Related papers: Design and Sample Size Determination for Multiple-…
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…
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…
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…
Biomarker-guided designs are increasingly used to evaluate personalized treatments based on patients' biomarker status in Phase II and III clinical trials. With adaptive enrichment, these designs can improve the efficiency of evaluating the…
Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing…
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…
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…
In the development of new cancer treatment, an essential step is to determine the maximum tolerated dose (MTD) via phase I clinical trials. Generally speaking, phase I trial designs can be classified as either model-based or algorithm-based…
Phase I clinical trials are designed to test the safety (non-toxicity) of drugs and find the maximum tolerated dose (MTD). This task becomes significantly more challenging when multiple-drug dose-combinations (DC) are involved, due to the…
Purpose: The early identification of maximum tolerated dose (MTD) in phase I trial leads to faster progression to a phase II trial or an expansion cohort to confirm efficacy. Methods: We propose a novel adaptive design for identifying MTD…
In clinical trials, response-adaptive randomization (RAR) has the appealing ability to assign more subjects to better-performing treatments based on interim results. The traditional RAR strategy alters the randomization ratio on a…
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…
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…
Nowadays, more and more clinical trials choose combinational agents as the intervention to achieve better therapeutic responses. However, dose-finding for combinational agents is much more complicated than single agent as the full order of…
A two-stage adaptive optimal design is an attractive option for increasing the efficiency of clinical trials. In these designs, based on interim data, the locally optimal dose is chosen for further exploration, which induces dependencies…
Phase I-II cancer clinical trial designs are intended to accelerate drug development. In cases where efficacy cannot be ascertained in a short period of time, it is common to divide the study in two stages: i) a first stage in which dose is…
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…
Dose-finding clinical trials in oncology aim to determine the maximum tolerated dose (MTD) of a new drug, generally defined by the proportion of patients with short-term dose-limiting toxicities (DLTs). Model-based approaches for such phase…
In response to the U.S.\ Food and Drug Administration's (FDA) Project Optimus, a paradigm shift is underway in the design of early-phase oncology trials. To accelerate drug development, seamless Phase I/II designs have gained increasing…
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…