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.
    No preview · Article · Oct 2015 · Drug and alcohol dependence
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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.
    Full-text · Article · Apr 2014 · Drug and alcohol dependence
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    • "First, the accuracy of self-reported substance use is frequently questioned due to substantial underreporting. However, in our study, cannabis use was elicited by experienced investigators and underreporting minimized through assurances of confidentiality, lack of adverse consequences, appropriate recall cues, and other confirmatory biological markers for confirmation (46). Even if underreported, cannabis use was significant in our study. "
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    ABSTRACT: OBJECTIVE We examined if chronic cannabis smoking is associated with hepatic steatosis, insulin resistance, reduced β-cell function, or dyslipidemia in healthy individuals.RESEARCH DESIGN AND METHODS In a cross-sectional, case-control study, we studied cannabis smokers (n = 30; women, 12; men, 18; 27 ± 8 years) and control subjects (n = 30) matched for age, sex, ethnicity, and BMI (27 ± 6). Abdominal fat depots and intrahepatic fat content were quantified by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Insulin-sensitivity indices and various aspects of β-cell function were derived from oral glucose tolerance tests (OGTT).RESULTSSelf-reported cannabis use was: 9.5 (2-38) years; joints/day: 6 (3-30) [median (range)]. Carbohydrate intake and percent calories from carbohydrates, but not total energy intake, were significantly higher in cannabis smokers. There were no group differences in percent total body fat, or hepatic fat, but cannabis smokers had a higher percent abdominal visceral fat (18 ± 9 vs. 12 ± 5%; P = 0.004). Cannabis smokers had lower plasma HDL cholesterol (49 ± 14 vs. 55 ± 13 mg/dL; P = 0.02), but fasting levels of glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, or free fatty acids (FFA) were not different. Adipocyte insulin resistance index and percent FFA suppression during an OGTT was lower (P < 0.05) in cannabis smokers. However, oral glucose insulin sensitivity index, measures of β-cell function, or incretin concentrations did not differ between the groups.CONCLUSIONS Chronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic β-cell function, or glucose intolerance.
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