Related papers: A Bayesian Optimal Phase II Design for Randomized …
Immunotherapies have revolutionized cancer treatment. Unlike chemotherapies, immune agents often take longer time to show benefit, and the complex and unique mechanism of action of these agents renders the use of multiple endpoints more…
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…
The Bayesian Optimal Phase II (BOP2) framework is a flexible trial design that can naturally facilitate complex adaptations due to its Bayesian setting. BOP2 uses equal randomisation and equally placed interim analyses in its design, but it…
The conventional phase II trial design paradigm is to make the go/no-go decision based on the hypothesis testing framework. Statistical significance itself alone, however, may not be sufficient to establish that the drug is clinically…
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 use of drug combinations in clinical trials is increasingly common during the last years since a more favorable therapeutic response may be obtained by combining drugs. In phase I clinical trials, most of the existing methodology…
Immunotherapies and targeted therapies have gained popularity due to their promising therapeutic effects across multiple treatment areas. The focus of early phase dose-finding clinical trials has shifted from finding the maximum tolerated…
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…
Many phase II clinical trials have used survival outcomes as the primary endpoints in recent decades. Suppose the radiotherapy is evaluated in a phase II trial using survival outcomes. In that case, the competing risk issue often arises…
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…
In oncology, phase II or multiple expansion cohort trials are crucial for clinical development plans. This is because they aid in identifying potent agents with sufficient activity to continue development and confirm the proof of concept.…
It is crucial to design Phase II cancer clinical trials that balance the efficiency of treatment selection with clinical practicality. Sargent and Goldberg proposed a frequentist design that allow decision-making even when the primary…
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…
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…
Clinical trials with time-to-event endpoints, such as overall survival (OS) or progression-free survival (PFS), are fundamental for evaluating new treatments, particularly in immuno-oncology. However, modern therapies, such as…
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…
An assurance calculation is a Bayesian alternative to a power calculation. One may be performed to aid the planning of a clinical trial, specifically setting the sample size or to support decisions about whether or not to perform a study.…
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,…
In this paper we consider two-stage adaptive dose-response study designs, where the study design is changed at an interim analysis based on the information collected so far. In a simulation study, two approaches will be compared for these…
Interval designs are a class of phase I trial designs for which the decision of dose assignment is determined by comparing the observed toxicity rate at the current dose with a prespecified (toxicity tolerance) interval. If the observed…