Related papers: Re-thinking non-inferiority: a practical trial des…
Background. Designing trials to reduce treatment duration is important in several therapeutic areas, including TB and antibiotics. We recently proposed a new randomised trial design to overcome some of the limitations of standard two-arm…
Background. The DURATIONS design has been recently proposed as a practical alternative to a standard two-arm non-inferiority design when the goal is to optimise some continuous aspect of treatment administration, e.g. duration or frequency,…
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…
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…
For indications where only unstable reference treatments are available and use of placebo is ethically justified, three-arm `gold standard' designs with an experimental, reference and placebo arm are recommended for non-inferiority trials.…
We study the design of multi-armed parallel group clinical trials to estimate personalized treatment rules that identify the best treatment for a given patient with given covariates. Assuming that the outcomes in each treatment arm are…
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…
Active-controlled trials with non-inferiority objectives are often used when effective interventions are available, but new options may offer advantages or meet public health needs. In these trials, participants are randomized to an…
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…
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…
Minimizing the number of patients exposed to potentially harmful drugs in early onco logical trials is a major concern during planning. Adaptive designs account for the inherent uncertainty about the true effect size by determining the…
Three-arm `gold-standard' non-inferiority trials are recommended for indications where only unstable reference treatments are available and the use of a placebo group can be justified ethically. For such trials several study designs have…
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 an experimenter has the option of running an adaptive trial, is it admissible to ignore this option and run a non-adaptive trial instead? We provide a negative answer to this question in the best-arm identification problem, where the…
Technological advancements in the field of mobile devices and wearable sensors have helped overcome obstacles in the delivery of care, making it possible to deliver behavioral treatments anytime and anywhere. Increasingly the delivery of…
The use of historical controls offers a valuable alternative when traditional randomized controlled trials are not feasible. However, such approaches may introduce bias due to temporal changes in patient populations, diagnostic criteria,…
Background. Non-inferiority (NI) trials are increasingly used to evaluate new treatments expected to have secondary advantages over standard of care, but similar efficacy on the primary outcome. When designing a NI trial with a binary…
Multi-arm bandits are gaining popularity as they enable real-world sequential decision-making across application areas, including clinical trials, recommender systems, and online decision-making. Consequently, there is an increased desire…
In sequential experiments, subjects become available for the study over a period of time, and covariates are often measured at the time of arrival. We consider the setting where the sample size is fixed but covariate values are unknown…
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…