John Worrall (LSE): “Placebo versus Active Controlled Clinical Trials: the FDA’s folly?”

Abstract: Suppose that a treatment T for some medical condition C is already available and is universally recognized to be effective; and suppose that some new treatment T´ for that same condition C is under investigation. From the scientific point of view (that is, laying aside pragmatic issues such as, perhaps, the relative cost of the two treatments) there would, it seems, be no interest in testing the experimental treatment T´ against placebo. What the physician wants to know is whether T´ is better than (or, at any rate, at least as good as) the already-known-to-be-effective T not whether it is merely better than placebo. Accordingly, trials on T´ should, one would have thought, be “active-controlled” (meaning that those in the control group receive the active treatment T) rather than “placebo-controlled”. (There also seem to be clear ethical objections to conducting placebo-controlled trials in such a situation since those in the control group in such trials are knowingly given a treatment that is less effective than another available treatment.)

It is, therefore, at least prima facie surprising that thousands and thousands of placebo-controlled trials are still performed even for conditions where an ‘active’ treatment is available. Part of the surprise dissipates once one reflects on the greed of ‘Big Pharma’.  But, even allowing for that, there is a remaining (very) surprising fact: namely that regulatory bodies, most notably the US Federal Drug Administration, endorse carrying out placebo – controlled trials when an active treatment is already available – indeed this is often made a necessary requirement for FDA approval of the treatment concerned.

What explains this apparently mysterious attitude of the FDA’s?  The answer is that it has been convinced by a methodological argument called the ‘assay sensitivity’ argument which purports to establish that active controlled trials are subject to methodological defects not present in placebo controlled trials. I analyse that argument and show that, although it seems to have proved seductive, the argument in fact rests on some elementary logico-methodological mistakes.  I thus vindicate the commonsense view that there is never any scientific reason to perform placebo-controlled trials when an ‘active’ treatment is already available.

[If there is time, I will also investigate the ethical issues that have arisen in connection with the assay sensitivity argument and the acceptability of performing placebo-controlled trials when an active treatment is available.]

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