Design of phase III trials with long-term survival outcomes based on short-term binary results

by   Marta Bofill Roig, et al.

Pathologic complete response (pCR) is a common primary endpoint for a phase II trial or even accelerated approval of neoadjuvant cancer therapy. If granted, a two-arm confirmatory trial is often required to demonstrate the efficacy with a time-to-event outcome such as overall survival. However, the design of a subsequent phase III trial based on prior information on the pCR effect is not straightforward. Aiming at designing such phase III trials with overall survival as primary endpoint using pCR information from previous trials, we consider a mixture model that incorporates both the survival and the binary endpoints. We propose to base the comparison between arms on the difference of the restricted mean survival times, and show how the effect size and sample size for overall survival rely on the probability of the binary response and the survival distribution by response status, both for each treatment arm. Moreover, we provide the sample size calculation under different scenarios and accompany them with an R package where all the computations have been implemented. We evaluate our proposal with a simulation study, and illustrate its application through a neoadjuvant breast cancer trial.



There are no comments yet.


page 9


A general class of two-sample statistics for binary and time-to-event outcomes

We propose a class of two-sample statistics for testing the equality of ...

A Survival Mediation Model with Bayesian Model Averaging

Determining the extent to which a patient is benefiting from cancer ther...

Integrating Phase 2 into Phase 3 based on an Intermediate Endpoint While Accounting for a Cure Proportion

For a trial with primary endpoint overall survival for a molecule with c...

Joint modelling of progression-free and overall survival and computation of correlation measures

In this paper, we derive the joint distribution of progression-free and ...

A multistate model for early decision making in oncology

The development of oncology drugs progresses through multiple phases, wh...

Estimating the Distribution of Ratio of Paired Event Times in Phase II Oncology Trials

With the rapid development of new anti-cancer agents which are cytostati...

Bayesian Persuasion in Sequential Trials

We consider a Bayesian persuasion or information design problem where th...
This week in AI

Get the week's most popular data science and artificial intelligence research sent straight to your inbox every Saturday.