| Title |
Choice of futility boundaries for group sequential designs with two endpoints
|
|---|---|
| Published in |
BMC Medical Research Methodology, August 2017
|
| DOI | 10.1186/s12874-017-0387-4 |
| Pubmed ID | |
| Authors |
Svenja Schüler, Meinhard Kieser, Geraldine Rauch |
| Abstract |
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. 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. 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. 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. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Venezuela, Bolivarian Republic of | 1 | 50% |
| United Kingdom | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 31 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 11 | 35% |
| Other | 3 | 10% |
| Student > Doctoral Student | 3 | 10% |
| Student > Bachelor | 3 | 10% |
| Student > Ph. D. Student | 3 | 10% |
| Other | 2 | 6% |
| Unknown | 6 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 23% |
| Mathematics | 5 | 16% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
| Decision Sciences | 2 | 6% |
| Biochemistry, Genetics and Molecular Biology | 1 | 3% |
| Other | 4 | 13% |
| Unknown | 10 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 August 2017.
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#15,475,586
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Outputs from BMC Medical Research Methodology
#1,521
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Outputs of similar age from BMC Medical Research Methodology
#29
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