H. Mcquay et al., VARIATION IN THE PLACEBO-EFFECT IN RANDOMIZED CONTROLLED TRIALS OF ANALGESICS - ALL IS AS BLIND AS IT SEEMS, Pain, 64(2), 1996, pp. 331-335
The objective was to investigate the relationship between pain relief
scores produced by placebo and by active interventions in randomised c
ontrolled trials (RCTs). Individual patient categorical pain relief sc
ores from 5 placebo-controlled single-dose parallel-group RCTs in acut
e postoperative pain were used to calculate the percentage of the maxi
mum possible pain relief score (%maxTOTPAR) for the different treatmen
ts. One hundred and thirty of the 525 patients in the 5 trials had a p
lacebo. 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 r
elief 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 c
onsiderably 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 pl
acebo scores should not vary. Despite these conditions being met the p
lacebo scores did vary. The previous explanation, of a relationship be
tween the mean placebo scores and the mean scores for the active treat
ments was not supported.