Wheeler, GM;
Sweeting, M;
Mander, A;
(2019)
A Bayesian model‐free approach to combination therapy phase I trials using censored time‐to‐toxicity data.
Journal of the Royal Statistical Society: Series C (Applied Statistics)
, 68
(2)
pp. 309-329.
10.1111/rssc.12323.
Preview |
Text
Wheeler_A Bayesian model-free approach to combination therapy phase I trials using censored time-to-toxicity data_VoR.pdf - Published Version Download (970kB) | Preview |
Abstract
The product of independent beta probabilities escalation design for dual agent phase I dose escalation trials is a Bayesian model‐free approach for identifying multiple maximum tolerated dose combinations of novel combination therapies. Despite only being published in 2015, the design has been implemented in at least two oncology trials. However, these trials require patients to have completed follow‐up before clinicians can make dose escalation decisions. For trials of radiotherapy or advanced therapeutics, this may lead to impractically long trial durations due to late‐onset treatment‐related toxicities. We extend the product of independent probabilities escalation design to use censored time‐to‐event toxicity outcomes for making dose escalation decisions. We show via comprehensive simulation studies and sensitivity analyses that trial duration can be reduced by up to 35%, particularly when recruitment is faster than expected, without compromising on other operating characteristics.
| Type: | Article |
|---|---|
| Title: | A Bayesian model‐free approach to combination therapy phase I trials using censored time‐to‐toxicity data |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/rssc.12323 |
| Publisher version: | https://doi.org/10.1111/rssc.12323 |
| Language: | English |
| Additional information: | © 2018 The Authors Journal of the Royal Statistical Society: Series C (Applied Statistics) Published by John Wiley & Sons Ltd on behalf of the Royal Statistical Society. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Adaptive designs, Bayesian methods, Clinical trials, Dose escalation, Model‐free approach, Model‐free approach |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10058098 |
Archive Staff Only
 |
View Item |
