Treatment development and evaluation for substance use disorders are hindered when randomized controlled trials fail to show a treatment effect when one exists. This manuscript provides an overview of addressable methodological factors that may contribute to incorrect trial results. The collection of remote, naturalistic, real-time adherence and substance use data through ambulatory assessment methods in everyday life is presented as a partial solution. Other recommendations related to participant recruitment and selection, ensuring adequate consistency/fidelity and dose of treatment, and rigorously assessing clinical outcomes are discussed. With implementation of eligibility criteria verification, treatment adherence monitoring, and remote assessment of substance use and biomarkers, ambulatory assessment may help improve clinical trial success rates by improving precision, increasing reproducibility, and reducing the impact of methodological issues that may lead to inaccurate trial results.
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