Related papers: Group Sequential Crossover Trial Designs with Stro…
Group sequential design (GSD) is widely used in clinical trials in which correlated tests of multiple hypotheses are used. Multiple primary objectives resulting in tests with known correlations include evaluating 1) multiple experimental…
Group sequential designs drive innovation in clinical, industrial, and corporate settings. Early stopping for failure in sequential designs conserves experimental resources, whereas early stopping for success accelerates access to improved…
Due to the high cost and high failure rate of Phase III trials, seamless Phase II/III designs are more and more popular to trial efficiency. A potential attraction of Phase II/III design is to allow a randomized proof-of-concept stage prior…
In a group sequential clinical trial, accumulated data are analysed at numerous time-points in order to allow early decisions about a hypothesis of interest. These designs have historically been recommended for their ethical, administrative…
A group sequential clinical trial design can be an attractive option when planning a pivotal trial as this approach has the ability to stop the trial early for success, whilst also being well accepted from a regulatory review perspective.…
Recently, methodology was presented to facilitate the incorporation of interim analyses in stepped-wedge (SW) cluster randomised trials (CRTs). Here, we extend this previous discussion. We detail how the stopping boundaries, allocation…
Test procedures for multiple hypotheses in a group sequential clinical trial that control the family-wise error rate are considered. Several graphical group sequential tests suggested in the literature, which are special cases of…
Group sequential designs in clinical trials allow for interim efficacy and futility monitoring. Adjustment for baseline covariates can increase power and precision of estimated effects. However, inconsistently applying covariate adjustment…
Biomarker subpopulations have become increasingly important for drug development in targeted therapies. The use of biomarkers has the potential to facilitate more effective outcomes by guiding patient selection appropriately, thus enhancing…
This paper deals exclusively with crossover designs for the purpose of comparing t test treatments with a control treatment when the number of periods is no larger than t+1. Among other results it specifies sufficient conditions for a…
The win ratio is increasingly used in randomized trials due to its intuitive clinical interpretation, ability to incorporate the relative importance of composite endpoints, and its capacity for combining different types of outcomes (e.g.…
We describe group sequential tests which efficiently incorporate information from multiple endpoints allowing for early stopping at pre-planned interim analyses. We formulate a testing procedure where several outcomes are examined, and…
Crossover designs randomly assign each unit to receive a sequence of treatments. By comparing outcomes within the same unit, these designs can effectively eliminate between-unit variation and facilitate the identification of both…
This article discusses D-optimal Bayesian crossover designs for generalized linear models. Crossover trials with t treatments and p periods, for $t <= p$, are considered. The designs proposed in this paper minimize the log determinant of…
The primary analysis in two-arm clinical trials usually involves inference on a scalar treatment effect parameter; e.g., depending on the outcome, the difference of treatment-specific means, risk difference, risk ratio, or odds ratio. Most…
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…
In clinical trials, there is potential to improve precision and reduce the required sample size by appropriately adjusting for baseline variables in the statistical analysis. This is called covariate adjustment. Despite recommendations by…
Multi-arm multi-stage (MAMS) trials have gained popularity to enhance the efficiency of clinical trials, potentially reducing both duration and costs. This paper focuses on designing MAMS trials where no control treatment exists. This can…
Count data and recurrent events in clinical trials, such as the number of lesions in magnetic resonance imaging in multiple sclerosis, the number of relapses in multiple sclerosis, the number of hospitalizations in heart failure, and the…
It has been argued for many years that models used to analyze data from crossover designs are not appropriate when simple carryover effects are assumed. Furthermore, a statistical model that could estimate complex carry-over effects in…