On an ethical cum optimal adaptive allocation design

A randomized two stage allocation for continuous response clinical trials

Abstract: A randomized two treatment allocation design, conducted in two stages, is proposed for a class of continuous response trials. Patients are assigned to each treatment in equal numbers in the first stage and p value of a test of equality of treatment effects based on these data is used to determine the assignment probability of second stage patients. Relevant properties of the proposed allocation design are investigated and compared with suitable competitors.

Adaptive Allocation Designs for Normal and Binary Treatment Responses

Abstract: A class of adaptive designs is formulated in two stages for clinical trials to favour the better performing treatment for further allocation in an efficient way. The first stage of the allocation consists in randomizing subjects to each treatment arm with equal probability and performing a test of equality of treatment effects. The resulting p value and the available estimate of a treatment difference measure is used to assign the incoming second stage subjects. Considering binary and normal responses, several exact and asymptotic properties of the proposed allocation are thoroughly examined and compared with the existing allocation designs.

A multi-treatment two stage adaptive allocation for survival outcomes

Abstract: A multi-treatment two stage adaptive allocation design is developed for survival responses. Assuming noninformative random censoring, asymptotic p values of relevant tests of equality of treatment effects are used to derive the assignment probability of incoming second stage subjects. Several ethical and inferential criteria of the design are studied, and are compared with those of an existing competitor. Applicability and performance of the proposed design are also illustrated using a data arising from a real clinical trial.

A two-stage adaptive allocation design for survival outcome with informative censoring

Abstract: An adaptive two-stage allocation design is developed for survival responses subject to independent informative censoring. The asymptotic p value of a score test related to a hypothesis of treatment effectiveness is used to set the assignment probability of the second stage. Several characteristics of the design and the follow-up inference are studied, both numerically and theoretically, and are compared with those of an existing competitor. Applicability of the proposed design is also illustrated through a real data.

Play the Winner Rule and the Controlled Clinical Trial

Abstract: Consider a clinical trial to compare two treatments where response is dichotomous and patients enter the trial sequentially. This paper investigates the conduct of such a trial where the “Play the Winner Rule” (PWR) is used to assign patients to the different therapies. The implementation of the PWR in a clinical trial tends to place more patients on the better treatment. Both theoretical and numerical investigations show that over a wide range of situations this rule leads to near optimum results when used in a two-stage manner. Furthermore, these results are insensitive to optimum sample size requirements.

The Randomized Play-the-Winner Rule in Medical Trials

Abstract: In a sequential medical trial, a simple randomized treatment assignment rule is proposed and analyzed. On the average this rule assigns more patients to the better treatment, and it is applicable to the case where patients have delayed responses to treatments. This new assignment rule is studied for both a fixed sample size and an inverse stopping rule.

Randomization in Clinical Trials: Theory and Practice

Abstract: Preface Randomization and the Clinical Trial Issues in the Design of Clinical Trials Randomization for Balancing Treatment Assignments Balancing on Known Covariates The Effects of Unobserved Covariates Selection Bias Randomization as a Basis for Inference Inference for Stratified, Blocked, and Covariate-Adjusted Analyses Randomization in Practice Response-Adaptive Randomization Inference for Response-Adaptive Rondomization Response-Adaptive Randomization in Practice Some Useful results in Large Sample Theory Large Sample Inference for Complete and Restricted Randomization Large sample Inference for Response-Adaptive Randomization Author Index Subject Index