Limitations
This study has several limitations. One limitation to these data are that outcomes were highly influenced by missing data, which was not unexpected given the extended (30-week) monitoring period and thrice-weekly visit schedule. Missingness within the RP MITT subgroup contributed to a visible advantage of placebo compared with bupropion SR in missing-positive analyses, although missing data in this group appeared to be unrelated to study medication or procedures. In persons assigned to AI, overall rates of urine sample submission declined at a similar rate within both medication groups during the 7 to 26–week incentive intervention period. The positive signal for bupropion SR among participants in the AI group was not significant in the MITT sample but was statistically-significant in the completer subsample. Although the completer sample had less variability and missing data than the MITT sample, it was also a self-selected sample that was therefore subject to bias, which complicates interpretation. The lack of data on concurrent opioid use by study participants and changes in methadone medication treatment is a limitation of this study. Additionally, several between-group comparisons may not have reached statistical significance owing to lack of power but may still represent clinically meaningful differences.