Statistical design considerations for trials that study multiple indications

07/07/2020
by   Alexander M. Kaizer, et al.
0

Breakthroughs in cancer biology have defined new research programs emphasizing the development of therapies that target specific pathways in tumor cells. Innovations in clinical trial design have followed with master protocols defined by inclusive eligibility criteria and evaluations of multiple therapies and/or histologies. Consequently, characterization of subpopulation heterogeneity has become central to the formulation and selection of a study design. However, this transition to master protocols has led to challenges in identifying the optimal trial design and proper calibration of hyperparameters. We often evaluate a range of null and alternative scenarios, however there has been little guidance on how to synthesize the potentially disparate recommendations for what may be optimal. This may lead to the selection of suboptimal designs and statistical methods that do not fully accommodate the subpopulation heterogeneity. This article proposes novel optimization criteria for calibrating and evaluating candidate statistical designs of master protocols in the presence of the potential for treatment effect heterogeneity among enrolled patient subpopulations. The framework is applied to demonstrate the statistical properties of conventional study designs when treatments offer heterogeneous benefit as well as identify optimal designs devised to monitor the potential for heterogeneity among patients with differing clinical indications using Bayesian modeling.

READ FULL TEXT

page 7

page 14

page 15

page 22

page 24

page 25

page 26

page 27

research
07/11/2023

Considerations for Master Protocols Using External Controls

There has been an increasing use of master protocols in oncology clinica...
research
01/11/2023

Precision Dose-finding Cancer Clinical Trials in the Setting of Broadened Eligibility

Broadening eligibility criteria in cancer trials has been advocated to r...
research
06/25/2019

Automatic Conversion from Flip-flop to 3-phase Latch-based Designs

Latch-based designs have many benefits over their flip-flop based counte...
research
11/11/2021

Design of porthole aluminium extrusion dies through mathematical formulation

A mathematical approach to solve the porthole die design problem is achi...
research
07/13/2021

The Future will be Different than Today: Model Evaluation Considerations when Developing Translational Clinical Biomarker

Finding translational biomarkers stands center stage of the future of pe...
research
03/22/2018

Learning Eligibility in Clinical Cancer Trials using Deep Neural Networks

Interventional clinical cancer trials are generally too restrictive and ...

Please sign up or login with your details

Forgot password? Click here to reset