Mixture of Finite Mixtures Model for Basket Trial

Fuente: arXiv
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Main Authors: Geng, Junxian, Zhou, Tianjian, Lin, Ruitao, Hu, Guanyu
Format: Preprint
Published: 2020
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_version_ 1866913108281262080
author Geng, Junxian
Zhou, Tianjian
Lin, Ruitao
Hu, Guanyu
author_facet Geng, Junxian
Zhou, Tianjian
Lin, Ruitao
Hu, Guanyu
contents With the recent paradigm shift from cytotoxic drugs to new generation of target therapy and immuno-oncology therapy during oncology drug developments, patients with various cancer (sub)types may be eligible to participate in a basket trial if they have the same molecular target. Bayesian hierarchical modeling (BHM) are widely used in basket trial data analysis, where they adaptively borrow information among different cohorts (subtypes) rather than fully pool the data together or doing stratified analysis based on each cohort. Those approaches, however, may have the risk of over shrinkage estimation because of the invalidated exchangeable assumption. We propose a two-step procedure to find the balance between pooled and stratified analysis. In the first step, we treat it as a clustering problem by grouping cohorts into clusters that share the similar treatment effect. In the second step, we use shrinkage estimator from BHM to estimate treatment effects for cohorts within each cluster under exchangeable assumption. For clustering part, we adapt the mixture of finite mixtures (MFM) approach to have consistent estimate of the number of clusters. We investigate the performance of our proposed method in simulation studies and apply this method to Vemurafenib basket trial data analysis.
format Preprint
id arxiv_https___arxiv_org_abs_2011_04135
institution arXiv
publishDate 2020
record_format arxiv
spellingShingle Mixture of Finite Mixtures Model for Basket Trial
Geng, Junxian
Zhou, Tianjian
Lin, Ruitao
Hu, Guanyu
Methodology
Applications
With the recent paradigm shift from cytotoxic drugs to new generation of target therapy and immuno-oncology therapy during oncology drug developments, patients with various cancer (sub)types may be eligible to participate in a basket trial if they have the same molecular target. Bayesian hierarchical modeling (BHM) are widely used in basket trial data analysis, where they adaptively borrow information among different cohorts (subtypes) rather than fully pool the data together or doing stratified analysis based on each cohort. Those approaches, however, may have the risk of over shrinkage estimation because of the invalidated exchangeable assumption. We propose a two-step procedure to find the balance between pooled and stratified analysis. In the first step, we treat it as a clustering problem by grouping cohorts into clusters that share the similar treatment effect. In the second step, we use shrinkage estimator from BHM to estimate treatment effects for cohorts within each cluster under exchangeable assumption. For clustering part, we adapt the mixture of finite mixtures (MFM) approach to have consistent estimate of the number of clusters. We investigate the performance of our proposed method in simulation studies and apply this method to Vemurafenib basket trial data analysis.
title Mixture of Finite Mixtures Model for Basket Trial
topic Methodology
Applications
url https://arxiv.org/abs/2011.04135