Bin-CE: A comprehensive web application to decide upon the best set of outcomes to be combined in a binary composite endpoint

Josep Ramon Marsal, Ignacio Ferreira-González, Aida Ribera, Gerard Oristrell, Jose Ignacio Pijoan, David García-Dorado

Research output: Contribution to journalArticleResearch

1 Citation (Scopus)


© 2018 Marsal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The estimation of the Sample Size Requirement (SSR) when using a binary composite endpoint (i.e. two or more outcomes combined in a unique primary endpoint) is not trivial. Besides information about the rate of events for each outcome, information about the strength of association between the outcomes is crucial, since it can determine an increase or decrease of the SSR. Specifically, the greater the strength of association between outcomes the higher the SSR. We present Bin-CE, a free tool to assist clinicians for computing the SSR for binary composite endpoints. In a first step, the user enters a set of candidate outcomes, the assumed rate of events for each outcome and the assumed effect of therapy on each outcome. Since the strength of the association between outcomes is usually unknown, a semi-parametric approach linking the a priori clinical knowledge of the potential degree of association between outcomes with the exact values of these parameters was programmed with Bin-CE. Bin-CE works with a recursive algorithm to choose the best combination of outcomes that minimizes the SSR. In addition, Bin-CE computes the sample size using different algorithms and shows different figures plotting the magnitude of the sample size reduction, and the effect of different combinations of outcomes on the rate of the primary endpoint. Finally, Bin-CE is programmed to perform sensitivity analyses. This manuscript presents the mathematic bases and introduces the reader to the use of Bin-CE using a real example.
Original languageEnglish
Article numbere0209000
JournalPLoS ONE
Publication statusPublished - 1 Dec 2018


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