What defines a clinically meaningful outcome in the treatment of substance use disorders: reductions in direct consequences of drug use or improvement in overall functioning?

Abstract

Sustained abstinence is currently the only accepted end-point for pharmacotherapy trials for most substance use disorders (SUD), with the exception of alcohol. Despite recent efforts, the identification of a non-abstinence alternative as a clinically meaningful end-point for drug use trials has been elusive. The current standard for establishing a clinically meaningful outcome in SUD trials is to demonstrate that a reduction in drug use is associated with improvement in long-term functioning, but data indicate relatively weak associations between drug use and various psychosocial problem domains. This may be because assessments used most commonly to measure an individual's functioning do not specify whether aspects of functioning are a direct consequence of drug use. The acceptance of a non-abstinence-based end-point for alcohol use disorder trials was supported in part through associations with reductions in alcohol-related consequences, although measures designed to assess the direct consequences of drug use are rarely included in drug treatment efficacy trials. The field of substance use disorders should include measures of negative psychosocial and health consequences of drug use, as opposed to overall functioning, in the effort to establish meaningful non-abstinence-based end-points.