This paper describes Project Harmony, a Virtual Clinical Trial (VCT) funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) to harmonize and analyze data from over 40 independent psychological, pharmacologic and/or combined pharmacological treatment studies for posttraumatic stress disorder and comorbid alcohol and other drug use disorders (PTSD/AOD). The study attends to three distinct analysis challenges: (1) variation in measurement of PTSD/AOD across studies, time, populations and reporters, (2) cross-study variation in treatment effect sizes and (3) non-randomized, cross-study variation in the classification of treatments (despite within-study randomization of treatment arms). To address these challenges, the study combines meta-analysis of individual patient data (MIPD), integrative data analysis (IDA) and propensity score weighting (PSW) to integrate raw data from these clinical trials. This protocol shows how this VCT analytic framework was used to (1) develop commensurate scale scores of PTSD and AOD severity when measures vary across studies, (2) compare the efficacy of evidence-based treatment models for PTSD/AOD, (3) test for potential mediators of treatment effects on AOD and PTSD across treatment models, and (4) explore individual- and study-level moderators to inform for whom each of the treatment models works best. The advantages of the general VCT approach are juxtaposed against the limitations of single randomized controlled trials and conventional meta-analysis.
Keywords: Alcohol; Meta analysis of individual patient data; PTSD; Propensity score weighting; Substance use disorders; Virtual clinical trial.
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