1. Machine Learning-Driven Analysis of Individualized Treatment Effects Comparing Buprenorphine and Naltrexone in Opioid Use Disorder Relapse Prevention.
- Author
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Afshar M, Graham Linck EJ, Spicer AB, Rotrosen J, Salisbury-Afshar EM, Sinha P, Semler MW, and Churpek MM
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Buprenorphine therapeutic use, Buprenorphine administration & dosage, Delayed-Action Preparations, Precision Medicine, Opiate Substitution Treatment methods, Opioid-Related Disorders drug therapy, Machine Learning, Narcotic Antagonists therapeutic use, Narcotic Antagonists administration & dosage, Naltrexone therapeutic use, Naltrexone administration & dosage, Secondary Prevention methods, Buprenorphine, Naloxone Drug Combination therapeutic use
- Abstract
Objective: A trial comparing extended-release naltrexone and sublingual buprenorphine-naloxone demonstrated higher relapse rates in individuals randomized to extended-release naltrexone. The effectiveness of treatment might vary based on patient characteristics. We hypothesized that causal machine learning would identify individualized treatment effects for each medication., Methods: This is a secondary analysis of a multicenter randomized trial that compared the effectiveness of extended-release naltrexone versus buprenorphine-naloxone for preventing relapse of opioid misuse. Three machine learning models were derived using all trial participants with 50% randomly selected for training (n = 285) and the remaining 50% for validation. Individualized treatment effect was measured by the Qini value and c-for-benefit, with the absence of relapse denoting treatment success. Patients were grouped into quartiles by predicted individualized treatment effect to examine differences in characteristics and the observed treatment effects., Results: The best-performing model had a Qini value of 4.45 (95% confidence interval, 1.02-7.83) and a c-for-benefit of 0.63 (95% confidence interval, 0.53-0.68). The quartile most likely to benefit from buprenorphine-naloxone had a 35% absolute benefit from this treatment, and at study entry, they had a high median opioid withdrawal score ( P < 0.001), used cocaine on more days over the prior 30 days than other quartiles ( P < 0.001), and had highest proportions with alcohol and cocaine use disorder ( P ≤ 0.02). Quartile 4 individuals were predicted to be most likely to benefit from extended-release naltrexone, with the greatest proportion having heroin drug preference ( P = 0.02) and all experiencing homelessness ( P < 0.001)., Conclusions: Causal machine learning identified differing individualized treatment effects between medications based on characteristics associated with preventing relapse., Competing Interests: Conflicts of Interest: None., (Copyright © 2024 American Society of Addiction Medicine.)
- Published
- 2024
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