Generalizability of findings from randomized controlled trials: application to the National Institute of Drug Abuse Clinical Trials Network

Aims: To compare randomized controlled trial (RCT) sample treatment effects with the population effects of substance use disorder (SUD) treatment. Design: Statistical weighting was used to re-compute the effects from 10 RCTs such that the participants in the trials had characteristics that resembled those of patients in the target populations. Settings: Multi-site RCTs and usual SUD treatment settings in the United States. Participants: A total of 3592 patients in 10 RCTs and 1 602 226 patients from usual SUD treatment settings between 2001 and 2009. Measurements: Three outcomes of SUD treatment were examined: retention, urine toxicology and abstinence. We weighted the RCT sample treatment effects using propensity scores representing the conditional probability of participating in RCTs. Findings: Weighting the samples changed the significance of estimated sample treatment effects. Most commonly, positive effects of trials became statistically non-significant after weighting (three trials for retention and urine toxicology and one trial for abstinence); also, non-significant effects became significantly positive (one trial for abstinence) and significantly negative effects became non-significant (two trials for abstinence). There was suggestive evidence of treatment effect heterogeneity in subgroups that are under- or over-represented in the trials, some of which were consistent with the differences in average treatment effects between weighted and unweighted results. Conclusions: The findings of randomized controlled trials (RCTs) for substance use disorder treatment do not appear to be directly generalizable to target populations when the RCT samples do not reflect adequately the target populations and there is treatment effect heterogeneity across patient subgroups.