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The US Food and Drug Administration (FDA) launched Project Optimus and issued guidance to reform dose-finding and selection trials, shifting the paradigm from identifying the maximum tolerable dose (MTD) to determining the optimal…
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…
Adaptive designs have been proposed for clinical trials in which the nuisance parameters or alternative of interest are unknown or likely to be misspecified before the trial. Whereas most previous works on adaptive designs and mid-course…
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…
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…
For many years Phase I and Phase II clinical trials were conducted separately, but there was a recent shift to combine these Phases. While a variety of Phase~I/II model-based designs for cytotoxic agents were proposed in the literature,…
Early phase, personalized dose-finding trials for combination therapies seek to identify patient-specific optimal biological dose (OBD) combinations, which are defined as safe dose combinations which maximize therapeutic benefit for a…
We consider the optimal design problem for identifying effective dose combinations within drug combination studies where the effect of the combination of two drugs is investigated. Drug combination studies are becoming increasingly…
Group sequential designs (GSDs) are well established and the most commonly used adaptive design in confirmatory clinical trials with interim analyses. However, they remain underutilised, and their implementation involves unique theoretical…
Dose optimization in oncology clinical trials has shifted from seeking the maximum tolerated dose to identifying the Optimal Biological Dose (OBD) that balances therapeutic benefits and risks across multiple clinical attributes. Existing…
The purpose of a phase I dose-finding clinical trial is to investigate the toxicity profiles of various doses for a new drug and identify the maximum tolerated dose. Over the past three decades, various dose-finding designs have been…
A multicompartment mathematical model is presented with the goal of studying the role of dose-dense protocols in the context of combination cancer chemotherapy. Dose-dense protocols aim at reducing the period between courses of chemotherapy…
Model-assisted interval designs such as the Keyboard design are transparent and easy to implement in phase I oncology trials. However, interim decisions based solely on data from the current dose may overlook informative signals from…
We propose to use Bayesian optimization (BO) to improve the efficiency of the design selection process in clinical trials. BO is a method to optimize expensive black-box functions, by using a regression as a surrogate to guide the search.…
An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…
Purpose: During discussions at the Data Science Roundtable meeting in Japan, there were instances where the adoption of the BOIN design was declined, attributed to the extension of study duration and increased sample size in comparison to…
Traditionally, the major objective in phase I trials is to identify a working-dose for subsequent studies, whereas the major endpoint in phase II and III trials is treatment efficacy. The dose sought is typically referred to as the maximum…
Data collection costs can vary widely across variables in data science tasks. Two-phase designs can be employed to save data collection costs. This paper considers the two-phase studies where inexpensive variables are collected for all…
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…
Decision-making in personalized medicine such as cancer therapy or critical care must often make choices for dosage combinations, i.e., multiple continuous treatments. Existing work for this task has modeled the effect of multiple…