Opportunities and challenges of clinical trials in cardiology using composite primary endpoints

TY - JOUR

T1 - Opportunities and challenges of clinical trials in cardiology using composite primary endpoints

AU - Rauch, Geraldine

AU - Rauch, Bernhard

AU - Schüler, Svenja

AU - Kieser, Meinhard

PY - 2015/1/26

Y1 - 2015/1/26

N2 - In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is intended to enlarge the expected effect size and thereby increase the power of the study. However, composite endpoints also come along with serious challenges and problems. On the one hand, composite endpoints may lead to difficulties during the planning phase of a trial with respect to the sample size calculation, as the expected clinical effect of an intervention on the composite endpoint depends on the effects on its single components and their correlations. This may lead to wrong assumptions on the sample size needed. Too optimistic assumptions on the expected effect may lead to an underpowered of the trial, whereas a too conservatively estimated effect results in an unnecessarily high sample size. On the other hand, the interpretation of composite endpoints may be difficult, as the observed effect of the composite does not necessarily reflect the effects of the single components. Therefore the demonstration of the clinical efficacy of a new intervention by exclusively evaluating the composite endpoint may be misleading. The present paper summarizes results and recommendations of the latest research addressing the above mentioned problems in the planning, analysis and interpretation of clinical trials with composite endpoints, thereby providing a practical guidance for users.

AB - In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is intended to enlarge the expected effect size and thereby increase the power of the study. However, composite endpoints also come along with serious challenges and problems. On the one hand, composite endpoints may lead to difficulties during the planning phase of a trial with respect to the sample size calculation, as the expected clinical effect of an intervention on the composite endpoint depends on the effects on its single components and their correlations. This may lead to wrong assumptions on the sample size needed. Too optimistic assumptions on the expected effect may lead to an underpowered of the trial, whereas a too conservatively estimated effect results in an unnecessarily high sample size. On the other hand, the interpretation of composite endpoints may be difficult, as the observed effect of the composite does not necessarily reflect the effects of the single components. Therefore the demonstration of the clinical efficacy of a new intervention by exclusively evaluating the composite endpoint may be misleading. The present paper summarizes results and recommendations of the latest research addressing the above mentioned problems in the planning, analysis and interpretation of clinical trials with composite endpoints, thereby providing a practical guidance for users.

KW - Journal Article

U2 - 10.4330/wjc.v7.i1.1

DO - 10.4330/wjc.v7.i1.1

M3 - SCORING: Journal article

C2 - 25632312

VL - 7

SP - 1

EP - 5

JO - WORLD J CARDIOL

JF - WORLD J CARDIOL

SN - 1949-8462

IS - 1

ER -