Borrowing of information across patient subgroups in a basket trial based on distributional discrepancy
Abstract
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 paper, we extend the key ideas to disease areas outside of oncology, developing a robust Bayesian methodology for randomised, 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 characterise 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…
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