Related papers: Optimal scheduling of interim analyses in group se…
Oncology dose-finding trials are shifting from identifying the maximum tolerated dose (MTD) to determining the optimal biological dose (OBD), driven by the need for efficient methods that consider both toxicity and efficacy. This is…
Mid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of…
Longitudinal cluster randomized trials (L-CRTs) are increasingly used to evaluate the cost-effectiveness of healthcare interventions across multiple assessment periods, yet design methods for powering these trials remain underdeveloped.…
This article develops a method to construct the optimal sequential test for monitoring the changes in the distribution of finite observation sequences with a general dependence structure. This method allows us to prove that different…
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.…
Background: trials to identify the minimal effective treatment duration are needed in different therapeutic areas, including bacterial infections, TB and Hepatitis--C. However, standard non-inferiority designs have several limitations,…
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…
We present a new experimental design procedure that divides a set of experimental units into two groups in order to minimize error in estimating an additive treatment effect. One concern is minimizing error at the experimental design stage…
This manuscript investigates unconditional and conditional-on-stopping maximum likelihood estimators (MLEs), information measures and information loss associated with conditioning in group sequential designs (GSDs). The possibility of early…
The conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase…
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…
Group sequential designs (GSDs) are widely used in confirmatory trials to allow interim monitoring while preserving control of the type I error rate. In the frequentist framework, O'Brien-Fleming-type stopping boundaries dominate practice…
We propose a prognostic stratum matching framework that addresses the deficiencies of Randomized trial data subgroup analysis and transforms ObservAtional Data to be used as if they were randomized, thus paving the road for precision…
The restricted mean survival time (RMST) is the mean survival time in the study population followed up to a specific time point, and is simply the area under the survival curve up to the specific time point. The difference between two RMSTs…
Stepped wedge designs (SWDs) are increasingly used to evaluate longitudinal cluster-level interventions but pose substantial challenges for valid inference. Because crossover times are randomized, intervention effects are intrinsically…
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…
Multidimensional Retiming is one of the most important optimization techniques to improve timing parameters of nested loops. It consists in exploring the iterative and recursive structures of loops to redistribute computation nodes on cycle…
In longitudinal studies, we observe measurements of the same variables at different time points to track the changes in their pattern over time. In such studies, scheduling of the data collection waves (i.e. time of participants' visits) is…
Personalized medicine has gained much popularity recently as a way of providing better healthcare by tailoring treatments to suit individuals. Our research, motivated by the UK INTERVAL blood donation trial, focuses on estimating the…
The US Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection towards identifying the optimal biological dose that offers the best balance between benefit and risk, rather…