The Paradox of the Placebo
While the proposal by Fergusson et al (1), regarding post hoc
assessment of the success of blinding in RCTs, is problematic, it does
suggest an intriguing dimension of the so-called placebo effect. If the
intervention being studied in the RCT is truly more efficacious than
placebo, then, as noted in several of the response letters (2,3,4),
blinding can be invalidated through patients correctly guessing their
allocation by gauging their individual responses to treatment (leaving
aside the issue of side effects). In such a scenario, improvement due to
the treatment intervention is perhaps compounded by further improvement
brought on through the expectation of improvement, once blinding has been
This effect might be most pertinent in trials of depression drugs,
where continuous subjectively-assessed outcomes are typically used and
where placebo effects may therefore occur (5). A patient randomized to
receive the drug begins to feel better, correctly guesses his or her
allocation, then possibly benefits further from the very expectation of
improvement. In short, the positive effects of expectation might be more
pronounced in the treatment group and less pronounced in the placebo
The individual assessing outcomes might be similarly affected, since
he or she might also correctly guess the patient's allocation. In studies
with serial assessments, future assessments could then be biased.
For treatments that show dramatic results, RCTs may overestimate the
actual size of the treatment effect relative to placebo. It may then be
more appropriate to speak of testing the whole treatment experience,
rather than purporting to test the specific effectiveness of the
1. Fergusson D, Glass KC, Waring D, Shapiro S. Turning a blind eye:
the success of blinding reported in a random sample of randomised, placebo
controlled trials. BMJ 2004; 328:432.
2. Altman DG, Schulz KF, Moher D. Turning a blind eye: testing the
success of blinding and the CONSORT statement. BMJ. 2004;328:1135.
3. Senn SJ. Turning a blind eye: authors have blinkered view of
blinding. BMJ. 2004; 328:1135-6.
4. Sackett DL.Turning a blind eye: why we don't test for blindness at
the end of our trials. BMJ. 2004; 328:1136.
5. Hrobjartsson A, Gotzsche PC. Is the placebo powerless? An analysis
of clinical trials comparing placebo with no treatment. N Engl J Med 2001;
Competing interests: No competing interests