Stratification of flare intensity identifies placebo responders in a treatment efficacy trial of patients with osteoarthritis

Objective. Studies evaluating osteoarthritis treatment often use increased arthritis activity ("flare") as a selection criterion, although no standard ized assessments are available to quantify flare intensity and little is kn own about how this criterion affects treatment comparisons. This study eval uated the reliability of a flare assessment and how pretreatment flare inte nsity impacts conclusions on treatment efficacy. Methods. Using data from a double-blind, randomized, controlled trial (n = 182), we compared 3 osteoarthritis treatments with placebo in patients who met 3 of 4 flare criteria. The Western Ontario and McMaster Universities Os teoarthritis Index (WOMAC) questionnaire was used to document levels of pai n, stiffness, and physical functioning at baseline an at the final visit. F ollowing factor analytic evaluation, the flare items were standardized and summed to create a flare intensity index, which was used to identify patien t subgroups. Analysis of covariance was applied to compare change in WOMAC scale scores from baseline to final visit for assessment of treatment diffe rences among the flare intensity subgroups. Results. The flare indicators appeared unidimensional. Analyses were strati fied by tertiles of flare intensity. Mean WOMAC scores improved in the pati ents receiving active treatment who were categorized into the 2 lowest flar e intensity subgroups, but mean WOMAC scores improved in patients in all 4 treatment groups (active and placebo) in the most intense flare subgroup. Conclusion. Patients with higher intensity flares may be more likely to rep ort substantial improvement in functional status regardless of treatment. F ailure to account for flare intensity in analyses of data from pain trials with flare-based designs may inflate the risk of Type I and Type II errors in the interpretation of study results.