相关论文: Learning for Dose Allocation in Adaptive Clinical …
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 early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…
Recently, the strategy for dose optimization in oncology has shifted to conduct Phase 2 randomized controlled trials with multiple doses. Optimal biologic dose selection from Phase 1 trial data to determine candidate doses for Phase 2…
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…
Phase-3 clinical trials provide the highest level of evidence on drug safety and effectiveness needed for market approval by implementing large randomized controlled trials (RCTs). However, 30-40% of these trials fail mainly because such…
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…
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…
The US FDA's Project Optimus initiative that emphasizes dose optimization prior to marketing approval represents a pivotal shift in oncology drug development. It has a ripple effect for rethinking what changes may be made to conventional…
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…
We present a graphical, knowledge-based method for reviewing treatment-emergent adverse events (AEs) in clinical trials. The approach enhances MedDRA by adding a hidden medical knowledge layer (Safeterm) that captures semantic relationships…
Nonlinear regression models addressing both efficacy and toxicity outcomes are increasingly used in dose-finding trials, such as in pharmaceutical drug development. However, research on related experimental design problems for corresponding…
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…
Clinical trials in the medical domain are constrained by budgets. The number of patients that can be recruited is therefore limited. When a patient population is heterogeneous, this creates difficulties in learning subgroup specific…
Dose-finding clinical trials in oncology aim to estimate the maximum tolerated dose (MTD), based on safety traditionally obtained from the clinician's perspective. While the collection of patient-reported outcomes (PROs) has been advocated…
We study the problem of finding the optimal dosage in early stage clinical trials through the multi-armed bandit lens. We advocate the use of the Thompson Sampling principle, a flexible algorithm that can accommodate different types of…
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…
Adaptive experimental designs have gained popularity in clinical trials and online experiments. Unlike traditional, fixed experimental designs, adaptive designs can dynamically adjust treatment randomization probabilities and other design…
In oncology phase I trials, model-assisted designs have been increasingly adopted because they enable adaptive yet operationally simple dose adjustment based on accumulating safety data, leading to a paradigm shift in dose-escalation…
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)…
Nowadays, more and more clinical trials choose combinational agents as the intervention to achieve better therapeutic responses. However, dose-finding for combinational agents is much more complicated than single agent as the full order of…