相关论文: A Bayesian adaptive design for dual-agent phase I-…

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…

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…

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 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…

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…

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…

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…

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…

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…

Project Optimus, an initiative by the FDA's Oncology Center of Excellence, seeks to reform the dose-optimization and dose-selection paradigm in oncology. We propose a dose-optimization design that considers plateau efficacy profiles,…

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…

Identification of optimal dose combinations in early phase dose-finding trials is challenging, due to the trade-off between precisely estimating the many parameters required to flexibly model the possibly non-monotonic dose-response…

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…

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…

Recently, the strategy for dose optimization in oncology has shifted to conduct Phase 2 randomized controlled trials with multiple doses. Optimal biologic dose selection from Phase 1 trial data to determine candidate doses for Phase 2…

Phase I dose-escalation trials must be guided by a safety model in order to avoid exposing patients to unacceptably high risk of toxicities. Traditionally, these trials are based on one type of schedule. In more recent practice, however,…

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…

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…

Phase 1-2 designs provide a methodological advance over phase 1 designs for dose finding by using both clinical response and toxicity. A phase 1-2 trial still may fail to select a truly optimal dose. because early response is not a perfect…

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…