Elsevier

The Lancet

Volume 357, Issue 9253, 3 February 2001, Pages 373-380
The Lancet

Review
Reliable assessment of the effects of treatment on mortality and major morbidity, I: clinical trials

https://doi.org/10.1016/S0140-6736(00)03651-5Get rights and content

Summary

This two-part review is intended principally for practising clinicians who want to know why some types of evidence about the effects of treatment on survival, and on other major aspects of chronic disease outcome, are much more reliable than others. Although there are a few striking examples of treatments for serious disease which really do work extremely well, most claims for big improvements turn out to be evanescent. Unrealistic expectations about the chances of discovering large treatment effects could misleadingly suggest that evidence from small randomised trials or from non-randomised studies will suffice. By contrast, the reliable assessment of any more moderate effects of treatment on major outcomes—which are usually all that can realistically be expected from most treatments for most common serious conditions—requires studies that guarantee both strict control of bias (which, in general, requires proper randomisation and appropriate analysis, with no unduly data-dependent emphasis on specific parts of the overall evidence) and strict control of random error (which, in general, requires large numbers of deaths or of some other relevant outcome). Past failures to produce such evidence, and to interpret it appropriately, have already led to many premature deaths and much unnecessary suffering.

Section snippets

Proper randomisation

The fundamental reason for random allocation of treatment in clinical trials is to maximise the likelihood that each type of patient will have been allocated in similar proportions to the different treatment strategies being investigated.10 In a properly randomised trial, the decision to enter a patient is made irreversibly in ignorance of which trial treatments that patient will be allocated. Foreknowledge of the next treatment allocation could affect the decision to enter the patient, and

SUMMARY: The need for large-scale randomised evidence

In a world in which moderate effects of treatment on mortality or major morbidity are generally more plausible than large effects, claims of striking effects from small-scale randomised trials, and from other sources (including observational studies1, will often prove evanescent. The assumption that both a moderate difference or no difference may be plausible, and that an extreme difference is much less so, has surprisingly strong consequences for the interpretation of evidence from trials. In

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