Toward empirical identification of a clinically meaningful indicator of treatment outcome: Features of candidate indicators and evaluation of sensitivity to treatment effects and relationship to one year follow up cocaine use outcomes

Abstract

Background Selection of an appropriate indictor of treatment response in clinical trials is complex, particularly for the various illicit drugs of abuse. Most widely-used indicators have been selected based on expert group recommendation or convention rather than systematic empirical evaluation. Absence of an evidence-based, clinically meaningful index of treatment outcome hinders cross-study evaluations necessary for progress in addiction treatment science. Method Fifteen candidate indicators used in multiple clinical trials as well as some proposed recently are identified and discussed in terms of relative strengths and weaknesses (practicality, cost, verifiability, sensitivity to missing data). Using pooled data from five randomized controlled trials of cocaine dependence (N = 434), the indicators were compared in terms of sensitivity to the effects of treatment and relationship to cocaine use and general functioning during follow-up. Results Commonly used outcome measures (percent negative urine screens; percent days of abstinence) performed relatively well in that they were sensitive to the effects of the therapies evaluated. Others, including complete abstinence and reduction in frequency of use, were less sensitive to effects of specific therapies and were very weakly related to cocaine use or functioning during follow-up. Indicators more strongly related to cocaine use during follow-up were those that reflected achievement of sustained periods of abstinence, particularly at the end of treatment. Conclusions These analyses did not demonstrate overwhelming superiority of any single indicator, but did identify several that performed particularly poorly. Candidates for elimination included retention, complete abstinence, and indicators of reduced frequency of cocaine use.

Neurofunctional Reward Processing Changes in Cocaine Dependence During Recovery

“…Rather than one single measure, multiple outcome indicators have been identified as clinically meaningful (Carroll et al, 2014); here we present negative urine screens as our primary abstinence indicator. Negative urine screens comprise an objective measure of abstinence that has been identified in a recent review as a clinically meaningful indicator of treatment outcome (Carroll et al, 2014).…”

“…Negative urine screens comprise an objective measure of abstinence that has been identified in a recent review as a clinically meaningful indicator of treatment outcome (Carroll et al, 2014). Urine toxicology screens were obtained three times weekly during treatment and at each follow-up interview.…”

“…Given the importance of the VS in drug and reward processing, this area was selected as a region of interest (ROI) to examine relationships with abstinence indicators. Abstinence often occurs incrementally, rather than as a dichotomous process (Konova et al, 2013); negative urine screens are an objective measure of abstinence that has been identified as a clinically meaningful outcome indicator (Carroll et al, 2014). We hypothesized that pretreatmentposttreatment VS anticipatory changes would relate to negative urine screens.…”

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

“…Clinical trials of medications for managing cocaine use disorder have used a number of outcomes to indicate efficacy, but abstinence from cocaine use and retention in treatment have been used most frequently (for reviews, see Donovan et al, 2012;Carroll et al, 2014). Complete abstinence from cocaine use for a specified period of time during a clinical trial is frequently the primary outcome and is best verified with biochemical analysis (e.g., quantitative or qualitative urine testing for the cocaine metabolite benzoylecgonine).…”

“…Retention in treatment is usually defined as patient attendance at scheduled clinic visits and/or time to dropout from a protocol. Retention does not directly measure the traditional primary variable of interest (drug use), but it is linked to improved treatment outcome (Simpson et al, 1999;Ciraulo et al, 2003;Carroll et al, 2014).…”