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We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly…

The determination of the sample size required by a crossover trial typically depends on the specification of one or more variance components. Uncertainty about the value of these parameters at the design stage means that there is often a…

Aims: Combinations of treatments can offer additional benefit over the treatments individually. However, trials of these combinations are lower priority than the development of novel therapies, which can restrict funding, timelines and…

An accurately identified maximum tolerated dose (MTD) serves as the cornerstone of successful subsequent phases in oncology drug development. Bayesian logistic regression model (BLRM) is a popular and versatile model-based dose-finding…

Drug dosing is an important application of AI, which can be formulated as a Reinforcement Learning (RL) problem. In this paper, we identify two major challenges of using RL for drug dosing: delayed and prolonged effects of administering…

Causal inference problems often involve continuous treatments, such as dose, duration, or frequency. However, identifying and estimating standard dose-response estimands requires that everyone has some chance of receiving any level of the…

Clinical trials in specific indications require the administration of rescue medication in case a patient does not sufficiently respond to investigational treatment. The application of additional treatment on an as needed basis causes…

In Oncology, trials evaluating drug combinations are becoming more common. While combination therapies bring the potential for greater efficacy, they also create unique challenges for ensuring drug safety. In Phase-I dose escalation trials…

Longitudinal targeted maximum likelihood estimation (LTMLE) has very rarely been used to estimate dynamic treatment effects in the context of time-dependent confounding affected by prior treatment when faced with long follow-up times,…

We propose a dynamic allocation procedure that increases power and efficiency when measuring an average treatment effect in sequential randomized trials. Subjects arrive iteratively and are either randomized or paired via a matching…

A bioequivalence study is a type of clinical trial designed to compare the biological equivalence of two different formulations of a drug. Such studies are typically conducted in controlled clinical settings with human subjects, who are…

When choosing estimands and estimators in randomized clinical trials, caution is warranted as intercurrent events, such as - due to patients who switch treatment after disease progression, are often extreme. Statistical analyses may then…

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…

Dose optimization is a hallmark of Project Optimus for oncology drug development. The number of doses to include in a dose optimization study depends on the totality of evidence, which is often unclear in early-phase development. With equal…

In this article, we propose a phase I-II design in two stages for the combination of molecularly targeted therapies. The design is motivated by a published case study that combines a MEK and a PIK3CA inhibitors; a setting in which higher…

Background: Incidence of adverse outcome events rises as patients with advanced illness approach end-of-life. Exposures that tend to occur near end-of-life, e.g., use of wheelchair, oxygen therapy and palliative care, may therefore be found…

Recently there has been much work on early phase cancer designs that incorporate both toxicity and efficacy data, called Phase I-II designs because they combine elements of both phases. However, they do not explicitly address the Phase II…

Warfarin is a widely used anticoagulant, and has a narrow therapeutic range. Dosing of warfarin should be individualized, since slight overdosing or underdosing can have catastrophic or even fatal consequences. Despite much research on…

Uplift modeling is an emerging machine learning approach for estimating the treatment effect at an individual or subgroup level. It can be used for optimizing the performance of interventions such as marketing campaigns and product designs.…

For the analysis of a time-to-event endpoint in a single-arm or randomized clinical trial it is generally perceived that interpretation of a given estimate of the survival function, or the comparison between two groups, hinges on some…