Journal of Addiction Medicine 2022;16(4):440-446. [doi: 10.1097/ADM.0000000000000931]
Ajazi, Elizabeth M. | Dasgupta, Nabarun | Marshall, Stephen W. | Monaco, Jane | Howard, Annie Green | Preisser, John S. | Schwartz, Todd A.
This paper illustrates survival models for analysis of trials of substance use treatment programs. It uses public release data from a study of extended-release naltrexone (XR-NTX), relative to buprenorphine-naloxone (BUP-NX), the CTN-0051 (X:BOT) study. X:BOT compared XR-NTX to BUP-NX on 2 efficacy outcomes (opioid relapse, use of nonprescribed opioids; positive opioid urine test) and 1 safety outcome (overdose). Intention-to-treat (ITT) and per-protocol approaches were implemented using surviving models that included treatment-by-time interactions.
Consistent with original trial findings, 72% of XR-NTX and 94% of BUP-NX subjects initiated treatment: the ITT hazard ratio for XR-NTX relative to BUP-NX was 1.4 for opioid relapse and 1.31 for positive urine test. Using treatment-by-time interactions, researchers examined the time-dependent effect of XR-NTX and found an elevated ITT overdose hazard ratio of 2.4 overall and 3.8 during the study treatment phase. This result (28 overdoses overall; 17 during the study treatment phase) contrasts with previous analysis, which reported minimal differences in overdose between XR-NTX and BUP-NX.
Conclusions: An advantage of using time-dependent Cox models is its ability to isolate effects during specific periods. In general, our survival analyses concur with the conclusions of Lee et al (2018) for the efficacy outcomes, which demonstrated supriority of BUP-NX. In contrast to the original report, this analysis indicates a greater risk of overdose for XR-NTX, dominantly during the study treatment phase. Further investigation of this finding is a pressing research priority.
Keywords: CTN platform/ancillary study | Buprenorphine/Naloxone | Naltrexone | Opioid use disorder | Pharmacological therapy | Overdose | Journal of Addiction Medicine (journal)
Document No: 1504 ; PMID: 35960214
Submitted by: CTN Dissemination Librarian (3/16/2022)
