Bayesian Interim Analysis in Basket Trials
Pub. online: 4 September 2023 Type: Cancer Research Open Access
1 Department of Statistics, University of Connecticut.
3 Department of Biostatistics, Vir Biotechnology.
2 Department of Biostatistics, Vertex Pharmaceuticals.
5 August 2023
5 August 2023
4 September 2023
4 September 2023
Basket trials have captured much attention in oncology research in recent years, as advances in health technology have opened up the possibility of classification of patients at the genomic level. Bayesian methods are particularly prevalent in basket trials as the hierarchical structure is adapted to basket trials to allow for information borrowing. In this article, we extend the Bayesian methods to basket trials with treatment and control arms for continuous endpoints, which are often the cases in clinical trials for rare diseases. To account for the imbalance in the covariates which are potentially strong predictors but not stratified in a randomized trial, our models make adjustments for these covariates, and allow different coefficients across baskets. In addition, comparisons are drawn between two-stage design and one-stage design for the four Bayesian methods. Extensive simulation studies are conducted to examine the empirical performance of all models under consideration. A real data analysis is carried out to further demonstrate the usefulness of the Bayesian methods.
Supplementary materialSupplementary Material
The Supplementary Material includes the models without covariates supplementary results (Section S.1), sensitivity analysis of MFM (Section S.2), derivation of MFM sampling algorithm formula (Section S.3), and testing treatment difference among baskets for CBHM (Section S.4).
Geng, J. and Hu, G. (2020). Mixture of finite mixtures model for basket trial. arXiv preprint arXiv:2011.04135.
Lopez-Chavez, A., Thomas, A., Rajan, A., Raffeld, M., Morrow, B., Kelly, R., Carter, C. A., Guha, U., Killian, K., Lau, C. C. et al. (2015). Molecular profiling and targeted therapy for advanced thoracic malignancies: a biomarker-derived, multiarm, multihistology phase II basket trial. Journal of Clinical Oncology 33(9) 1000.
Oaknin, A., Friedman, C. F., Roman, L. D., D’Souza, A., Brana, I., Bidard, F. -C., Goldman, J., Alvarez, E. A., Boni, V., ElNaggar, A. C. et al. (2020). Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial. Gynecologic oncology 159(1) 150–156.
Patel, S. P., Othus, M., Chae, Y. K., Giles, F. J., Hansel, D. E., Singh, P. P., Fontaine, A., Shah, M. H., Kasi, A., Baghdadi, T. A. et al. (2020). A Phase II Basket Trial of Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine TumorsIpilimumab and Nivolumab in Rare Tumors S1609: Neuroendocrine. Clinical Cancer Research 26(10) 2290–2296.
U. S. Food and Drug Administration (2018). U.S. Food And Drug Administration: Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/developing-targeted-therapies-low-frequency-molecular-subsets-disease.
U. S. Food and Drug Administration (2018). U.S. Food And Drug Administration: Master Protocols: Efficient Clinical Trial Design Strategies To Expedite Development of Oncology Drugs and Biologics. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/master-protocols-efficient-clinical-trial-design-strategies-expedite-development-oncology-drugs-and.
U. S. Food and Drug Administration (2021). E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e9r1-statistical-principles-clinical-trials-addendum-estimands-and-sensitivity-analysis-clinical.
U. S. Food and Drug Administration (2023). Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products. https://www.fda.gov/media/148910/download.
Wen, P. Y., Stein, A., van den Bent, M., De Greve, J., Wick, A., de Vos, F. Y., von Bubnoff, N., van Linde, M. E., Lai, A., Prager, G. W. et al. (2022). Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial. The Lancet Oncology 23(1) 53–64.