Monday, May 18, 2009

More from Dr. Rich on Comparative Effectiveness Research (CER)

Dr. Rich’s latest post on CER eloquently reinforces some of my points. Let’s start with the premise that bias in research isn’t exclusive to industry funded research. Dr. Rich writes:

While in laboratory research the elimination of bias is always a challenging endeavor, DrRich believes that in clinical research it is an ultimately futile endeavor.

That’s because we’re all biased and conflicted. The loudest voices in this debate, the pharmascolds, are not honest about that fact.

He goes on:

And for this reason, anyone claiming to have performed unbiased clinical research is either blowing smoke up your nether regions, or is too ignorant about the realities of clinical research to be allowed to perform it.

A little later in the post he says:

The sad truth is that the results of RCTs are invariably dependent on the bias built into their design, and even if internally they are statistically legitimate, they can often send us down the wrong path.

More important though is the fact that compared to placebo controlled trials this bias is magnified in CER (which, before it was given the catchy and politically charged new name, is what we used to call head-to-head trials). The reason for this is, as I explained with numerous examples, is that there are more abundant opportunities to tweak the design of head-to-head trials than of placebo controlled trials. So the bias inherent in all clinical research finds greater opportunity in CER.

He goes on to note:

Those who design RCTs (the smart ones, at least) know this. Like smart trial attorneys, they know the answer before they ever dare to ask the question. So they tailor their “question” in such a way as to yield the answer they want to get.

This is particularly true of the new government program of CER. In a recent post I cited many statements by the promoters of CER which illustrate the fact that they already know what the “research” will show: it will favor cheaper treatments.

Dr. Rich describes how bias can creep into design:

So, for instance, if you are a payer and want to limit the use of an expensive therapy, you design your RCT so that enrolled patients likely to respond to the therapy are diluted with a broad population of enrolled patients much less likely to respond, to assure that the average response of the whole population will be quite small. (In many instances the clinical characteristics of the likely responders and the likely non responders will be reasonably apparent.)

Among many other studies Dr. Rich might have been describing ALLHAT, a comparative effectiveness hypertension trial in which an ACE inhibitor could not, in the study design, be administered in a pharmacologically rational manner. Specifically, it could not be combined with diuretics or other medications known to produce a synergistic effect which, though a disadvantage in all patients, was previously known to be particularly adverse in African Americans, who made up 35% of the ALLHAT population. The deck was thus stacked in favor of thiazide diuretics.

But here’s the bomb in Dr. Rich’s post:

The apparently widespread notion that industry-sponsored research is invariably biased, while government-sponsored research is entirely objective - and that therefore, the only thing we need to assure accurate research is to have it all conducted by the government - is astoundingly naive.

‘Nuff said!

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