Related papers: Response-adaptive dose-finding under model uncerta…
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…
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…
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…
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,…
We consider the problem of constructing optimal designs for population pharmacokinetics which use random effect models. It is common practice in the design of experiments in such studies to assume uncorrelated errors for each subject. In…
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…
In a Phase II dose-finding study with a placebo control, a new drug with several dose levels is compared with a placebo to test for the effectiveness of the new drug. The main focus of such studies often lies in the characterization of the…
Bayesian adaptive designs have gained popularity in all phases of clinical trials with numerous new developments in the past few decades. During the COVID-19 pandemic, the need to establish evidence for the effectiveness of vaccines,…
Toxicologists are often concerned with determining the dosage to which an individual can be exposed with an acceptable risk of adverse effect. These types of studies have been conducted widely in the past, and many novel approaches have…
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…
Understanding treatment effect heterogeneity has become an increasingly popular task in various fields, as it helps design personalized advertisements in e-commerce or targeted treatment in biomedical studies. However, most of the existing…
Adaptive designs have been proposed for clinical trials in which the nuisance parameters or alternative of interest are unknown or likely to be misspecified before the trial. Whereas most previous works on adaptive designs and mid-course…
We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding…
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…
Understanding the dose-response relation between a continuous treatment and the outcome for an individual can greatly drive decision-making, particularly in areas like personalized drug dosing and personalized healthcare interventions.…
In several applications such as databases, planning, and sensor networks, parameters such as selectivity, load, or sensed values are known only with some associated uncertainty. The performance of such a system (as captured by some…
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…
Adaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical and efficient. These benefits are achieved while preserving the integrity and validity of the…
Recently, phase II trials with multiple schedules (frequency of administrations) have become more popular, for instance in the development of treatments for atopic dermatitis. If the relationship of the dose and response is described by a…
Many drugs used therapeutically or recreationally induce tolerance: the effect of the substance decreases with repeated use. This phenomenon may reduce the efficacy of the substance unless dosage is increased beyond what is healthy for the…