Does randomization control for ‘lack of balance’?

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Lars Pålsson Syll
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Does randomization control for ‘lack of balance’?

Mike Clarke, the Director of the Cochrane Centre in the UK, for example, states on the Centre’s Web site: ‘In a randomized trial, the only difference between the two groups being compared is that of most interest: the intervention under investigation’.

This seems clearly to constitute a categorical assertion that by randomizing, all other factors — both known and unknown — are equalized between the experimental and control groups; hence the only remaining difference is exactly that one group has been given the treatment under test, while the other has been given either a placebo or conventional therapy; and hence any observed difference in outcome between the two groups in a randomized trial (but only in a randomized trial) must be the effect of the treatment under test.

Clarke’s claim is repeated many times elsewhere and is widely believed. It is admirably clear and sharp, but it is clearly unsustainable … Clearly the claim taken literally is quite trivially false: the experimental group contains Mrs Brown and not Mr Smith, whereas the control group contains Mr Smith and not Mrs Brown, etc. Some restriction on the range of differences being considered is obviously implicit here; and presumably the real claim is something like that the two groups have the same means and distributions of all the [causally?] relevant factors. Although this sounds like a meaningful claim, I am not sure whether it would remain so under analysis … And certainly, even with respect to a given (finite) list of potentially relevant factors, no one can really believe that it automatically holds in the case of any particular randomized division of the subjects involved in the study. Although many commentators often seem to make the claim … no one seriously thinking about the issues can hold that randomization is a sufficient condition for there to be no difference between the two groups that may turn out to be relevant …

In sum, despite what is often said and written, no one can seriously believe that having randomized is a sufficient condition for a trial result to be reasonably supposed to reflect the true effect of some treatment. Is randomizing a necessary condition for this? That is, is it true that we cannot have real evidence that a treatment is genuinely effective unless it has been validated in a properly randomized trial? Again, some people in medicine sometimes talk as if this were the case, but again no one can seriously believe it. Indeed, as pointed out earlier, modern medicine would be in a terrible state if it were true. As already noted, the overwhelming majority of all treatments regarded as unambiguously effective by modern medicine today — from aspirin for mild headache through diuretics in heart failure and on to many surgical procedures — were never (and now, let us hope, never will be) ‘validated’ in an RCT.

John Worrall

For more on the question of ‘balance’ in randomized experiments, this collection of papers in Social Science & Medicine gives many valuable insights.