David Doggett writes:
>This raises a point that has always puzzled me. RCTs are
>only considered ethical if there is equipoise. But what can the
>evidence be for equipoise? EBM only recognizes RCTs as valid
>evidence. As far as I know, EBM is silent on what the evidence
>must be for equipoise. Any thoughts anyone?
I addressed this topic (indirectly) in an email to the Evidence-Based-Health
group and Jeanne Lenzer. I am working on this issue on a web page:
that discusses the ethics of placebo controlled trials. As in the other
email, I want to encourage any of the readers of this group to provide me
feedback. The page is still an early draft.
In the other email, I talked about lung reduction surgery for patients with
severe emphysema. Many doctors embraced a 1996 study that compared 150
consecutive surgeries to a historical control group. They apparently felt
that this non-randomized study was sufficient to upset equipoise in favor of
the surgery, although a randomized trial has shown that the opposite was
true, at least for some patients.
Weijer, Shapiro, and Glass (2000) have argued that information "on personal
experience, on anecdote, on tacit understanding, or rules of thumb" is
sufficient to upset equipoise but that a "hunch" is not sufficient.
That same article highlights the debate between the uncertainty principle
(which I would call individual equipoise) and community equipoise. An
interesting argument would be that equipoise exists until a randomized study
has been done. I have not heard anyone make that argument directly, but is
appears to be implied by some arguments in favor of community equipoise.
Others have argued (see some of the arguments in William Silverman's book)
that you need to randomize from the very first patient, before there is a
chance for non-randomized data to upset equipoise. This strikes me as a bit
naive. Some therapies require a bit of preliminary data before they can even
be considered equivalent to placebo, because they have serious side effects.
Furthermore, some therapies like surgery require some training and
experience before they can be incorporated into the context of a clinical
trial. Besides, if equipoise is such a fragile thing that a few preliminary
non-randomized patients can upset it, then why wouldn't promising results in
an animal model also upset equipoise?
The issue is further clouded when a regulatory agency, such as the United
States Food and Drug Administration, requires a strong level of evidence
(typically two randomized trials) before a new drug is approved. Wouldn't
equipoise be violated in the replication study (the second study)?
And Stephen Senn has argued in an eLetter to the BMJ that equipoise is not
required for an ethical trial.
Placebo confusion Stephen Senn, BMJ eletters. 15 August 2000
Where's the Evidence? : Debates in Modern Medicine by William A. Silverman
(1999) Oxford Univ Press; ISBN: 0192630881.
For and against: Clinical equipoise and not the uncertainty principle is the
moral underpinning of the randomised controlled trial * FOR * AGAINST
Charles Weijer, Stanley H Shapiro, Kathleen Cranley Glass, and Murray W
Enkin. BMJ 2000; 321: 756-758.
You can get the full text of this article from the bmj.com web site.
Steve Simon, [log in to unmask], Standard Disclaimer.
STATS: STeve's Attempt to Teach Statistics. http://www.cmh.edu/stats
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