For what it's worth:
Moore, T. (1995). Deadly Medicine: Why Tens of Thousands of Heart Patients Died in America's Worst Drug Disaster. New York, Simon & Schuster.
Describes the complicity of the FDA and top academic cardiologists in approving anti-arrythmic medicines first in the absence of evidence either for saftey or effectiveness and then in the face of good evidence of the harm the drugs were eventually recognized as causing.
Jim
James M. Walker, MD, FACP
Chief Medical Information Officer
Geisinger Health System
The best way to predict the future is to invent it.
- Alan Kay
>>> Catherine Will 03/07/11 3:31 PM >>>
Hi Jeremy
Interesting question! I'm sorry I can't help with your specific case but would be intrigued to have further discussion of the place of mechanistic thinking (with or without other evidence) in both decisions about when to start particular trials, and how to interpret trial findings.
In terms of pharmaceuticals, especially commercial drug development, seems there is quite a lot of regulation of the former case, but not a lot of discussion of the general issue of trial interpretation, which ends up being about what claims may be made as part of marketing.
But from the perspective of practitioners, when do trials themselves stand as evidence on pathophysiology (disprove a mechanism?) and when they are read more 'modestly' as evidence for the effectiveness (perhaps through unknown pathways) of particular interventions?
In most cases they are used as both, but seems to me that sometimes clinicians (including guideline writers) do have difficulty in finding the right mix of these two readings. For example, do you extrapolate from a trial of cholesterol reduction in secondary prevention to primary prevention or from a trial in the middle aged to the elderly? Does it worry you that a trial of acupuncture shows pain reduction if you don't have a theory about why it has this effect?
Catherine.
Dr Catherine Will
School of Law, Politics and Sociology
University of Sussex
Brighton
BN1 9SP
Tel: 01273 678449
On 4 Mar 2011, at 12:07, Jeremy Howick wrote:
>> Dear All,
>>
>> The CAST (randomized) trial revealed that treatments introduced solely on
>> the basis of 'pathophysiologic rationale' (mechanisms) can be deadly. Does
>> anyone know whether there was any OBSERVATIONAL evidence supporting the
>> effectiveness of antiarrhythmic drugs for reducing mortality (obviously
>> before CAST)?
>>
>> Thank you!
>>
>> Jeremy
>>
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