Related papers: Oncology Dose Finding Using Approximate Bayesian C…
We consider a modified Ci3+3 (MCi3+3) design for dual-agent dose-finding trials in which both agents are tested on multiple doses. This usually happens when the agents are novel therapies. The MCi3+3 design offers a two-stage or three-stage…
Dose optimization in oncology clinical trials has shifted from seeking the maximum tolerated dose to identifying the Optimal Biological Dose (OBD) that balances therapeutic benefits and risks across multiple clinical attributes. Existing…
Approximate Bayesian Computation (ABC) can be viewed as an analytic approximation of an intractable likelihood coupled with an elementary simulation step. Such a view, combined with a suitable instrumental prior distribution permits…
Approximate Bayesian computation (ABC) is a class of Bayesian inference algorithms that targets for problems with intractable or {unavailable} likelihood function. It uses synthetic data drawn from the simulation model to approximate the…
We consider a formal statistical design that allows simultaneous enrollment of a main cohort and a backfill cohort of patients in a dose-finding trial. The goal is to accumulate more information at various doses to facilitate dose…
Accurate dose calculation is vitally important for proton therapy. Pencil beam (PB) model-based dose calculation is fast but inaccurate due to the approximation when dealing with inhomogeneities. Monte Carlo (MC) dose calculation is the…
ABC (approximate Bayesian computation) is a general approach for dealing with models with an intractable likelihood. In this work, we derive ABC algorithms based on QMC (quasi- Monte Carlo) sequences. We show that the resulting ABC…
Designing clinical trials requires evaluating multiple operating characteristics (OCs), such as the likelihood of an early stopping decision, the probability of detecting a treatment effect, and the Type I error rate. In most cases, these…
Dose-finding studies are frequently conducted to evaluate the effect of different doses or concentration levels of a compound on a response of interest. Applications include the investigation of a new medicinal drug, a herbicide or…
This paper is on Bayesian inference for parametric statistical models that are defined by a stochastic simulator which specifies how data is generated. Exact sampling is then possible but evaluating the likelihood function is typically…
Complicated generative models often result in a situation where computing the likelihood of observed data is intractable, while simulating from the conditional density given a parameter value is relatively easy. Approximate Bayesian…
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…
Pharmacodynamic (PD) models are mathematical models of cellular reaction networks that include drug mechanisms of action. These models are useful for studying predictive therapeutic outcomes of novel drug therapies in silico. However, PD…
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…
Approximate Bayesian Computation (ABC) is a powerful method for carrying out Bayesian inference when the likelihood is computationally intractable. However, a drawback of ABC is that it is an approximate method that induces a systematic…
Purpose: The 3+3 design has been shown to be less likely to achieve the objectives of phase I dose-finding trials when compared with more advanced model-based designs. One major criticism of the 3+3 design is that it is based on simple…
The Project Optimus initiative by the FDA's Oncology Center of Excellence is widely viewed as a groundbreaking effort to change the $\textit{status quo}$ of conventional dose-finding strategies in oncology. Unlike in other therapeutic areas…
Drug discovery is a multi-stage process that comprises two costly major steps: pre-clinical research and clinical trials. Among its stages, lead optimization easily consumes more than half of the pre-clinical budget. We propose a combined…
Incorporating historical data or real-world evidence has a great potential to improve the efficiency of phase I clinical trials and to accelerate drug development. For model-based designs, such as the continuous reassessment method (CRM),…
Dose-finding trials for oncology studies are traditionally designed to assess safety in the early stages of drug development. With the rise of molecularly targeted therapies and immuno-oncology compounds, biomarker-driven approaches have…