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In precision oncology, integrating multiple cancer patient subgroups into a single master protocol allows for the simultaneous assessment of treatment effects in these subgroups and promotes the sharing of information between them, ultimately reducing sample sizes and costs and enhancing scientific validity. However, the safety and efficacy of these therapies may vary across different subgroups, resulting in heterogeneous outcomes. Therefore, identifying subgroup-specific optimal doses in early-phase clinical trials is crucial for the development of future trials. In this article, we review various innovative Bayesian information-borrowing strategies that aim to determine and optimize subgroup-specific doses. Specifically, we discuss Bayesian hierarchical modeling, Bayesian clustering, Bayesian model averaging or selection, pairwise borrowing, and other relevant approaches. By employing these Bayesian information-borrowing methods, investigators can gain a better understanding of the intricate relationships between dose, toxicity, and efficacy in each subgroup. This increased understanding significantly improves the chances of identifying an optimal dose tailored to each specific subgroup. Furthermore, we present several practical recommendations to guide the design of future early-phase oncology trials involving multiple subgroups when using the Bayesian information-borrowing methods.
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http://dx.doi.org/10.1177/17407745231212193 | DOI Listing |
Biom J
August 2025
Daiichi Sankyo, Inc, Basking Ridge, New Jersey, USA.
In recent years, basket trials, which allow the evaluation of an experimental therapy across multiple tumor types within a single protocol, have gained prominence in early-phase oncology development. Unlike traditional trials, which evaluate each tumor type separately and often face challenges with limited sample sizes, basket trials offer the advantage of borrowing information across various tumor types to enhance statistical power. However, a key challenge in designing basket trials is determining the appropriate extent of information borrowing while maintaining an acceptable type I error rate control.
View Article and Find Full Text PDFBiometrics
April 2025
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
In cancer treatment, the development of combination therapies requires demonstrating the contribution of each individual drug and optimizing the dose during early-phase trials. This necessitates a large sample size, presenting formidable obstacles for drug developers. To address this issue, we propose a 2-stage randomized phase II design that seamlessly integrates combination dose optimization with component contribution assessment.
View Article and Find Full Text PDFBiostatistics
December 2024
MRC Biostatistics Unit, University of Cambridge, East Forvie Building, Robinson Way, Cambridge, Cambridgeshire, CB2 0SR, United Kingdom.
In basket trials a single therapeutic treatment is tested on several patient populations simultaneously, each of which forming a basket, where patients across all baskets on the trial share a common genetic aberration. These trials allow testing of treatments on small groups of patients, however, limited basket sample sizes can result in inadequate precision and power of estimates. It is well known that Bayesian information borrowing models such as the exchangeability-nonexchangeability (EXNEX) model can be implemented to tackle such a problem, drawing on information from one basket when making inference in another.
View Article and Find Full Text PDFJ Comput Biol
June 2025
Institute of Mathematical Sciences, ShanghaiTech University, Shanghai, China.
Imaging genetics aims to uncover the hidden relationship between imaging quantitative traits (QTs) and genetic markers [e.g., single nucleotide polymorphism (SNP)] and brings valuable insights into the pathogenesis of complex diseases, such as cancers and cognitive disorders (e.
View Article and Find Full Text PDFStat Med
June 2025
Takeda Pharmaceuticals, Cambridge, Massachusetts, USA.
Randomized controlled trials (RCTs) are considered the gold standard for evaluating treatment efficacy, but they come with several practical challenges. These include high costs, lengthy timelines, ethical concerns for participants in placebo or control arms, and issues such as patient attrition and non-compliance. Recruiting patients for the control arm can be particularly challenging, especially in therapeutic areas with high unmet medical needs.
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