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arXiv · 2409.10352

Partial Ordering Bayesian Logistic Regression Model for Phase I Combination Trials and Computationally Efficient Approach to Operational Prior Specification

Weishi Chen·Pavel Mozgunov
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Abstract

Recent years have seen increased interest in combining drug agents and/or schedules. Several methods for Phase I combination-escalation trials are proposed, among which, the partial ordering continual reassessment method (POCRM) gained great attention for its simplicity and good operational characteristics. However, the one-parameter nature of the POCRM makes it restrictive in more complicated settings such as the inclusion of a control group. This paper proposes a Bayesian partial ordering logistic model (POBLRM), which combines partial ordering and the more flexible (than CRM) two-parameter logistic model. Simulation studies show that the POBLRM performs similarly as the POCRM in non-randomised settings. When patients are randomised between the experimental dose-combinations and a control, performance is drastically improved. Most designs require specifying hyper-parameters, often chosen from statistical considerations (operational prior). The conventional "grid search'' calibration approach requires large simulations, which are computationally costly. A novel "cyclic calibration" has been proposed to reduce the computation from multiplicative to additive. Furthermore, calibration processes should consider wide ranges of scenarios of true toxicity probabilities to avoid bias. A method to reduce scenarios based on scenario-complexities is suggested. This can reduce the computation by more than 500 folds while remaining operational characteristics similar to the grid search.

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Weishi Chen, Pavel Mozgunov. 2024-09-16. Partial Ordering Bayesian Logistic Regression Model for Phase I Combination Trials and Computationally Efficient Approach to Operational Prior Specification. https://doi.org/10.1002/sim.70621

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