How much of the placebo ‘effect’ is really statistical regression?

Abstract

Statistical regression to the mean predicts that patients selected for abnormalcy will, on the average, tend to improve. We argue that most improvements attributed to the placebo effect are actually instances of statistical regression. First, whereas older clinical trials susceptible to regression resulted in a marked improvement in placebo‐treated patients, in a modern series of clinical trials whose design tended to protect against regression, we found no significant improvement (median change 0·3 per cent, p > 0·05) in placebo‐treated patients. Secondly, regression can yield sizeable improvements, even among biochemical tests. Among a series of 15 biochemical tests, theoretical estimates of the improvement due to regression by selection of patients as high abnormals (i.e. 3 standard deviations above the mean) ranged from 2·5 per cent for serum sodium to 26 per cent for serum lactate dehydrogenase (median 10 per cent); empirical estimates ranged from 3·8 per cent for serum chloride to 37·3 per cent for serum phosphorus (median 9·5 per cent). Thus, we urge caution in interpreting patient improvements as causal effects of our actions and should avoid the conceit of assuming that our personal presence has strong healing powers.