# DAE

## Seminar

### Recent developments in adaptive clinical trials to account for individual and collective ethics

Seminar Room 1, Newton Institute

#### Abstract

Most Phase III clinical trials are carried out in order to compare different drugs or therapies. The aim may be to estimate some treatment effects separately or, more commonly, to estimate or test their differences. The ethical concern of assigning treatments to patients so as to care for each of them individually often conflicts with the demands for rigorous experimentation on one hand, and randomization on the other. Recently, there has been a growing statistical interest in sequential procedures for treatment comparison which at each stage use the available information with the ethical aim of skewing allocations towards the best treatment. In two recent papers ([1], [2]) the present authors have approached the problem via the optimization of a compromise criterion, obtained by taking a weighted average of a design optimality measure and a measure of the subjects' risk. The relative weights in the compound criterion have been allowed to depend on the true state of nature, since it is reasonable to suppose that the more the effects of the treatments differ, the more important for the patients are the chances of receiving the best treatment.The purpose of this presentation is to extend the theoretical results of [1] and [2] and enhance their applicability by means of some numerical examples. We shall first of all find a "target" allocation, namely one that optimizes the above-mentioned compound criterion for different response models, also taking into account observable categorical covariates. Since the target does in general depend on the unknown parameters, the implementation of adaptive randomization methods to make the experiment converge to the desired target is illustrated. For simplicity here we consider the most common case of just two treatments.

References

- 1. A. Baldi Antognini, A. Giovagnoli (2010) "Compound Optimal Allocation for Individual and Collective Ethics in Binary Clinical Trials." Biometrika 97(4), 935 - 946
- 2. A. Baldi Antognini, M. Zagoraiou (2010) "Covariate adjusted designs for combining efficiency, ethics and randomness in normal response trials", in mODa 9 - Advances in Model Oriented Design and Analysis (A. Giovagnoli, A. Atkinson, B. Torsney eds, C. May coed.), HEIDELBERG: Physica-Verlag, Springer (GERMANY), 17-24, ISBN: 978-3-7908-2409-4

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