Thanks for spotting my typo! You are quite correct that should
read 'the uncertainty principle applies as an INclusion criteria prior
to randomisation'.
My apologies to the list.
Regards
Anne Leigh Brown
Date sent: Mon, 20 Aug 2001 16:00:42 -0400
Send reply to: "Djulbegovic, Benjamin" <[log in to unmask]>
From: "Djulbegovic, Benjamin" <[log in to unmask]>
Subject: Re: FW: uncertainty principle
To: [log in to unmask]
> This is a bit puzzling. Uncertainty should imply ELIGIBILITY, and not
> other way around. bd
>
> -----Original Message-----
> From: Anne Leigh Brown [mailto:[log in to unmask]]
> Sent: Monday, August 20, 2001 4:37 AM
> To: [log in to unmask]
> Subject: Re: FW: uncertainty principle
>
>
> Dear Jeanne
> I see that your example of the uncertainty principle is from the
> protocol from the Third International Stroke Trial (IST-3), a double
> blind placebo controlled trial of rt-PA for acute stroke. I can
> confirm that in this trial the uncertainty principle only applies as
> an exclusion criteria prior to randomisation. Any individual
> randomised into the trial will be followed-up. If for any reason they
> did not receive the trial treatment they would still be followed up
> and the circumstances would be fully documented. All analyses are by
> intention-to-treat. As before please contact me if you require any
> further information. Regards Anne Leigh Brown
>
>
>
> Date sent: Fri, 17 Aug 2001 15:59:19 -0400
>
> Send reply to: [log in to unmask]
> From: Jeanne Lenzer <[log in to unmask]>
> Subject: FW: uncertainty principle
> To: [log in to unmask]
>
> > -----Original Message-----
> > From: Jeanne Lenzer [mailto:[log in to unmask]]
> > Sent: Friday, August 17, 2001 3:44 PM
> > To: [log in to unmask]
> > Subject: RE: uncertainty principle
> >
> > Hi Victor -
> >
> > Thank you very much for your explanation. It seems to me (and
> > forgive me, I'm merely a journalist here trying to learn) - but it
> > seems to me that what you say is true - but that it may not be
> > relevant to the study protocol that included that paragraph.
> >
> > The uncertainty principle, it seems to me, is what should be
> > operative in order to determine whether a study should be undertaken
> > at all. Do we know if drug A is definitely better than placebo? If
> > we don't know the answer to that, then and only then, is a study
> > ethical. However, once we determine that we are uncertain and a
> > study is ethical - to allow clinicians to remove patients from
> > randomization still seems to be risky to me and I wonder about that
> > undermining the study's genuine randomness.
> >
> > For example, what if a clinician has a bias that the drug must work
> > better than placebo and therefore chooses to pull out a number of
> > the "sicker" patients but not the less sick patients because he or
> > she thinks "it's really important that my patient get the active
> > drug"? Could that change the spectrum of patients receiving
> > treatment vs. non-treatment? Also, what if the researcher has
> > vested interests (is receiving drug company funding) - could she or
> > he then (consciously or unconsciously) pull patients out of the
> > randomization process in a manner that influences the process? I
> > guess a lot of this depends on when the patient is pulled - before
> > or after randomization? But even then, prior exclusion of all
> > "really sick" patients could affect the process? Or am I hopelessly
> > lost?
> >
> > Thanks much
> > jeanne
> >
> > -----Original Message-----
> > From: [log in to unmask] [mailto:[log in to unmask]]
> > Sent: Friday, August 17, 2001 2:55 PM
> > To: [log in to unmask]
> > Subject: RE: uncertainty principle
> >
> >
> > This is not liberal, it is ethical. If there is no doubt that
> > active treatment is in the best interest of the patient then not
> > offering it to her would be substandard care (same for clearly
> > contraindicated medication). Only those patient-physician duets that
> > are certain that they do not know whether treatment A is better than
> > treatment B are in a reasonable situation to join the study. There
> > is no way around this.
> > The dangers of not following this principle is patient desertion,
> > off-study use of study medication, and other forms of noise that
> > will limit the ability of the study to show a treatment effect
> > resulting in a monumental waste of time and resources for all
> > involved. Does this answer your question? V
> >
> > > ----------
> > > From: Jeanne Lenzer[SMTP:[log in to unmask]]
> > > Reply To: [log in to unmask]
> > > Sent: Friday, August 17, 2001 1:32 PM
> > > To: [log in to unmask]
> > > Subject: uncertainty principle
> > >
> > > Could anyone explain the pros and cons of the following:
> > >
> > > Uncertainty principle (absence of proof): Further inclusion and
> > > exclusion criteria are not specified precisely but are guided by
> > > the uncertainty principle (or absence of proof for that particular
> > > patient). If, for whatever reason, the clinician is convinced that
> > > a patient fulfilling the above criteria should be treated, that
> > > patient should be given open label drug and not randomized. If the
> > > clinician is convinced that a patient should not be treated (for
> > > whatever reason), the patient should not be included in the trial.
> > > Only those patients who fulfill the eligibility criteria AND for
> > > whom the clinician is still substantially uncertain about the
> > > balance of risks and benefits of active drug should be randomized.
> > >
> > > Can this kind of enrollment liberalism cause a failure of true
> > > randomization? Does it introduce spectrum and other biases?
> > >
> > > Thank you any and all for any insight you can give this underfed
> > > journalist.
> > >
> > > Jeanne Lenzer
> > > Freelance writer
> > > 191 Otens Rd.
> > > Ellenville, NY 12428
> > > USA
> > > Office phone: 845-647-3670
> > > Office fax: 845-647-3670
> > > Cell phone pager: 914-399-5001
> > > [log in to unmask]
> > >
> > >
> > >
>
>
>
> ________________________________________
>
> Anne Leigh Brown
> Neurosciences Trials Unit
> University of Edinburgh
> Bramwell Dot Building
> Western General Hospital
> Crewe Road
> Edinburgh EH4 2XU
> UK
> e-mail: [log in to unmask]
> Telephone: 0131-537-2930
> Fax: 0131-332-5150
> ________________________________________
________________________________________
Anne Leigh Brown
Neurosciences Trials Unit
University of Edinburgh
Bramwell Dot Building
Western General Hospital
Crewe Road
Edinburgh EH4 2XU
UK
e-mail: [log in to unmask]
Telephone: 0131-537-2930
Fax: 0131-332-5150
________________________________________
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