[Combined endpoints].
The use of a combined (composite) endpoint as a primary outcome in clinical studies offers many advantages, e.g., increased statistical efficiency, smaller sample sizes, shorter study completion times, and the possibility for a summary measure of different treatment effects. However, basic clinical and statistical requirements need to be respected in order to obtain valid results and to avoid difficulties in their interpretation later. Each component of a combined endpoint must be clinically meaningful. Patients must be followed up until death or to the planned end of the trial; these rules also apply to premature treatment withdrawal or after occurrence of the first pre-defined component event. All components of the composite endpoint need to be analysed separately in order to find out how they contribute to the overall result and to avoid the masking of negative effects on one or more components. Difficulties in interpretation may arise when the results for single components of the combined endpoint head in opposite directions, and when "hard" clinical outcomes are combined with "soft" endpoints, particularly if the latter occur much more frequently but are of minor clinical relevance.
Kleist
Peter
P
GlaxoSmithKline AG, Münchenbuchsee, Schweiz. peter.m.kleist@gsk.com
D006801:Humans; D011340:Problem Solving; D015203:Reproducibility of Results; D012107:Research Design / Q000592:standards*; D016896:Treatment Outcome