"The X:BOT study is an influential randomised trial comparing safety and efficacy of buprenorphine and naltrexone to treat opioid dependence.1 The original publication reported no statistically significant difference in the safety endpoint of overdose.1 We reanalysed the trial using the public dataset2 and replicated most findings.3, 4 However, we identified six additional overdose events that the original analysis missed. Five of these additional events were in the naltrexone group, and one was in the buprenorphine group.
"Assuming similar efficacy, inclusion of these originally misclassified cases fundamentally alters the clinical risk–benefit: 19 (7%) of 283 participants had overdoses in the naltrexone group compared with 9 (3%) of 287 in the buprenorphine group (appendix).3 In addition to correcting the misclassification, our reanalysis3 accounted for timing of safety outcomes. The hazard ratio (HR) for overdose in the naltrexone group, relative to buprenorphine, becomes 2·40 (95% CI 1·09–5·30, p=0·03; appendix) with misclassification corrected. After we published our reanalysis,3 the presence of additional overdoses was confirmed by the original authors.5"
Dasgupta N, Ajazi EM, Schwartz TA, Marshall SW. Misclassification of overdose events in the X:BOT study. Lancet. 2023;402(10401):526-527. doi:10.1016/S0140-6736(23)00113-7
