Evaluating IMMPACT Criteria for the Clinical Meaningfulness of Between-Group Differences: Interpreting Randomized Trial Results within a Context of Existing Chronic Pain Analgesics.

Abstract

The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has published methods and consensus benchmarks for determining the clinical meaningfulness of analgesic clinical trial results. However, results are commonly misinterpreted when within-subject thresholds for clinical meaningfulness are applied to between-group differences (ie, active vs placebo). IMMPACT has emphasized that between-group differences must be interpreted on a case-by-case basis and previously published a qualitative framework that is informed by quantitative analyses, drawing on data from within an individual study together with external sources. We tested this framework by applying it to a recently completed Phase 3 clinical study (the CLEAR Trial), which assessed the efficacy and safety of SP-102-a viscous dexamethasone product for transforaminal (TF) epidural administration-versus placebo for the treatment of lumbosacral radicular pain (LRP). To contextualize the efficacy results, we conducted a narrative review and comparative analysis of all FDA-approved pharmaceutical products for chronic pain conditions and of off-label TF steroid injection studies. This article presents conclusions regarding both the utility of the IMMPACT framework and the clinical meaningfulness of the results of the example trial. Implementing the framework was generally straightforward, although it required user discretion in several areas and exposed several limitations within both the framework itself and the underlying clinical study data. Based on the IMMPACT framework, SP-102 appears to provide a clinically meaningful benefit in between-group comparisons.