To which groups of patients can the results of clinical trials be applied? This question is often inappropriately answered by reference to the trial entry criteria. Instead, the benefit and harm (adverse events, discomfort of treatment, etc) of treatment could be assessed separately for individual patients. Patients at greatest risk of a disease will have the greatest net benefit as benefit to patients usually increases with risk while harm remains comparatively fixed. To assess net benefit, the relative risks should come from (a meta-analysis of) randomised trials; the risk in individual patients should come from multivariate risk equations derived from cohort studies. However, before making firm conclusions, the assumptions of fixed adverse effects and constant reduction in relative risk need to be checked.

Should all patients with acute myocardial infarct receive streptokinase? Should all patients with non-valvar atrial fibrillation receive warfarin? Such questions are best answered by assessing benefits and risks in each patient rather than focusing on the inclusion and exclusion criteria of the trial. For example, patients with a history of peptic ulcer were often excluded from thrombolytic trials because it would be unethical to put such patients at risk of major bleeding episodes, given the lack of proved benefit. However, now that we know the size of the benefit--about three deaths saved for every 100 patients treated1--clinicians must make an informed decision that weighs this benefit against the potential for harm in patients with ulcers.

Relying on the eligibility criteria for clinical trials is both erroneous and limiting. A too restrictive generalisation needs to be guarded against, and we are advised to ask, “Are the patients in this study so different from my patients that I could not apply the study results?”2 This is good advice, but how then do we decide when a …