Related papers: Point estimation for adaptive trial designs I: a m…
In adaptive clinical trials, the conventional end-of-trial point estimate of a treatment effect is prone to bias, that is, a systematic tendency to deviate from its true value. As stated in recent FDA guidance on adaptive designs, it is…
Regulatory guidance notes the need for caution in the interpretation of confidence intervals (CIs) constructed during and after an adaptive clinical trial. Conventional CIs of the treatment effects are prone to undercoverage (as well as…
Adaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical and efficient. These benefits are achieved while preserving the integrity and validity of the…
In adaptive clinical trials, the conventional confidence interval (CI) for a treatment effect is prone to undesirable properties such as undercoverage and potential inconsistency with the final hypothesis testing decision. Accordingly, as…
Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants, use resources efficiently and allow clinically meaningful conclusions to be drawn. Adaptive…
Clinical trials are an instrument for making informed decisions based on evidence from well-designed experiments. Here we consider adaptive designs mainly from the perspective of multi-arm Phase II clinical trials, in which one or more…
For randomized clinical trials where a single, primary, binary endpoint would require unfeasibly large sample sizes, composite endpoints are widely chosen as the primary endpoint. Despite being commonly used, composite endpoints entail…
The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…
Adaptive designs are commonly used in clinical and drug development studies for optimum utilization of available resources. In this article, we consider the problem of estimating the effect of the selected (better) treatment using a…
From scientific experiments to online A/B testing, the previously observed data often affects how future experiments are performed, which in turn affects which data will be collected. Such adaptivity introduces complex correlations between…
Given n experiment subjects with potentially heterogeneous covariates and two possible treatments, namely active treatment and control, this paper addresses the fundamental question of determining the optimal accuracy in estimating the…
An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…
Background: Advanced adaptive randomised clinical trials are increasingly used. Compared to their conventional counterparts, their flexibility may make them more efficient, increase the probability of obtaining conclusive results without…
Clinical trials with time-to-event endpoints, such as overall survival (OS) or progression-free survival (PFS), are fundamental for evaluating new treatments, particularly in immuno-oncology. However, modern therapies, such as…
A new approach to adaptive design of clinical trials is proposed in a general multiparameter exponential family setting, based on generalized likelihood ratio statistics and optimal sequential testing theory. These designs are easy to…
Bayesian adaptive designs have gained popularity in all phases of clinical trials with numerous new developments in the past few decades. During the COVID-19 pandemic, the need to establish evidence for the effectiveness of vaccines,…
Attrition is a common and potentially important threat to internal validity in treatment effect studies. We extend the changes-in-changes approach to identify the average treatment effect for respondents and the entire study population in…
Adaptive experiment designs can dramatically improve statistical efficiency in randomized trials, but they also complicate statistical inference. For example, it is now well known that the sample mean is biased in adaptive trials.…
Adaptive designs have been proposed for clinical trials in which the nuisance parameters or alternative of interest are unknown or likely to be misspecified before the trial. Whereas most previous works on adaptive designs and mid-course…
An adaptive design adjusts dynamically as information is accrued and a consequence of applying an adaptive design is the potential for inducing small-sample bias in estimates. In psychometrics and psychophysics, a common class of studies…