Related papers: A gated group sequential design for seamless Phase…
FDA's Project Optimus initiative for oncology drug development emphasizes selecting a dose that optimizes both efficacy and safety. When an inferentially adaptive Phase 2/3 design with dose selection is implemented to comply with the…
The identification of surrogate markers is motivated by their potential to make decisions sooner about a treatment effect. However, few methods have been developed to actually use a surrogate marker to test for a treatment effect in a…
We tackle the problem of quantifying failure probabilities for expensive deterministic computer experiments with stochastic inputs under a fixed budget. The computational cost of the computer simulation prohibits direct Monte Carlo (MC) and…
Therapeutic antibody candidates often require extensive engineering to improve key functional and developability properties before clinical development. This can be achieved through iterative design, where starting molecules are optimized…
We consider sequential hypothesis testing based on observations which are received in groups of random size. The observations are assumed to be independent both within and between the groups. We assume that the group sizes are independent…
Accurate detection of infected individuals is one of the critical steps in stopping any pandemic. When the underlying infection rate of the disease is low, testing people in groups, instead of testing each individual in the population, can…
Adaptive subgroup enrichment design is an efficient design framework that allows accelerated development for investigational treatments while also having flexibility in population selection within the course of the trial. The adaptive…
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…
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…
The Stepped Wedge Design (SWD) is a form of cluster randomized trial, usually comparing two treatments, which is divided into time periods and sequences, with clusters allocated to sequences. Typically all sequences start with the standard…
Modern clinical trials and cohort studies gather low-cost data on all participants but may have limited resources to assess expensive exposures such as biomarkers or genomic data. When interest lies in associations involving expensive…
We consider a dose-optimization design for first-in-human oncology trial that aims to identify a suitable dose for late-phase drug development. The proposed approach, called the Pharmacometrics-Enabled DOse OPtimization (PEDOOP) design,…
Triple difference designs have become increasingly popular in empirical economics. The advantage of a triple difference design is that, within a treatment group, it allows for another subgroup of the population -- potentially less impacted…
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…
Both cluster randomized trials and quasi-experimental designs are used to evaluate the impact of health and social policies and interventions. Stepped-wedge cluster randomized trials randomize a staggered adoption approach, while recent…
Seamless phase II/III trials have become a cornerstone of modern drug development, offering a means to accelerate evaluation while maintaining statistical rigor. However, most existing inference procedures are model-based, designed…
A common feature of many recent trials evaluating the effects of immunotherapy on survival is that non-proportional hazards can be anticipated at the design stage. This raises the possibility to use a statistical method tailored towards…
The design of multiple experiments is commonly undertaken via suboptimal strategies, such as batch (open-loop) design that omits feedback or greedy (myopic) design that does not account for future effects. This paper introduces new…
Randomized saturation designs are a family of designs which assign a possibly different treatment proportion to each cluster of a population at random. As a result, they generalize the well-known (stratified) completely randomized designs…
For a trial with primary endpoint overall survival for a molecule with curative potential, statistical methods that rely on the proportional hazards assumption may underestimate the power and the time to final analysis. We show how a cure…