Related papers: BARD: A seamless two-stage dose optimization desig…
In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and efficacious that maximises some optimality criterion based on safety and efficacy. This is further complicated when…
FDA's Project Optimus initiative for oncology drug development emphasizes selecting a dose that optimizes both efficacy and safety. When an inferentially adaptive Phase 2/3 design with dose selection is implemented to comply with the…
Mobility systems featuring shared vehicles are often unable to serve all potential customers, as the distribution of demand does not coincide with the positions of vehicles at any given time. System operators often choose to reposition…
We propose Locally Optimal Restricted Designs (LORDs) for phase I/II dose-finding studies that focus on both efficacy and toxicity outcomes. As an illustrative application, we find various LORDs for a 4-parameter continuation-ratio (CR)…
In single-arm phase II oncology trials, the most popular choice of design is Simon's two-stage design, which allows early stopping at one interim analysis. However, the expected trial sample size can be reduced further by allowing…
One of the challenges in the design of confirmatory trials is to deal with uncertainties regarding the optimal target population for a novel drug. Adaptive enrichment designs (AED) which allow for a data-driven selection of one or more…
Automated drug dispensing systems (ADDSs) are increasingly in demand in today's pharmacies, primarily driven by the growing ageing population. Recognizing the practical challenges faced by pharmacies implementing ADDSs, this study aims to…
Cohort-based enrollment can slow down dose-finding trials since the outcomes of the previous cohort must be fully evaluated before the next cohort can be enrolled. This results in frequent suspension of patient enrollment. The issue is…
Spatiotemporal fractionation schemes, that is, treatments delivering different dose distributions in different fractions, may lower treatment side effects without compromising tumor control. This is achieved by hypofractionating parts of…
The primary object of a phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent…
Given n experiment subjects with potentially heterogeneous covariates and two possible treatments, namely active treatment and control, this paper addresses the fundamental question of determining the optimal accuracy in estimating the…
An accurately identified maximum tolerated dose (MTD) serves as the cornerstone of successful subsequent phases in oncology drug development. Bayesian logistic regression model (BLRM) is a popular and versatile model-based dose-finding…
We study a new two-time-scale stochastic gradient method for solving optimization problems, where the gradients are computed with the aid of an auxiliary variable under samples generated by time-varying MDPs controlled by the underlying…
Intensity Modulated Radiation Therapy is an effective cancer treatment. Models based on the Generalized Equivalent Uniform Dose (gEUD) provide radiation plans with excellent planning target volume coverage and low radiation for organs at…
The root-cause diagnostics of product quality defects in multistage manufacturing processes often requires a joint identification of crucial stages and process variables. To meet this requirement, this paper proposes a novel penalized…
In a tie-breaker design (TBD), subjects with high values of a running variable are given some (usually desirable) treatment, subjects with low values are not, and subjects in the middle are randomized. TBDs are intermediate between…
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…
The I-SPY2 phase 2 clinical trial is a long-running platform trial that evaluates neoadjuvant treatments for locally advanced breast cancer, assigning subjects to novel agents using response-adaptive randomization. Recently, I-SPY2 was…
The primary objective of Phase I oncology trials is to assess the safety and tolerability of novel therapeutics. Conventional dose escalation methods identify the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). However,…
There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed…