eprintid: 23339
rev_number: 11
eprint_status: archive
userid: 1589
dir: disk0/00/02/33/39
datestamp: 2017-08-15 13:00:31
lastmod: 2024-01-18 23:42:46
status_changed: 2017-08-15 13:00:31
type: article
metadata_visibility: show
creators_name: Schüler, Svenja
creators_name: Kieser, Meinhard
creators_name: Rauch, Geraldine
title: Choice of futility boundaries for group sequential designs with two endpoints
subjects: ddc-610
divisions: i-911800
abstract: Background: In clinical trials, the opportunity for an early stop during an interim analysis (either for efficacy or for futility) may relevantly save time and financial resources. This is especially important, if the planning assumptions required for power calculation are based on a low level of evidence. For example, when including two primary endpoints in the confirmatory analysis, the power of the trial depends on the effects of both endpoints and on their correlation. Assessing the feasibility of such a trial is therefore difficult, as the number of parameter assumptions to be correctly specified is large. For this reason, so-called ‘group sequential designs’ are of particular importance in this setting. Whereas the choice of adequate boundaries to stop a trial early for efficacy has been broadly discussed in the literature, the choice of optimal futility boundaries has not been investigated so far, although this may have serious consequences with respect to performance characteristics.   Methods: In this work, we propose a general method to construct ‘optimal’ futility boundaries according to predefined criteria. Further, we present three different group sequential designs for two endpoints applying these futility boundaries. Our methods are illustrated by a real clinical trial example and by Monte-Carlo simulations.   Results: By construction, the provided method of choosing futility boundaries maximizes the probability to correctly stop in case of small or opposite effects while limiting the power loss and the probability of stopping the study ‘wrongly’. Our results clearly demonstrate the benefit of using such ‘optimal’ futility boundaries, especially compared to futility boundaries commonly applied in practice.   Conclusions: As the properties of futility boundaries are often not considered in practice and unfavorably chosen futility boundaries may imply bad properties of the study design, we recommend assessing the performance of these boundaries according to the criteria proposed in here.
date: 2017
publisher: BioMed Central; Springer
id_scheme: DOI
ppn_swb: 1654673226
own_urn: urn:nbn:de:bsz:16-heidok-233392
language: eng
bibsort: SCHULERSVECHOICEOFFU2017
full_text_status: public
publication: BMC Medical Research Methodology
volume: 17
number: 119
place_of_pub: London; Berlin; Heidelberg
pagerange: 1-10
issn: 1471-2288
citation:   Schüler, Svenja ; Kieser, Meinhard ; Rauch, Geraldine  (2017) Choice of futility boundaries for group sequential designs with two endpoints.  BMC Medical Research Methodology, 17 (119).  pp. 1-10.  ISSN 1471-2288     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/23339/1/12874_2017_Article_387.pdf