Variation in the placebo effect in randomised controlled trials of analgesics: all is as blind as it seems.

The objective was to investigate the relationship between pain relief scores produced by placebo and by active interventions in randomised controlled trials (RCTs). Individual patient categorical pain relief scores from 5 placebo-controlled single-dose parallel-group RCTs in acute postoperative pain were used to calculate the percentage of the maximum possible pain relief score (%maxTOTPAR) for the different treatments. One hundred and thirty of the 525 patients in the 5 trials had a placebo. Individual patients' scores with placebo varied from 0 to 100% of the maximum possible pain relief. The proportion who obtained more than 50% of the maximum possible pain relief with placebo varied from 7% to 37% across the trials; with the active drugs the variation was from 5 to 63%. Mean placebo scores were related to the mean score for the active treatments in each study; the higher the mean active score, the higher the mean placebo score. This relationship disappeared when median values were used. Medical folklore has it that the amount of relief obtained with placebo is one-third of the maximum possible (and does not vary), and that one-third of patients respond to placebo. The results show that the amount of relief obtained with placebo varies considerably between patients, that 38% of patients obtained more than 10% of the maximum possible relief, and 16% obtained greater than 50%. In double-blind, randomised parallel-group studies of high quality placebo scores should not vary. Despite these conditions being met the placebo scores did vary. The previous explanation, of a relationship between the mean placebo scores and the mean scores for the active treatments was not supported.