Intended for healthcare professionals

Rapid response to:

Education And Debate

For and againstDeclaration of Helsinki should be strengthenedForAGAINSTRothman and Michels' riposte

BMJ 2000; 321 doi: https://doi.org/10.1136/bmj.321.7258.442 (Published 12 August 2000) Cite this as: BMJ 2000;321:442

Rapid Response:

Placebo confusion

The paper by Rothman and Michels1 will only serve to confuse the
issues. A placebo is always specific to a given treatment. Its purpose is
to blind that treatment, since for any other purpose it would be
sufficient simply to have a control group in which the experimental
treatment was withheld. The issue as to whether a placebo is given is
logically independent of the decision as to whether a standard "effective"
treatment is withheld. Placebo-controlled trials are frequently run as
"add-on" trials. Indeed, when we consider that the list of effective
treatments for all diseases includes, food, water, air and nursing care,
all trials are (or should be!) add-on trials. The pure "no-treatment"
group is a myth. The question is, how much of standard care to maintain
when running a placebo controlled trial: frequently the answer has to be
"all".

In running a trial, the ethical issue is whether it is acceptable to
withhold a standard available effective treatment. In the context of drug
development, the experimental treatment is not generally available.
Society has mandated the regulator to withhold treatments, until proved
efficacious, except under the special circumstances of a clinical trial.
This can be justified in terms of John Rawls's Theory of Justice2 as being
a choice we would make in "the original position" regarding the sort of
society we want to live in.

Equipoise is an irrelevance3. Patients are entered onto the trial
because the trialists believe that the experimental treatment is better.
The control group treatment should be as good as that available outside
the trial. Experimentation continues until either the trialists are
convinced they are wrong (equipoise is reached) or they convince Society
they are right.

This is not to say that placebos are not sometimes used in ways in
drug development that are unethical. One such use is in placebo run-
ins3,4. These violate consent and should be abandoned.

Declaration of interest: the author is a consultant to the
pharmaceutical industry

References

1 Rothman KJ, Michels, KB. Declaration of Helsinki should be
strengthened: for. BMJ 2000;321:442-5

2 Rawls, JA Theory of Justice. Oxford: Oxford University Press, 1972

3 Senn SJ. Statistical Issues in Drug Development. Chichester: Wiley,
1997.

4 Senn SJ. (1997) Are placebo run ins justified? BMJ 2000; 314:
1191-3.

Competing interests: No competing interests

15 August 2000
Stephen Senn
Professor of Pharmaceutical and Heath Statistics
UCL (University College London)