Borrowing of information across patient subgroups in a basket trial based on distributional discrepancy

Basket trials have emerged as a new class of efficient approaches in oncology to evaluate a new treatment in several patient subgroups simultaneously. In this article, we extend the key ideas to disease areas outside of oncology, developing a robust Bayesian methodology for randomized, placebo-controlled basket trials with a continuous endpoint to enable borrowing of information across subtrials with similar treatment effects. After adjusting for covariates, information from a complementary subtrial can be represented into a commensurate prior for the parameter that underpins the subtrial under consideration. We propose using distributional discrepancy to characterize the commensurability between subtrials for appropriate borrowing of information through a spike-and-slab prior, which is placed on the prior precision factor. When the basket trial has at least three subtrials, commensurate priors for point-to-point borrowing are combined into a marginal predictive prior, according to the weights transformed from the pairwise discrepancy measures. In this way, only information from subtrial(s) with the most commensurate treatment effect is leveraged. The marginal predictive prior is updated to a robust posterior by the contemporary subtrial data to inform decision making. Operating characteristics of the proposed methodology are evaluated through simulations motivated by a real basket trial in chronic diseases. The proposed methodology has advantages compared to other selected Bayesian analysis models, for (i) identifying the most commensurate source of information and (ii) gauging the degree of borrowing from specific subtrials. Numerical results also suggest that our methodology can improve the precision of estimates and, potentially, the statistical power for hypothesis testing.

Automated summary

Basket trials have emerged as a new efficient approach in oncology for evaluating new treatments across multiple patient subgroups simultaneously. This article expands on the key ideas and applies them to disease areas beyond oncology. It introduces a robust Bayesian methodology for randomized, placebo-controlled basket trials with a continuous endpoint, allowing for borrowing of information across subtrials with similar treatment effects. The proposed methodology is evaluated through simulations and demonstrates advantages over other Bayesian analysis models in terms of identifying the most commensurate source of information and gauging the degree of borrowing from specific subtrials. Numerical results indicate that the methodology can improve the precision of estimates and potentially enhance the statistical power for hypothesis testing.