dr simon's interpretation of the uncertainty principle is not the one
that's held here in oxford at the clinical trials service unit where
richard peto works.
the problem being addressed here is not adherence to entry criteria but
the thorny issue we clinicians and researchers face when grappling with
the ethics of human experimentation.
briefly, it suggests that whether a specific patient who already fits the
entry criteria for a trial ought to be entered into the trial depends (in
addition to other key elements such as informed consent) on the state of
certainty/uncetainty in the mind of the admitting clinician about whether
the intervention under study would be helpful or harmful.
if the clinician is convinced that the intervention would benefit this
particualr patient, the patient is not randomised, but is offered the
intervention outside the trial.
if the clinician is convinced that the intervention would harm this
particular patient, the patient is not randomised, but is informed and
advised against the intervention.
it is when the clinician is uncertain whether the patient would benefit
from the intervention that informed consent is requested and the patient
is randomised.
as a clinician-trialist involved one way or another in about 200 trials,
it's my experience that the uncertainty principle makes it far easier on
both sides of the protocol (we avoid the perplexing and [for most of us,
incorrect] arguments about the need for "equilibrium", on the one hand,
but are free to exercise clinical judgement when we're certain a patient
will benefit/ be harmed from the treatment under study).
(the randomisation process often involves "minimisation" for balance as
well)
i hope that this clarifies the discussion.
cheers
dls
............................................................................
Prof David L. Sackett
Director, NHS R&D Centre for Evidence-Based Medicine
Consultant in Medicine Editor, Evidence-Based Medicine
Nuffield Department of Medicine, University of Oxford
Level 5, John Radcliffe Hospital, Oxford OX3 9DU, England
Phone: +44-(0)1865-221320 Fax: +44-(0)1865 222901
Email: [log in to unmask] WWW: http://cebm.jr2.ox.ac.uk
............................................................................
On Mon, 14 Dec 1998, Simon, Steve, PhD wrote:
> Ronald Ingle writes:
>
> >In BMJ 1998;317:1170 (31 October) Richard Peto writes that
> >using "the uncertainty principle" simplifies entry criteria
> >in randomised trials.
> >
> >I understand the ethical importance, but would like to
> >understand how it simplifies things? Seems to me that it
> >does not replace having entry criteria, and it complicates
> >the responsibility of the clinicians whose recruitment to
> >participating in trials Peto hopes to increase?
>
> What a coincidence. This is the other article that I am presenting at our
> journal club.
>
> As I understand it, Peto does indeed intend for this to completely replace
> entry criteria. Instead of the researchers restricting the medication to
> specific age groups, to a specific gender, etc., Peto intends for the
> clinicians who recruit patients to make all those judgements themselves.
>
> A simplistic example would be the study of a drug that was restricted to men
> or women beyond childbearing years because of the concern about teratogenic
> effects. Using Peto's guidelines, a clinician could still include a 30 year
> old woman in the study if she had a hysterectomy.
>
> Granted, the planners of the study could have written that exception in, but
> it is difficult to specify every possible contingency up front. The result,
> I suspect, is entry criteria that are far too restrictive in practice.
>
> It does make the job harder for the recruiting clinicians, but not any
> harder than the choices that they would have to make in the absence of a
> clinical trial.
>
> It's a good proposal in my opinion, but perhaps too radical to survive the
> scrutiny of most Institutional Review Boards.
>
> Steve Simon, [log in to unmask], Standard Disclaimer.
> STATS - Steve's Attempt to Teach Statistics: http://www.cmh.edu/stats
>
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