Endpoints for Pharmacotherapy Trials for Alcohol Use Disorder.

Abstract

Alcohol use disorder (AUD) is a debilitating disorder, yet currently approved pharmacotherapies to treat AUD are under-utilized. The three medications approved by the US Food and Drug Administration (FDA) for the indication of AUD are disulfiram, acamprosate, and naltrexone. The current landscape of pharmacotherapies for AUD suggests opportunities for improvement. Clinical trials investigating novel pharmacotherapies for AUD traditionally use abstinence-based drinking outcomes or no heavy drinking days as trial endpoints to determine the efficacy of pharmacotherapies. These outcomes are typically measured through patient self-report endorsements of their drinking. Apart from these traditional outcomes, there have been recent developments in novel endpoints for AUD pharmacotherapies. These novel endpoints include utilizing the World Health Organization (WHO) risk drinking level reductions to promote a harm-reduction endpoint rather than an abstinence-based endpoint. Additionally, in contrast to patient self-report measurements, biological markers of alcohol use may serve as objective endpoints in AUD pharmacotherapy trials. Lastly, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) definition of recovery from AUD and patient-oriented outcomes offer new frameworks to consider endpoints associated with more than alcohol consumption itself, such as the provider-patient experiences with novel pharmacotherapies. These recent developments in new endpoints for AUD pharmacotherapies offer promising future opportunities for pharmacotherapy development, so long as validity and reliability measures are demonstrated for the endpoints. A greater breadth of endpoint utilization may better capture the complexity of AUD symptomatology.