Scoping Review of Off-Label Topical Analgesia in Palliative, Hospice and Cancer Care: Towards Flexibility in Evidence-Based Medicine

Purpose: Scoping reviews address the nature of the literature per se rather than inferring evidence-based treatment guidelines. Scoping reviews of the published literature are intended to describe the aggregated nature of the evidence surrounding some agent or intervention, in contrast to systematic reviews that seek when possible to guide clinical practice. We conducted a scoping review to identify reports of potential clinical utility of off-label topical analgesics and adjuvants when FDA-approved treatments have proven inadequate. Methods: We performed a comprehensive search of three databases (PubMed, Web of Science and Embase) for articles dating from 1947 to the present. Mindful that FDA approved and WHO-recommended analgesic medications often prove inadequate for individual patients in extremis with palliative, hospice or cancer pain, we used broad, structured inclusion criteria to retrieve articles. Results: We retrieved 12,100 articles; after screening, we had 39 reports addressing 19 different topical agents out of the 32 chemical entities. Our scoping review disclosed evidence about agents that might not have met inclusion criteria for clinical practice guidelines. Discussion: Although generally considered lower quality evidence, case reports or series present suggestions for diverse topical medications to manage pain in challenging circumstances when high-quality evidence for agents and routes of administration is lacking. Conclusion: Patients with the greatest need for evidence to identify and guide lesser-used agents during aggressive pain management are the most difficult to enroll and follow in standardized, controlled and/or blinded clinical trials. This scoping review identifies medications, dosages, and routes of topical agents reported to be effective in these often-challenging circumstances. Until larger and higher quality studies are completed, we must rely on the best available evidence even if of lower quality.