A win ratio-based framework to combine multiple clinical endpoints in exploratory basket trials

ABSTRACT

In contemporary exploratory phase of oncology drug development, there has been an increasing interest in evaluating investigational drug or drug combination in multiple tumor indications in a single basket trial to expedite drug development. There has been extensive research on more efficiently borrowing information across tumor indications in early phase drug development including Bayesian hierarchical modeling and the pruning-and-pooling methods. Despite the fact that the Go/No-Go decision for subsequent Phase 2 or Phase 3 trial initiation is almost always a multi-facet consideration, the statistical literature of basket trial design and analysis has largely been limited to a single binary endpoint. In this paper we explore the application of considering clinical priorities of multiple endpoints based on matched win ratio to the basket trial design and analysis. The control arm data will be simulated for each tumor indication based on the corresponding null assumptions that could be heterogeneous across tumor indications. The matched win ratio matching on the tumor indication can be performed for individual tumor indication, pooled data, or the pooled data after pruning depending on whether an individual evaluation or a simple pooling or a pruning-and-pooling method is used. We conduct the simulation studies to evaluate the performance of proposed win ratio-based framework and the results suggest the proposed framework could provide desirable operating characteristics.

KEYWORDS:

• Basket trial
• multiple endpoints
• matched win ratio
• simulation

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/10543406.2023.2187819.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.