Related papers: Joint TITE-CRM for Dual Agent Dose Finding Studies
A multicompartment mathematical model is presented with the goal of studying the role of dose-dense protocols in the context of combination cancer chemotherapy. Dose-dense protocols aim at reducing the period between courses of chemotherapy…
Phase 1-2 designs provide a methodological advance over phase 1 designs for dose finding by using both clinical response and toxicity. A phase 1-2 trial still may fail to select a truly optimal dose. because early response is not a perfect…
The primary objective of phase I cancer clinical trials is to evaluate the safety of a new experimental treatment and to find the maximum tolerated dose (MTD). We show that the MTD estimation problem can be regarded as a level set…
Safety evaluation is an essential component of clinical trials. To protect study participants, these studies often implement safety stopping rules that will halt the trial if an excessive number of toxicity events occur. Existing safety…
The initiation of dose optimization has driven a paradigm shift in oncology clinical trials to determine the optimal biological dose (OBD). Early-phase trials with randomized doses can facilitate additional investigation of the identified…
In precision medicine, Dynamic Treatment Regimes (DTRs) are treatment protocols that adapt over time in response to a patient's observed characteristics. A DTR is a set of decision functions that takes an individual patient's information as…
Traditionally, the major objective in phase I trials is to identify a working-dose for subsequent studies, whereas the major endpoint in phase II and III trials is treatment efficacy. The dose sought is typically referred to as the maximum…
Optimizing doses for multiple indications is challenging. The pooled approach of finding a single optimal biological dose (OBD) for all indications ignores that dose-response or dose-toxicity curves may differ between indications, resulting…
We consider a Bayesian framework based on "probability of decision" for dose-finding trial designs. The proposed PoD-BIN design evaluates the posterior predictive probabilities of up-and-down decisions. In PoD-BIN, multiple grades of…
Two useful strategies to speed up drug development are to increase the patient accrual rate and use novel adaptive designs. Unfortunately, these two strategies often conflict when the evaluation of the outcome cannot keep pace with the…
Phase I dose escalation trials in oncology generally aim to find the maximum tolerated dose (MTD). However, with the advent of molecular targeted therapies and antibody drug conjugates, dose limiting toxicities are less frequently observed,…
Traditional dose selection for oncology registration trials typically employs a one- or two-step single maximum tolerated dose (MTD) approach. However, this approach may not be appropriate for molecularly targeted therapy that tends to have…
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…
We consider estimation of an optimal individualized treatment rule from observational and randomized studies when a high-dimensional vector of baseline variables is available. Our optimality criterion is with respect to delaying expected…
In targeted poisoning attacks, an attacker manipulates an agent-environment interaction to force the agent into adopting a policy of interest, called target policy. Prior work has primarily focused on attacks that modify standard MDP…
We consider the optimal design problem for identifying effective dose combinations within drug combination studies where the effect of the combination of two drugs is investigated. Drug combination studies are becoming increasingly…
In different areas of research, multiple recurrent competing risks (RCR) are often observed on the same observational unit. For instance, different types of cancer relapses are observed on the same patient and several types of component…
Model-assisted designs have garnered significant attention in recent years due to their high accuracy in identifying the maximum tolerated dose (MTD) and their operational simplicity. To identify the MTD, they employ estimated dose limiting…
Phase I dose-finding trials are increasingly challenging as the relationship between efficacy and toxicity of new compounds (or combination of them) becomes more complex. Despite this, most commonly used methods in practice focus on…
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,…