Primary outcome indices in illicit drug dependence treatment research: Systematic approach to selection and measurement of drug use end-points in clinical trials

Alcohol and Drug Abuse Institute, University of Washington, Seattle, USA.
Addiction (Impact Factor: 4.74). 07/2011; 107(4):694-708. DOI: 10.1111/j.1360-0443.2011.03473.x
Source: PubMed


Clinical trials test the safety and efficacy of behavioral and pharmacological interventions in drug-dependent individuals. However, there is no consensus about the most appropriate outcome(s) to consider in determining treatment efficacy or on the most appropriate methods for assessing selected outcome(s). We summarize the discussion and recommendations of treatment and research experts, convened by the US National Institute on Drug Abuse, to select appropriate primary outcomes for drug dependence treatment clinical trials, and in particular the feasibility of selecting a common outcome to be included in all or most trials.
A brief history of outcomes employed in prior drug dependence treatment research, incorporating perspectives from tobacco and alcohol research, is included. The relative merits and limitations of focusing on drug-taking behavior, as measured by self-report and qualitative or quantitative biological markers, are evaluated.
Drug-taking behavior, measured ideally by a combination of self-report and biological indicators, is seen as the most appropriate proximal primary outcome in drug dependence treatment clinical trials.
We conclude that the most appropriate outcome will vary as a function of salient variables inherent in the clinical trial, such as the type of intervention, its target, treatment goals (e.g. abstinence or reduction of use) and the perspective being taken (e.g. researcher, clinical program, patient, society). It is recommended that a decision process, based on such trial variables, be developed to guide the selection of primary and secondary outcomes as well as the methods to assess them.

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Available from: Marilyn A Huestis, Oct 20, 2014
    • "In illicit drug use research, point-of-care drug urine tests capable of detecting use for two or more days are used to supplement self-report data (Donovan et al., 2012; Jatlow and O'Malley, 2010). A number of alcohol biomarkers detectable within urine samples are available to supplement self-report (Litten et al., 2010). "
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    ABSTRACT: Aims: This study investigated which ethyl glucuronide immunoassay (EtG-I) cutoff best detects heavy versus light drinking over five days in alcohol dependent outpatients. Methods: A total of 121 adults with alcohol use disorders and co-occurring psychiatric disorders took part in an alcohol treatment study. Participants provided self-reported drinking data and urine samples three times per week for 16-weeks (total samples=2761). Agreement between low (100ng/mL, 200ng/mL), and moderate (500ng/mL) EtG-I cutoffs and light (women ≤3 standard drinks, men ≤4 standard drinks) and heavy drinking (women >3, men >4 standard drinks) were calculated over one to five days. Results: The 100ng/mL cutoff detected >76% of light drinking for two days, and 66% at five days. The 100ng/mL cutoff detected 84% (1 day) to 79% (5 days) of heavy drinking. The 200ng/mL cutoff detected >55% of light drinking across five days and >66% of heavy drinking across five days. A 500ng/mL cutoff identified 68% of light drinking and 78% of heavy drinking for one day, with detection of light (2-5 days <58%) and heavy drinking (2-5 days <71%) decreasing thereafter. Relative to 100ng/mL, the 200ng/mL and 500ng/mL cutoffs were less likely to result in false positives. Conclusions: An EtG-I cutoff of 100ng/mL is most likely to detect heavy drinking for up to five days and any drinking during the previous two days. Cutoffs of ≥500ng/mL are likely to only detect heavy drinking during the previous day.
    Drug and alcohol dependence 10/2015; DOI:10.1016/j.drugalcdep.2015.10.004 · 3.42 Impact Factor
    • "A binary measure of no heavy drinking has been proposed as a primary end point in the Food and Drug Administration's draft guidance for AUD medications development (Food and Drug Administration, 2015), and the European Medicines Agency (2010) has approved reductions in heavy drinking as a primary end point for trials with harm reduction goals. Yet, there is still a lack of consensus among researchers in the field regarding the optimal outcome for treatment studies, and the selection of primary and secondary outcomes can depend on the goal of the trial (Donovan et al., 2012). We recommend that, when alcohol consumption is used as an outcome, information is provided on the use of biomarkers of alcohol use, which are commonly used to validate self-report data, along with the correspondence between the biomarker(s) and self-reported consumption measures (Litten et al., 2010). "
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    ABSTRACT: The primary goals in conducting clinical trials of treatments for alcohol use disorders (AUDs) are to identify efficacious treatments and determine which treatments are most efficacious for which patients. Accurate reporting of study design features and results is imperative to enable readers of research reports to evaluate to what extent a study has achieved these goals. Guidance on quality of clinical trial reporting has evolved substantially over the past 2 decades, primarily through the publication and widespread adoption of the Consolidated Standards of Reporting Trials statement. However, there is room to improve the adoption of those standards in reporting the design and findings of treatment trials for AUD. This paper provides a narrative review of guidance on reporting quality in AUD treatment trials. Despite improvements in the reporting of results of treatment trials for AUD over the past 2 decades, many published reports provide insufficient information on design or methods. The reporting of alcohol treatment trial design, analysis, and results requires improvement in 4 primary areas: (i) trial registration, (ii) procedures for recruitment and retention, (iii) procedures for randomization and intervention design considerations, and (iv) statistical methods used to assess treatment efficacy. Improvements in these areas and the adoption of reporting standards by authors, reviewers, and editors are critical to an accurate assessment of the reliability and validity of treatment effects. Continued developments in this area are needed to move AUD treatment research forward via systematic reviews and meta-analyses that maximize the utility of completed studies. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; 39(9). DOI:10.1111/acer.12797 · 3.21 Impact Factor
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    • "Results based on urine toxicology screens are among the most widely used in the field of treatment of illicit drugs, as they reflect biological verification of recent use. Other sources of biological data (e.g., hair, nails, skin, saliva) were not included here because they are not yet commonly used in clinical trials (Donovan et al., 2012) and were not collected in the studies included in this report. 3 Longest period of consecutive abstinence during treatment. "
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    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.
    Drug and alcohol dependence 04/2014; 137(1). DOI:10.1016/j.drugalcdep.2014.01.012 · 3.42 Impact Factor
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