Cautionary tales in the clinical interpretation of trials assessing therapy-induced changes in health status

Trials assessing the effects of therapies on symptoms, functional capacity, health-related quality of life and other aspects of health status are becoming more common in an era of chronic disease management. Such trials involve instruments for measuring health status whose reliability, validity and responsiveness need to be understood by clinicians and policy-makers in interpreting trial results. Deciding whether a treatment is clinically efficacious requires prior determination, based on empirical evidence, of what constitutes a minimal important difference (MID) between active treatment and control groups in the change in health status between study start and end. This MID should be used to calculate the sample size that will confer adequate power to detect a treatment effect if it truly exists. Many trials assessing health status have major methodological flaws: use of inappropriate or psychometrically unsound measurement instruments, lack of specification of MID, assumption that statistically significant results represent clinically significant treatment effects, and statement of conclusions inconsistent with observed results. This article provides guidance to clinicians in interpreting results of such trials in regard to clinical decision-making.