Methods used to Account for Concurrent Analgesic Use in Randomized Controlled Trials of Interventional Pain Treatments: A Meta-Epidemiologic Study

ObjectiveThe modest effect sizes of most pain treatments make it essential that randomized controlled trials (RCTs) use methods that clearly define treatment effects of interest and consider the role of concurrent treatments. This study aims to determine how frequently concurrent analgesic use is reported in interventional pain RCTs and how accounting for analgesic use can affect pain intensity outcomes. DesignMeta-epidemiologic study. MethodsWe conducted a study of concurrent analgesic use among RCTs from a recent systematic review of non-surgical interventional pain treatments (n= 37). We calculated the prevalence of different methods used to report concurrent analgesic use. We performed meta-analyses to compare treatment effects on pain intensity with vs. without accounting for concurrent analgesic use via a novel quantitative composite outcome, the "QPAC1.5." ResultsAbout half of interventional pain RCTs reported concurrent analgesic use, but only one RCT directly accounted for concurrent analgesic use in their pain intensity outcome. Analyses accounting for concurrent analgesic use using the QPAC1.5 substantially increased the estimated treatment effect of interventions on pain intensity by an average of -0.45 numeric rating scale points (95% CI -0.76 to -0.14; p<0.001), as compared to analyses that did not adjust for analgesic use. ConclusionConcurrent analgesic use is sometimes reported in interventional pain RCTs, but rarely accounted for when examining treatment effects on pain intensity. Accounting for concurrent analgesic use changes the treatment effect of interest to remove differential analgesic rates and has the potential to significantly affect estimates of effect sizes on pain treatments.