Bayesian methods for the analysis of early‐phase oncology basket trials with information borrowing across cancer types

Prognosis modeling plays an important role in cancer studies. With the development of omics profiling, extensive research has been conducted to search for prognostic markers for various cancer types. However, many of the existing studies share a common limitation by only focusing on a single cancer type and suffering from a lack of sufficient information. With potential molecular similarity across cancer types, one cancer type may contain information useful for the analysis of other types. The integration of multiple cancer types may facilitate information borrowing so as to more comprehensively and more accurately describe prognosis. In this study, we conduct marginal and joint integrative analysis of multiple cancer types, effectively introducing integration in the discovery process. For accommodating high dimensionality and identifying relevant markers, we adopt the advanced penalization technique which has a solid statistical ground. Gene expression data on nine cancer types from The Cancer Genome Atlas (TCGA) are analyzed, leading to biologically sensible findings that are different from the alternatives. Overall, this study provides a novel venue for cancer prognosis modeling by integrating multiple cancer types.

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A Bayesian basket trial design using a calibrated Bayesian hierarchical model

Clinical Trials ◽

10.1177/1740774518755122 ◽

2018 ◽

Vol 15 (2) ◽

pp. 149-158 ◽

Cited By ~ 24

Author(s):

Yiyi Chu ◽

Ying Yuan

Keyword(s):

Hierarchical Model ◽

Treatment Effect ◽

Type I Error ◽

Bayesian Hierarchical Model ◽

Error Rates ◽

Type I ◽

Bayesian Hierarchical ◽

Type I Error Rates ◽

Information Borrowing ◽

Basket Trials

Background: The basket trial evaluates the treatment effect of a targeted therapy in patients with the same genetic or molecular aberration, regardless of their cancer types. Bayesian hierarchical modeling has been proposed to adaptively borrow information across cancer types to improve the statistical power of basket trials. Although conceptually attractive, research has shown that Bayesian hierarchical models cannot appropriately determine the degree of information borrowing and may lead to substantially inflated type I error rates. Methods: We propose a novel calibrated Bayesian hierarchical model approach to evaluate the treatment effect in basket trials. In our approach, the shrinkage parameter that controls information borrowing is not regarded as an unknown parameter. Instead, it is defined as a function of a similarity measure of the treatment effect across tumor subgroups. The key is that the function is calibrated using simulation such that information is strongly borrowed across subgroups if their treatment effects are similar and barely borrowed if the treatment effects are heterogeneous. Results: The simulation study shows that our method has substantially better controlled type I error rates than the Bayesian hierarchical model. In some scenarios, for example, when the true response rate is between the null and alternative, the type I error rate of the proposed method can be inflated from 10% up to 20%, but is still better than that of the Bayesian hierarchical model. Limitation: The proposed design assumes a binary endpoint. Extension of the proposed design to ordinal and time-to-event endpoints is worthy of further investigation. Conclusion: The calibrated Bayesian hierarchical model provides a practical approach to design basket trials with more flexibility and better controlled type I error rates than the Bayesian hierarchical model. The software for implementing the proposed design is available at http://odin.mdacc.tmc.edu/~yyuan/index_code.html

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Bayesian Applications in Auditory Research

Journal of Speech Language and Hearing Research ◽

10.1044/2018_jslhr-h-astm-18-0228 ◽

2019 ◽

Vol 62 (3) ◽

pp. 577-586 ◽

Cited By ~ 9

Author(s):

Garnett P. McMillan ◽

John B. Cannon

Keyword(s):

Monte Carlo ◽

Markov Chain ◽

Bayesian Methods ◽

Prior Distribution ◽

Interim Analysis ◽

Iterative Process ◽

Bayes Theorem ◽

Sound Therapy ◽

The Many ◽

Auditory Research

Purpose This article presents a basic exploration of Bayesian inference to inform researchers unfamiliar to this type of analysis of the many advantages this readily available approach provides. Method First, we demonstrate the development of Bayes' theorem, the cornerstone of Bayesian statistics, into an iterative process of updating priors. Working with a few assumptions, including normalcy and conjugacy of prior distribution, we express how one would calculate the posterior distribution using the prior distribution and the likelihood of the parameter. Next, we move to an example in auditory research by considering the effect of sound therapy for reducing the perceived loudness of tinnitus. In this case, as well as most real-world settings, we turn to Markov chain simulations because the assumptions allowing for easy calculations no longer hold. Using Markov chain Monte Carlo methods, we can illustrate several analysis solutions given by a straightforward Bayesian approach. Conclusion Bayesian methods are widely applicable and can help scientists overcome analysis problems, including how to include existing information, run interim analysis, achieve consensus through measurement, and, most importantly, interpret results correctly. Supplemental Material https://doi.org/10.23641/asha.7822592

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