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. 2019 Jan;114(1):9-15.
doi: 10.1111/add.14289. Epub 2018 Jun 27.

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?

Brian D Kiluk  1 , Garrett M Fitzmaurice  2   3 , Eric C Strain  4 , Roger D Weiss  2   5
Affiliations

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?

Brian D Kiluk et al. Addiction. 2019 Jan.

Abstract

Background: 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.

Argument and analysis: 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.

Conclusions: 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.

Keywords: Addiction severity index; clinically meaningful outcome; functioning; inventory of drug use consequences; negative consequences; substance use disorders; treatment end-point.

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Conflict of interest statement

Declaration of interest: The topic for this manuscript was generated from discussion at a meeting held at the US Food and Drug Administration (FDA) offices in October 2016 that was sponsored by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) public-private partnership with the FDA. Authors of this article who attended the meeting (Kiluk, Fitzmaurice, Strain) received travel stipends and hotel accommodations provided by ACTTION. ACTTION has received research contracts, grants, or other revenue from the FDA, multiple pharmaceutical and device companies, philanthropy, and other sources. No official endorsement by the US FDA, US National Institutes of Health, or the pharmaceutical and device companies that have provided unrestricted grants to support the activities of ACTTION should be inferred. Author RDW has served as a consultant to Indivior, Alkermes, GW Pharmaceuticals, Daiichi Sankyo, and Braeburn Pharmaceuticals. Author ECS has served as a consultant or served on advisory boards for Indivior, The Oak Group, Egalet Pharmaceuticals, Caron, Innocoll, and Pinney Associates, and has received research funding through his university from Alkermes. All opinions expressed and implied in this paper are solely those of ECS and do not represent or reflect the views of the Johns Hopkins University or the Johns Hopkins Health System.

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References

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