvay Pharmaceuticals; VantagePoint; and Wyeth-Ayerst Laboratories. He receives research support from the Agency for Healthcare Research and Quality (AHRQ); Corcept Therapeutics, Inc.; Cyberonics, Inc.; Merck; National Alliance for Research in Schizophrenia and Depression (NARSAD); National Institute of Mental Health; National Institute on Drug Abuse (NIDA); Novartis; Pharmacia & Upjohn; Predix Pharmaceuticals (Epix); Solvay Pharmaceuticals, Inc.; and Targacept.

Dr. T.L. Greer has received funding from NARSAD and an award from NIH.

Dr. J.S. Potter and Dr. E.V. Nunes have received funding from NIDA.

Dr. D. Warden has owned stock in Pfizer, Inc., and Bristol Meyers Squibb in the past 5 years and has received funding from NARSAD.

Dr. C. Rethorst, Mr. B.D. Grannemann and Ms. K.M. Ring have no interests to report. Dr. E. Somoza does not have any conflicts to report regarding the content of this submission.