Adaptive Clinical Trials: Exploiting Sequential Patient Recruitment and Allocation

TL;DR

This paper introduces an adaptive method for clinical trial patient recruitment and allocation that leverages cohort data and heterogeneity to improve learning efficiency and reduce the number of patients needed.

Contribution

It formulates patient allocation as a Markov Decision Process and proposes an approximate algorithm, RCT-KG, for more efficient trial design compared to uniform randomization.

Findings

Significant reduction in error with the new method.

Fewer patients needed to achieve confidence in treatment effectiveness.

Improved learning efficiency through cohort-based adaptive allocation.

Abstract

Randomized Controlled Trials (RCTs) are the gold standard for comparing the effectiveness of a new treatment to the current one (the control). Most RCTs allocate the patients to the treatment group and the control group by uniform randomization. We show that this procedure can be highly sub-optimal (in terms of learning) if -- as is often the case -- patients can be recruited in cohorts (rather than all at once), the effects on each cohort can be observed before recruiting the next cohort, and the effects are heterogeneous across identifiable subgroups of patients. We formulate the patient allocation problem as a finite stage Markov Decision Process in which the objective is to minimize a given weighted combination of type-I and type-II errors. Because finding the exact solution to this Markov Decision Process is computationally intractable, we propose an algorithm -- \textit{Knowledge Gradient for Randomized Controlled Trials} (RCT-KG) -- that yields an approximate solution. We illustrate our algorithm on a synthetic dataset with Bernoulli outcomes and compare it with uniform randomization. For a given size of trial our method achieves significant reduction in error, and to achieve a prescribed level of confidence (in identifying whether the treatment is superior to the control), our method requires many fewer patients. Our approach uses what has been learned from the effects on previous cohorts to recruit patients to subgroups and allocate patients (to treatment/control) within subgroups in a way that promotes more efficient learning.