Related papers: Improving Maximum Tolerated Dose Selection in Mode…
Background: Phase I dose-finding trials increasingly encounter delayed-onset toxicities, especially with immunotherapies and targeted agents. The time-to-event continual reassessment method (TITE-CRM) handles incomplete follow-up using…
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…
This work aims to study the generalizability of a pre-developed deep learning (DL) dose prediction model for volumetric modulated arc therapy (VMAT) for prostate cancer and to adapt the model to three different internal treatment planning…
In this paper, a methodology is proposed that enables to analyze the sensitivity of the outcome of a therapy to unavoidable high dispersion of the patient specific parameters on one hand and to the choice of the parameters that define the…
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…
One common approach for dose optimization is a two-stage design, which initially conducts dose escalation to identify the maximum tolerated dose (MTD), followed by a randomization stage where patients are assigned to two or more doses to…
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…
Model informed precision dosing (MIPD) is a Bayesian framework to individualize drug therapy based on prior knowledge and patient-specific monitoring data. Typically, prior knowledge results from controlled clinical trials with a more…
An optimal individualized treatment rule (ITR) is a function that takes a patient's characteristics, such as demographics, biomarkers, and treatment history, and outputs a treatment that is expected to give the best outcome for that…
Oncology dose-finding trials are shifting from identifying the maximum tolerated dose (MTD) to determining the optimal biological dose (OBD), driven by the need for efficient methods that consider both toxicity and efficacy. This is…
An important objective in biomedical risk assessment is estimation of minimum exposure levels that induce a pre-specified adverse response in a target population. The exposure/dose points in such settings are known as Benchmark Doses…
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…
With the development of novel therapies such as molecularly targeted agents and immunotherapy, the maximum tolerated dose paradigm that "more is better" does not necessarily hold anymore. In this context, doses and schedules of novel…
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)…
We identify three properties of the standard oncology phase I trial design or 3 + 3 design. We show that the standard design implicitly uses isotonic regression to estimate a maximum tolerated dose. We next illustrate the relationship…
A major practical impediment when implementing adaptive dose-finding designs is that the toxicity outcome used by the decision rules may not be observed shortly after the initiation of the treatment. To address this issue, we propose the…
Extreme value theory (EVT) is well suited to model extreme events, such as floods, heatwaves, or mechanical failures, which is required for reliability assessment of systems across multiple domains for risk management and loss prevention.…
Topology optimization (TO) serves as a widely applied structural design approach to tackle various engineering problems. Nevertheless, sensitivity-based TO methods usually struggle with solving strongly nonlinear optimization problems. By…
We propose a flexible design for the identification of optimal dose combinations in dual-agent dose-finding clinical trials. The design is called AAA, standing for three adaptations: adaptive model selection, adaptive dose insertion, and…
There has been an increasing interest in using interval-based Bayesian designs for dose finding, one of which is the modified toxicity probability interval (mTPI) method. We show that the decision rules in mTPI correspond to an optimal rule…