Covariate Adjustment in Chronic Pain Trials: An Oft-Missed Opportunity.

Self-reported pain intensity, frequently used as an outcome in randomized clinical trials (RCTs) of chronic pain, is often highly variable and could be associated with multiple baseline factors. Thus, the assay sensitivity of pain trials (ie, the ability of the trial to detect a true treatment effect) could be improved by including prespecified baseline factors in the primary statistical model. The objective of this focus article was to characterize the baseline factors included in statistical analyses of chronic pain RCTs. Seventy-three RCTs published between 2016 and 2021 that investigated interventions for chronic pain were included. The majority of trials identified a single primary analysis (72.6%; n = 53). Of these, 60.4% (n = 32) included one or more covariates in the primary statistical model, most commonly baseline value of the primary outcome, study site, sex, and age. Only one of the trials reported information regarding associations between covariates and outcomes (ie, information that could inform prioritization of covariates for prespecification in future analyses). These findings demonstrate inconsistent use of covariates in the statistical models in chronic pain clinical trials. Prespecified adjustments for baseline covariates that could increase precision and assay sensitivity should be considered in future clinical trials of chronic pain treatments. PERSPECTIVE: This review demonstrates inconsistent inclusion and potential underutilization of covariate adjustment in analyses of chronic pain RCTs. This article highlights areas for possible improvement in design and reporting related to covariate adjustment to improve efficiency in future RCTs.

Evaluating predictors of pain reduction after genicular nerve radiofrequency ablation for chronic knee pain.

Aim: Radiofrequency ablation (RFA) of genicular nerves can treat refractory chronic knee pain. This study evaluated association between patient and procedural characteristics and pain improvement after genicular nerve RFA. Materials & methods: A retrospective chart review. Data were extracted from patients who underwent thermal or cooled RFA of the knee. Results: A total of 124 patients were included. 81% of patients reported ≥75% pain relief after diagnostic nerve blocks. 35% reported ≥50% pain reduction from the RFA. Predictors of improved pain outcomes included higher baseline pain, no depression and thermal (vs cooled) RFA. Conclusion: Identifying patients who may benefit the most from genicular RFA is still not clear. Pain reduction differences between patients with and without depression and RFA type deserves further exploration.

Lay abstract Aim: Using heat energy to stun the nerves (Radiofrequency ablation) that supply knee joint is a technique that can be used to decrease persistent knee pain. This study was performed to try to see if there are any ways that doctors are able to predict which patients will benefit from this therapy. Materials & methods: The data were collected by reviewing charts. Results: A total of 124 patients were included in this study. The data did not show that good pain relief after diagnostic injection guaranteed success with this technique of stunning of the nerve with heat energy (RFA). The things that can possibly predict success are more severe pain to start with, people who do not suffer from depression and use of higher level of heat energy to stun the nerves. Conclusion: It is still not clear which patients will benefit from this technique of stunning the nerves of the knee with heat energy.