III. Detecting Treatment Effects in Clinical Trials With Different Indices of Pain Intensity Derived From Ecological...

Pain intensity represents the primary outcome in most pain clinical trials. Identifying methods to measure aspects of pain that are most sensitive to treatment may facilitate discovery of effective interventions. In this third of 3 articles examining alternative indices of pain intensity derived from ecological momentary assessments (EMA), we compare treatment effects based on Average Pain, Maximum Pain, Minimum Pain, Pain Variability, Time in High Pain, Time in Low Pain, and Pain After Wake-Up. We also examine which indices contribute to Patient Global Impressions of Change (PGIC). Data came from 2 randomized, double-blind, placebo-controlled trials examining the efficacy of milnacipran for fibromyalgia treatment; 2,084 patients provided >1 million EMA pain intensity ratings over 24 (Study 1) or 26 (Study 2) treatment weeks. Pain Variability and Time in High Pain produced significantly smaller treatment effects than Average Pain; other pain indices showed effects that were numerically smaller, but not significantly different from Average Pain. Changes in all pain indices were significantly associated with PGIC, with improvements in Maximum Pain and in Pain Variability offering small incremental contributions to understanding PGIC over Average Pain. Results suggest that different pain indices could be used to detect treatment effects in pain clinical trials. PERSPECTIVE: Alternative summary measures of pain intensity derived from EMA may broaden the scope of outcomes useful in pain clinical trials. In this analysis of a pharmacological treatment for fibromyalgia, most pain summary measures indicated similar effects; improvements in Maximum Pain and Pain Variability contributed to understanding PGIC over Average Pain.