Related papers: Improving Maximum Tolerated Dose Selection in Mode…
Uncertainty of decisions in safety-critical engineering applications can be estimated on the basis of the Bayesian Markov Chain Monte Carlo (MCMC) technique of averaging over decision models. The use of decision tree (DT) models assists…
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…
Exploratory cancer drug studies test multiple tumor cell lines against multiple candidate drugs. The goal in each paired (cell line, drug) experiment is to map out the dose-response curve of the cell line as the dose level of the drug…
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,…
The issue of determining not only an adequate dose but also a dosing frequency of a drug arises frequently in Phase II clinical trials. This results in the comparison of models which have some parameters in common. Planning such studies…
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…
Purpose: Various dose calculation algorithms are available for radiation therapy for cancer patients. However, these algorithms are faced with the tradeoff between efficiency and accuracy. The fast algorithms are generally less accurate,…
We propose to develop deep learning models that can predict Pareto optimal dose distributions by using any given set of beam angles, along with patient anatomy, as input to train the deep neural networks. We implement and compare two deep…
Personalized cancer treatments based on the molecular profile of a patient's tumor are an emerging and exciting class of treatments in oncology. As genomic tumor profiling is becoming more common, targeted treatments to specific molecular…
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…
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…
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,…
Most conventional risk analysis methods rely on a single best estimate of exposure per person which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the…
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…
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…
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…
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 mixed-logit model is a flexible tool in transportation choice analysis, which provides valuable insights into inter and intra-individual behavioural heterogeneity. However, applications of mixed-logit models are limited by the high…
Traditional phase I dose finding cancer clinical trial designs aim to determine the maximum tolerated dose (MTD) of the investigational cytotoxic agent based on a single toxicity outcome, assuming a monotone dose-response relationship.…
Conventionally, a first-in-human phase I trial in healthy volunteers aims to confirm the safety of a drug in humans. In such situations, volunteers should not suffer from any safety issues and simple algorithm-based dose-escalation schemes…