- •Studies often combine several events into a single study outcome, the composite endpoint.
- •Using composite endpoints reduces the sample size or follow-up period required to demonstrate the effectiveness of an intervention.
- •To avoid misleading conclusions about the effectiveness of an intervention, it is important to ascertain that the clinical importance, the frequency of events, and the effect of the intervention on each component of the composite endpoint are similar.
|Outcome||Rosiglitazone n = 2,635||Placebo n = 2,634||Hazard Ratio (95% CI)||P|
|Diabetes||280 (10.6%)||658 (25.0%)||0.38 (0.33, 0.44)||<0.0001|
|Death||30 (1.1%)||33 (1.3%)||0.91 (0.55, 1.49)||0.7|
|Death or diabetes (composite)||306 (11.6%)||686 (26.0%)||0.40 (0.35, 0.46)||<0.0001|
- 1.The components of the composite endpoint must be of similar clinical importance to patients. For example, in Table 1, death was clearly more important than diabetes, so these two outcomes should not have been combined into a composite endpoint. In contrast, a composite outcome of death, stroke, or myocardial infarction would be more acceptable because these component outcomes are of arguably similar importance.
- 2.The frequency of the occurrence of the components over the same time period must be similar; otherwise, the effect on the composite will be largely determined by the predominant event. In Table 1, 938 patients in the DREAM study developed diabetes, whereas only 63 deaths were recorded. This means the reduction in the composite was largely (or solely) determined by the reduction in diabetes (Table 1).
- 3.Finally, the effect of the treatment must be similar for each component of the composite. In Table 1, the outcome of diabetes is decreased in the rosiglitazone group, but there is no difference in the outcome of death. In such a situation, the reduction in the composite outcome (26.0% vs. 11.6%, P < 0.0001) could lead to a misleading suggestion that both events decreased.
- Composite endpoints in clinical trials.Rev Esp Cardiol. 2008; 61: 283-290
- For the DREAM trial investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomized controlled trial.Lancet. 2006; : 1096-1105
- Validity of composite endpoints in clinical trials.BMJ. 2005; 330: 594-596