Utility-based optimization of Fujikawa's basket trial design -- Pre-specified protocol of a comparison study

TL;DR

This paper presents a pre-specified protocol for a comparison study that uses utility functions and numerical optimization to improve basket trial designs by balancing power and type-I error inflation.

Contribution

It introduces a structured protocol for optimizing basket trial design parameters using utility-based methods and simulation, which is a novel approach in this context.

Findings

Protocol for utility-based optimization of basket trials

Simulation framework for comparing design strategies

Pre-specified steps following ADEMP scheme

Abstract

Basket trial designs are a type of master protocol in which the same therapy is tested in several strata of the patient cohort. Many basket trial designs implement borrowing mechanisms. These allow sharing information between similar strata with the goal of increasing power in responsive strata while at the same time constraining type-I error inflation to a bearable threshold. These borrowing mechanisms can be tuned using numerical tuning parameters. The optimal choice of these tuning parameters is subject to research. In a comparison study using simulations and numerical calculations, we are planning to investigate the use of utility functions for quantifying the compromise between power and type-I error inflation and the use of numerical optimization algorithms for optimizing these functions. The present document is the protocol of this comparison study, defining each step of the study in accordance with the ADEMP scheme for pre-specification of simulation studies.