A Phase II Clinical Trial with Efficacy and Toxicity Outcomes and Baseline Covariates

Kristian Brock, Lucinda Billingham, Christina Yap, Gary Middleton

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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The experimental design presented here is motivated by a phase II clinical
trial called PePS2, investigating the efficacy and safety of an immunotherapy called pembrolizumab in a specific subgroup of lung cancer patients. Previous trials have shown that the probability of efficacy is correlated with particular patient variables. There are clinical trial designs that investigate co-primary efficacy and toxicity outcomes in phase II, but few that incorporate covariates.We present here the approach we developed for PePS2, latterly recognised to be a special case of a more general method originally presented by Thall, Nguyen and Estey. Their method incorporates covariates to conduct a dose-finding study but has been scarcely used in trials. Dosefinding is not required in PePS2 because a candidate dose has been widely tested. Starting from the most general case, we introduce our method as a novel refinement appropriate for use in phase II, and evaluate it using a simulation study. Our method shares information across patient cohorts. Simulations show it is more efficient than analysing the cohorts separately. Using the design in PePS2 with 60 patients to test the treatment in six cohorts determined by our baseline covariates, we can expect error rates typical of those used in phase II trials. However, we demonstrate that care must be taken when specifying the models for efficacy and toxicity because more
complex models require greater sample sizes for acceptable simulated performance.
Original languageEnglish
Title of host publicationBayesian Statistics
Subtitle of host publicationNew Challenges and New Generations
ISBN (Electronic)978-3-030-30611-3
ISBN (Print)978-3-030-30610-6
Publication statusPublished - 27 Nov 2019
EventInternational Conference on Bayesian Statistics in Action - Warwick, United Kingdom
Duration: 2 Jul 20183 Jul 2018

Publication series

NameSpringer Proceedings in Mathematics & Statistics
ISSN (Print)2194-1009
ISSN (Electronic)2194-1017


ConferenceInternational Conference on Bayesian Statistics in Action
Abbreviated titleBAYSM
Country/TerritoryUnited Kingdom


  • covariate
  • efficacy
  • phase II
  • toxicity
  • trial


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