Related papers: A multi-arm multi-stage design for trials with all…
Multi-arm multi-stage (MAMS) trials have gained popularity, due to their improved efficiency in evaluating multiple treatments. A traditional MAMS trial often decreases the expected sample size of the trial compared to just running a…
There is growing interest in platform trials that allow for adding of new treatment arms as the trial progresses as well as being able to stop treatments part way through the trial for either lack of benefit/futility or for superiority. In…
There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed…
Multi-Arm, Multi-Stage (MAMS) clinical trial designs allow for multiple therapies to be compared across a spectrum of clinical trial phases. MAMS designs can be categorized into several overarching design groups, including adaptive designs…
Multi-Arm Multi-Stage (MAMS) platform trials are an efficient tool for the comparison of several treatments. Suppose we wish to add a treatment to a trial already in progress, to access the benefits of a MAMS design. How should this be…
Background: Experimental treatments pass through various stages of development. If a treatment passes through early phase experiments, the investigators may want to assess it in a late phase randomised controlled trial. An efficient way to…
Primarily motivated by the drug development process, several publications have now presented methodology for the design of multi-arm multi-stage experiments with normally distributed outcome variables of known variance. Here, we extend…
Numerous publications have now addressed the principles of designing, analyzing, and reporting the results of, stepped-wedge cluster randomized trials. In contrast, there is little research available pertaining to the design and analysis of…
The standard paradigm for confirmatory clinical trials is to compare experimental treatments with a control, for example the standard of care or a placebo. However, it is not always the case that a suitable control exists. Efficient…
Multi-arm multi-stage trial designs can bring notable gains in efficiency to the drug development process. However, for normally distributed endpoints, the determination of a design typically depends on the assumption that the patient…
When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…
Platform trials offer a framework to study multiple interventions in a single trial with the opportunity of opening and closing arms. The use of a common control in platform trials can increase efficiency as compared to individual control…
Platform trials are a more efficient way of testing multiple treatments compared to running separate trials. In this paper we consider platform trials where, if a treatment is found to be superior to the control, it will become the new…
In small sample studies with binary outcome data, use of a normal approximation for hypothesis testing can lead to substantial inflation of the type-I error-rate. Consequently, exact statistical methods are necessitated, and accordingly,…
We propose a multi-metric flexible Bayesian framework to support efficient interim decision-making in multi-arm multi-stage phase II clinical trials. Multi-arm multi-stage phase II studies increase the efficiency of drug development, but…
In recent years new cancer treatments improved survival in multiple histologies. Some of these therapeutics, and in particular treatment combinations, are often associated with severe treatment-related adverse events (AEs). It is therefore…
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…
Due to ethical and economical reasons, sequential single-arm trial designs are used for assessing the therapeutic efficacy of new treatments in phase II trials. Simon's 2-stage design and Lan-DeMets' $\alpha$-spending function method with…
Crossover designs are an extremely useful tool to investigators, whilst group sequential methods have proven highly proficient at improving the efficiency of parallel group trials. Yet, group sequential methods and crossover designs have…
A multi-arm multi-stage trial is a multi-arm trial which includes interim analyses - analysing the data at certain specified points, generally discontinuing treatments which are concluded to not work and proceeding with the remainder. It is…