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Dose-escalation trials in oncology drug development still today typically aim to identify 1-size-fits-all dose recommendations, as arbitrary quantiles of the toxicity thresholds evident in patient samples. In the late 1990s efforts to…
Although optimal control theory has been used for the theoretical study of anti-cancerous drugs scheduling optimization, with the aim of reducing the primary tumor volume, the effect on metastases is often ignored. Here, we use a previously…
Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main…
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…
Efforts to develop biomarker-targeted anti-cancer therapies have progressed rapidly in recent years. Six antibodies acting on programmed death ligand 1 or programmed death 1 pathways were approved in 75 cancer indications between 2015 and…
Broadening eligibility criteria in cancer trials has been advocated to represent the true patient population more accurately. While the advantages are clear in terms of generalizability and recruitment, novel dose-finding designs are needed…
We identify three properties of the standard oncology phase I trial design or 3 + 3 design. We show that the standard design implicitly uses isotonic regression to estimate a maximum tolerated dose. We next illustrate the relationship…
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,…
When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…
In single-arm phase II oncology trials, the most popular choice of design is Simon's two-stage design, which allows early stopping at one interim analysis. However, the expected trial sample size can be reduced further by allowing…
We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a…
Chemotherapy is one of the primary modalities of cancer treatment. Chemotherapy drug administration is a complex problem that often requires expensive clinical trials to evaluate potential regimens. One way to alleviate this burden and…
The primary goal of dose allocation in phase I trials is to minimize patient exposure to subtherapeutic or excessively toxic doses, while accurately recommending a phase II dose that is as close as possible to the maximum tolerated dose…
The primary objective of phase I cancer clinical trials is to evaluate the safety of a new experimental treatment and to find the maximum tolerated dose (MTD). We show that the MTD estimation problem can be regarded as a level set…
Phase I dose escalation trials in oncology generally aim to find the maximum tolerated dose (MTD). However, with the advent of molecular targeted therapies and antibody drug conjugates, dose limiting toxicities are less frequently observed,…
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…
We propose a frequentist adaptive phase 2 trial design to evaluate the safety and efficacy of three treatment regimens (doses) compared to placebo for four types of helminth (worm) infections. This trial will be carried out in four…
The primary goal of a two-stage Phase I/II trial is to identify the optimal dose for the following large-scale Phase III trial. Recently, Phase I dose-finding designs have shifted from identifying the maximum tolerated dose (MTD) to the…
The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…
Nonlinear regression models addressing both efficacy and toxicity outcomes are increasingly used in dose-finding trials, such as in pharmaceutical drug development. However, research on related experimental design problems for corresponding…