Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Adaptive seamless clinical trials using early outcomes for treatment or subgroup selection : methods, simulation model and their implementation in R

Tools
- Tools
+ Tools

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

[img]
Preview
PDF
WRAP-adaptive-seamless-clinical-trials-using-early-outcomes-treatment-subgroup-selection-Stallard-2020.pdf - Published Version - Requires a PDF viewer.
Available under License Creative Commons Attribution 4.0.

Download (451Kb) | Preview
[img] PDF
WRAP-adaptive-seamless-clinical-trials-outcomes-Stallard-2020.pdf - Accepted Version
Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer.

Download (846Kb)
Official URL: https://doi.org/10.1002/bimj.201900020

Request Changes to record.

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
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
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
Dates:
DateEvent
September 2020Published
2 March 2020Available
12 January 2020Accepted
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:
Project/Grant IDRIOXX Funder NameFunder ID
G1001344[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
Related URLs:
  • Publisher

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item
twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us