Incorporating Surrogate Information for Adaptive Subgroup Enrichment Design with Sample Size Re-estimation

11/03/2021
by   Liwen Wu, et al.
0

Adaptive subgroup enrichment design is an efficient design framework that allows accelerated development for investigational treatments while also having flexibility in population selection within the course of the trial. The adaptive decision at the interim analysis is commonly made based on the conditional probability of trial success. However, one of the critical challenges for such adaptive designs is immature data for interim decisions, particularly in the targeted subgroup with a limited sample size at the first stage of the trial. In this paper, we improve the interim decision making by incorporating information from surrogate endpoints when estimating conditional power at the interim analysis, by predicting the primary treatment effect based on the observed surrogate endpoint and prior knowledge or historical data about the relationship between endpoints. Modified conditional power is developed for both selecting the patient population to be enrolled after the interim analysis and sample size re-estimation. In the simulation study, our proposed design shows a higher chance to make desirable interim decisions and achieves higher overall power, while controlling the overall type I error. This performance is robust over drift of prior knowledge from the true relationship between two endpoints. We also demonstrate the application of our proposed design in two case studies in oncology and vaccine trials.

READ FULL TEXT

page 34

page 37

page 38

page 39

page 40

10/13/2020

Conditional Power and Friends: The Why and How of (Un)planned, Unblinded Sample Size Recalculations in Confirmatory Trials

Adapting the final sample size of a trial to the evidence accruing durin...
12/29/2020

Sample Size Re-estimation Design in Phase II Dose Finding Study with Multiple Dose Groups: Frequentist and Bayesian Methods

Unblinded sample size re-estimation (SSR) is often planned in a clinical...
08/05/2021

Improving the Power of Economic Experiments Using Adaptive Designs

An important issue for many economic experiments is how the experimenter...
09/02/2020

A pragmatic adaptive enrichment design for selecting the right target population for cancer immunotherapies

One of the challenges in the design of confirmatory trials is to deal wi...
04/17/2020

Multiplicity for a Group Sequential Trial with Biomarker Subpopulations

Biomarker subpopulations have become increasingly important for drug dev...
10/04/2018

ASIED: A Bayesian Adaptive Subgroup-Identification Enrichment Design

Developing targeted therapies based on patients' baseline characteristic...