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When are randomised trials unnecessary? Picking signal from noise

BMJ 2007; 334 doi: (Published 15 February 2007) Cite this as: BMJ 2007;334:349

This article has a correction. Please see:

  1. Paul Glasziou, professor1,
  2. Iain Chalmers, editor2,
  3. Michael Rawlins, honorary professor3,
  4. Peter McCulloch, reader4
  1. 1Centre for Evidence-Based Medicine, Department of Primary Health Care, University of Oxford, Oxford OX3 7LF
  2. 2James Lind Library, James Lind Initiative, Oxford OX2 7LG
  3. 3London School of Hygiene and Tropical Medicine, London WC1E 7HT
  4. 4Nuffield Department of Surgery, John Radcliffe Hospital, Oxford OX3 9DU
  1. Correspondence to: P Glasziou

    Although randomised trials are widely accepted as the ideal way of obtaining unbiased estimates of treatment effects, some treatments have dramatic effects that are highly unlikely to reflect inadequately controlled biases. We compiled a list of historical examples of such effects and identified the features of convincing inferences about treatment effects from sources other than randomised trials. A unifying principle is the size of the treatment effect (signal) relative to the expected prognosis (noise) of the condition. A treatment effect is inferred most confidently when the signal to noise ratio is large and its timing is rapid compared with the natural course of the condition. For the examples we considered in detail the rate ratio often exceeds 10 and thus is highly unlikely to reflect bias or factors other than a treatment effect. This model may help to reduce controversy about evidence for treatments whose effects are so dramatic that randomised trials are unnecessary.

    The relation between a treatment and its effect is sometimes so dramatic that bias can be ruled out as an explanation. Paul Glasziouand colleagues suggest how to determine when observations speak for themselves


    • We thank Abdelhamid Attia, Benjamin Djulbegovic, Hywel Williams, Jan Vandenbroucke, Olaf Dekkers, Dave Sackett, Jonathan Meakins, Ruth Gilbert, Amanda Burls, Ken Fleming, and the members of the Evidence-Based Health Care email list for help with examples and comments on earlier drafts of this paper.

    • Contributors and sources: All authors have been involved in both clinical trials and clinical practice and the links between these. PG and IC conceived the study; all authors contributed to compiling the examples used for analysis, and development of the concepts and writing of the paper. PG is guarantor.

    • Competing interests: None declared.

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