Abstract
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.
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 language | English |
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Title of host publication | Bayesian Statistics |
Subtitle of host publication | New Challenges and New Generations |
Publisher | Springer |
Pages | 125-133 |
ISBN (Electronic) | 978-3-030-30611-3 |
ISBN (Print) | 978-3-030-30610-6 |
Publication status | Published - 27 Nov 2019 |
Event | International Conference on Bayesian Statistics in Action - Warwick, United Kingdom Duration: 2 Jul 2018 → 3 Jul 2018 |
Publication series
Name | Springer Proceedings in Mathematics & Statistics |
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Publisher | Springer |
Volume | 296 |
ISSN (Print) | 2194-1009 |
ISSN (Electronic) | 2194-1017 |
Conference
Conference | International Conference on Bayesian Statistics in Action |
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Abbreviated title | BAYSM |
Country/Territory | United Kingdom |
City | Warwick |
Period | 2/07/18 → 3/07/18 |
Keywords
- covariate
- efficacy
- phase II
- toxicity
- trial