Responsiveness of Single versus Composite Measures of Pain in Knee Osteoarthritis

Objective In rheumatoid arthritis, composite outcomes constructed from a combination of outcome measures are widely used to enhance responsiveness (sensitivity to change) and comprehensively summarize response. WOMAC pain is the primary outcome measure in many osteoarthritis (OA) trials. Information from other outcomes, such as rescue medication use, and other WOMAC subscales, could be added to create composite outcomes, but the sensitivity of such a composite has not been tested. Method We used data from a completed trial of Tanezumab for knee OA (NCT00733902). The WOMAC questionnaire and rescue medication use were measured at multiple time points, up to 16 weeks. Pain and rescue medication outcomes were standardised and combined into 3 composite outcomes via principal components analysis to produce one score (composite outcome) and their responsiveness was compared to WOMAC pain, the standard. We pooled all treatment doses of Tanezumab into one ‘treatment’ group, for simplicity, and compared this to the control group (placebo). Results The composite outcomes showed modestly but not statistically significantly greater responsiveness when compared to WOMAC pain alone. Adding information on rescue medication to the composite improved responsiveness. While improvements in sensitivity were modest, the required sample sizes for trials using composites was 20- 40% less than trials using WOMAC pain alone Page 4 of 55 Page 4 of 23 Conclusion Combining information from related, but distinct, outcomes considered relevant to a particular treatment improved responsiveness, could reduce sample size requirements in OA trials and might offer a way to better detect treatment efficacy in OA trials