Related papers: BOIN Designs for Dose Escalation With Selected Dos…
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…
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…
We consider a Bayesian framework based on "probability of decision" for dose-finding trial designs. The proposed PoD-BIN design evaluates the posterior predictive probabilities of up-and-down decisions. In PoD-BIN, multiple grades of…
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…
In Oncology, trials evaluating drug combinations are becoming more common. While combination therapies bring the potential for greater efficacy, they also create unique challenges for ensuring drug safety. In Phase-I dose escalation trials…
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…
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…
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…
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…
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…
We propose a rule-based statistical design for combination dose-finding trials with two agents. The Ci3+3 design is an extension of the i3+3 design with simple decision rules comparing the observed toxicity rates and equivalence intervals…
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…
It is increasingly common for therapies in oncology to be given in combination. In some cases, patients can benefit from the interaction between two drugs, although often at the risk of higher toxicity. A large number of designs to conduct…
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…
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…
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…
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 landscape of dose-finding designs for phase I clinical trials is rapidly shifting in the recent years, noticeably marked by the emergence of interval-based designs. We categorize them as the iDesigns and the IB-Designs. The iDesigns are…
The traditional more-is-better dose selection paradigm, developed based on cytotoxic chemotherapeutics, is often problematic When applied to the development of novel molecularly targeted agents (e.g., kinase inhibitors, monoclonal…
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…