Outcome Measures in Medication Trials for Substance Use Disorders

There are multiple therapeutic options to treat tobacco (e.g., nicotine replacement therapies, varenicline) and alcohol (e.g., naltrexone, acamprosate) use disorders. In contrast, there are currently no FDA-approved pharmacotherapies to treat stimulant (e.g., cocaine, methamphetamine) use disorders. Based on a commentary published by FDA staff, a period of sustained abstinence appears required for regulatory approval of a first-in-class medication to treat stimulant use disorders. Certainly, achieving abstinence remains the goal of treatment in both real world medical practice and clinical trials. However, if a medication can help patients to significantly reduce stimulant use (short of achieving a sustained abstinence) while attempting to quit, such reductions could confer meaningful benefit. The FDA has adopted the “percentage of subjects with no heavy drinking days” as an endpoint for pharmacotherapy trials in alcohol use disorders; this suggests there may be a potential path forward for developing analogous, non-abstinence endpoints for stimulant use disorder trials. However, reductions in drug use per se (short of abstinence) must have prognostic value in order to be considered an acceptable basis for FDA approval. Thus, even if a medication can provide sustained reductions in drug use, the challenge ahead is to demonstrate that this “success” is accompanied by benefits that accrue in dimensions readily understood by patients and their families, and of sufficient value to be reimbursed by third party payers. Emerging data sets discussed in this paper indicate that endpoints other than abstinence may ultimately be validated as outcome measures in pharmacotherapy trials for stimulant use disorders.