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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…

Breakthroughs in cancer biology have defined new research programs emphasizing the development of therapies that target specific pathways in tumor cells. Innovations in clinical trial design have followed with master protocols defined by…

Dual agent dose-finding trials study the effect of a combination of more than one agent, where the objective is to find the Maximum Tolerated Dose Combination (MTC), the combination of doses of the two agents that is associated with a…

This paper proposes a novel criterion for the allocation of patients in Phase~I dose-escalation clinical trials aiming to find the maximum tolerated dose (MTD). Conventionally, using a model-based approach the next patient is allocated to…

Phase I early-phase clinical studies aim at investigating the safety and the underlying dose-toxicity relationship of a drug or combination. While little may still be known about the compound's properties, it is crucial to consider…

This paper introduces a new Phase I design aimed at enhancing the performance of existing methods, including algorithm-based, model-based, and model-assisted designs. The design, developed by integrating the concept of Fisher information,…

A/B testing is critical for modern technological companies to evaluate the effectiveness of newly developed products against standard baselines. This paper studies optimal designs that aim to maximize the amount of information obtained from…

We study the problem of finding the optimal dosage in early stage clinical trials through the multi-armed bandit lens. We advocate the use of the Thompson Sampling principle, a flexible algorithm that can accommodate different types of…

This work considers the problem of personalized dose guidance using Bayesian optimization that learns the optimum drug dose tailored to each individual, thus improving therapeutic outcomes. Safe learning using interior point method ensures…

Background: Phase I trials desire to identify the maximum tolerated dose (MTD) early and proceed quickly to an expansion cohort or phase II trial for efficacy. We propose an early completion method based on multiple dosages to accelerate…

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…

Drug combination trials are increasingly common nowadays in clinical research. However, very few methods have been developed to consider toxicity attributions in the dose escalation process. We are motivated by a trial in which the…

We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding…

We consider design issues for toxicology studies when we have a continuous response and the true mean response is only known to be a member of a class of nested models. This class of non-linear models was proposed by toxicologists who were…

This paper presents a quasi-sequential optimal design framework for toxicology experiments, specifically applied to sea urchin embryos. The authors propose a novel approach combining robust optimal design with adaptive, stage-based testing…

We propose Locally Optimal Restricted Designs (LORDs) for phase I/II dose-finding studies that focus on both efficacy and toxicity outcomes. As an illustrative application, we find various LORDs for a 4-parameter continuation-ratio (CR)…

Significant evidence has become available that emphasizes the importance of personalization in medicine. In fact, it has become a common belief that personalized medicine is the future of medicine. The core of personalized medicine is the…

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…

We consider a modified Ci3+3 (MCi3+3) design for dual-agent dose-finding trials in which both agents are tested on multiple doses. This usually happens when the agents are novel therapies. The MCi3+3 design offers a two-stage or three-stage…

Optimal experimental design approaches are seldom used in pre-clinical drug discovery. Main reasons for this lack of use are that available software tools require relatively high insight in optimal design theory, and that the…