Related papers: Joint TITE-CRM for Dual Agent Dose Finding Studies
The study of combinations of drugs/drug-schedules gained increasing attention in various therapeutic areas recently. In oncology, the aim of phase I combination clinical trial is to find the maximum tolerated combination (MTC). Many…
This paper proposes a novel criterion for the allocation of patients in Phase~I dose-escalation clinical trials aiming to find the maximum tolerated dose (MTD). Conventionally, using a model-based approach the next patient is allocated to…
Broadening eligibility criteria in cancer trials has been advocated to represent the true patient population more accurately. While the advantages are clear in terms of generalizability and recruitment, novel dose-finding designs are needed…
In the development of new cancer treatment, an essential step is to determine the maximum tolerated dose (MTD) via phase I clinical trials. Generally speaking, phase I trial designs can be classified as either model-based or algorithm-based…
Conventionally, a first-in-human phase I trial in healthy volunteers aims to confirm the safety of a drug in humans. In such situations, volunteers should not suffer from any safety issues and simple algorithm-based dose-escalation schemes…
Observational cohort studies are increasingly being used for comparative effectiveness research to assess the safety of therapeutics. Recently, various doubly robust methods have been proposed for average treatment effect estimation by…
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…
In multi-agent reinforcement learning, multiple agents learn simultaneously while interacting with a common environment and each other. Since the agents adapt their policies during learning, not only the behavior of a single agent becomes…
We consider applying multi-armed bandits to model-assisted designs for dose-finding clinical trials. Multi-armed bandits are very simple and powerful methods to determine actions to maximize a reward in a limited number of trials. Among the…
Identification of optimal dose combinations in early phase dose-finding trials is challenging, due to the trade-off between precisely estimating the many parameters required to flexibly model the possibly non-monotonic dose-response…
Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing…
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…
An unprecedented number of new cancer targets are in development, and most are being developed in combination therapies. Early oncology development is strategically challenged in choosing the best combinations to move forward to late stage…
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…
In placebo-controlled randomized trials, the post-randomization use of concomitant medications may be higher in the placebo arm than in the treatment arm. This may dilute the full benefits of the randomized drug as estimated by the…
Phase I clinical trials are designed to test the safety (non-toxicity) of drugs and find the maximum tolerated dose (MTD). This task becomes significantly more challenging when multiple-drug dose-combinations (DC) are involved, due to the…
Phase I dose-escalation trials constitute the first step in investigating the safety of potentially promising drugs in humans. Conventional methods for phase I dose-escalation trials are based on a single treatment schedule only. More…
A fundamental model of tumor growth in the presence of cytotoxic chemotherapeutic agents is formulated. The model allows to study the role of the Norton-Simon hypothesis in the context of dose-dense chemotherapy. Dose-dense protocols aim at…
Immunotherapies and targeted therapies have gained popularity due to their promising therapeutic effects across multiple treatment areas. The focus of early phase dose-finding clinical trials has shifted from finding the maximum tolerated…
Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision-making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls…