Drug Class Review: Long-Acting Opioid Analgesics: Final Update 6 Report [Internet]

Purpose: We compared the effectiveness and harms of long-acting opioids and of long-acting opioids compared with short-acting opioids in adults with chronic noncancer pain.

Data Sources: To identify published studies, we searched MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and reference lists of included studies. We also searched the US Food and Drug Administration Center for Drug Evaluation and Research website for additional unpublished data and solicited dossiers of information from pharmaceutical manufacturers.

Review Methods: Study selection, data abstraction, validity assessment, grading the strength of the evidence, and data synthesis were all carried out according to standard Drug Effectiveness Review Project review methods.

Results and Conclusions: Although we identified 10 head-to-head trials comparing 2 or more long-acting opioids, the evidence was insufficient to determine if there are differences among long-acting opioids in effectiveness or harms. Eight trials found no statistical difference in pain relief or function between long-acting opioids. The 2 trials which found a significant difference were both open-label, rated poor quality, and were inconsistent with higher-quality trials evaluating the same comparison that found no significant differences. A shortcoming of the currently available evidence is that comparisons between specific long-acting opioids have been evaluated in only 1 to 3 trials each (most with small sample sizes), which may limit statistical power for detecting true differences. Studies that provided indirect data were too heterogeneous in terms of study design, patient populations, interventions, assessed outcomes, and results to make accurate judgments regarding comparative efficacy or adverse event rates. Evidence was insufficient to determine if long-acting opioids as a class are more effective or associated with fewer harms than short-acting opioids. There was also insufficient evidence to draw conclusions about comparative effectiveness or safety in subgroups.