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Adaptive seamless clinical trials using early outcomes for treatment or subgroup selection : methods, simulation model and their implementation in R
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Friede, Tim, Stallard, Nigel and Parsons, Nicholas R. (2020) Adaptive seamless clinical trials using early outcomes for treatment or subgroup selection : methods, simulation model and their implementation in R. Biometrical Journal, 62 (5). doi:10.1002/bimj.201900020
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Official URL: https://doi.org/10.1002/bimj.201900020
Abstract
Adaptive seamless designs combine confirmatory testing, a domain of phase III trials, with features such as treatment or subgroup selection, typically associated with phase II trials. They promise to increase the efficiency of development programmes of new drugs, for example, in terms of sample size and/or development time. It is well acknowledged that adaptive designs are more involved from a logistical perspective and require more upfront planning, often in the form of extensive simulation studies, than conventional approaches. Here, we present a framework for adaptive treatment and subgroup selection using the same notation, which links the somewhat disparate literature on treatment selection on one side and on subgroup selection on the other. Furthermore, we introduce a flexible and efficient simulation model that serves both designs. As primary endpoints often take a long time to observe, interim analyses are frequently informed by early outcomes. Therefore, all methods presented accommodate interim analyses informed by either the primary outcome or an early outcome. The R package asd, previously developed to simulate designs with treatment selection, was extended to include subgroup selection (so‐called adaptive enrichment designs). Here, we describe the functionality of the R package asd and use it to present some worked‐up examples motivated by clinical trials in chronic obstructive pulmonary disease and oncology. The examples both illustrate various features of the R package and provide insights into the operating characteristics of adaptive seamless studies.
| Item Type: | Journal Article | ||||||||
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| Subjects: | R Medicine > R Medicine (General) | ||||||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of Medicine > Warwick Medical School > Health Sciences > Statistics and Epidemiology Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Clinical trials, Adaptive sampling (Statistics), Clinical trials -- Statistical methods, Clinical trials -- Design | ||||||||
| Journal or Publication Title: | Biometrical Journal | ||||||||
| Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | ||||||||
| ISSN: | 0323-3847 | ||||||||
| Official Date: | September 2020 | ||||||||
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| Volume: | 62 | ||||||||
| Number: | 5 | ||||||||
| DOI: | 10.1002/bimj.201900020 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access | ||||||||
| RIOXX Funder/Project Grant: |
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