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An essential component of therapeutic drug/biomarker monitoring (TDM) is to combine patient data with prior knowledge for model-based predictions of therapy outcomes. Current Bayesian forecasting tools typically rely only on the most…

Quantitative Methods · Quantitative Biology 2019-09-23 Corinna Maier , Niklas Hartung , Jana de Wiljes , Charlotte Kloft , Wilhelm Huisinga

The primary object of a phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent…

Methodology · Statistics 2014-05-07 Joseph S. Koopmeiners , Andrew Wey

Data augmentation is an essential part of the training process applied to deep learning models. The motivation is that a robust training process for deep learning models depends on large annotated datasets, which are expensive to be…

Computer Vision and Pattern Recognition · Computer Science 2017-10-31 Toan Tran , Trung Pham , Gustavo Carneiro , Lyle Palmer , Ian Reid

In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and efficacious that maximises some optimality criterion based on safety and efficacy. This is further complicated when…

Applications · Statistics 2022-03-31 Helen Barnett , Oliver Boix , Dimitris Kontos , Thomas Jaki

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…

Applications · Statistics 2023-04-03 Anaïs Andrillon , Lucie Biard , Shing M. Lee

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…

Methodology · Statistics 2026-02-24 Robert Amevor , Emmanuel Kubuafor , Dennis Baidoo

Phase I clinical trials are essential to bringing novel therapies from chemical development to widespread use. Traditional approaches to dose-finding in Phase I trials, such as the '3+3' method and the Continual Reassessment Method (CRM),…

Methodology · Statistics 2024-03-04 Luka Kovacevic , Thomas Jaki , Helen Barnett , Pavel Mozgunov

Drug combination trials are increasingly common nowadays in clinical research. However, very few methods have been developed to consider toxicity attributions in the dose escalation process. We are motivated by a trial in which the…

Methodology · Statistics 2018-08-23 Jose L. Jimenez , Mourad Tighiouart , Mauro Gasparini

An efficient monotone data augmentation (MDA) algorithm is proposed for missing data imputation for incomplete multivariate nonnormal data that may contain variables of different types, and are modeled by a sequence of regression models…

Methodology · Statistics 2018-11-21 Yongqiang Tang

In recent years, deep learning has achieved remarkable achievements in many fields, including computer vision, natural language processing, speech recognition and others. Adequate training data is the key to ensure the effectiveness of the…

Machine Learning · Computer Science 2019-05-24 Chunxu Zhang , Jiaxu Cui , Bo Yang

In traditional dose-finding studies, dose-limiting toxicity (DLT) is determined within a fixed time observation window where DLT is often defined as a binary outcome. In the setting of oncology dose-finding trials, often patients in…

Applications · Statistics 2019-09-09 Lucie Biard , Bin Cheng , Gulam A. Manji , Shing M. Lee

This work introduces the Burdened Bayesian Logistic Regression Model (BBLRM), an enhancement of the Bayesian Logistic Regression Model (BLRM) for dose-finding in phase I oncology trials. The BLRM determines the maximum tolerated dose (MTD)…

Methodology · Statistics 2025-08-18 Andrea Nizzardo , Luca Genetti , Marco Pergher

Model-informed precision dosing (MIPD) using therapeutic drug/biomarker monitoring offers the opportunity to significantly improve the efficacy and safety of drug therapies. Current strategies comprise model-informed dosing tables or are…

Machine Learning · Statistics 2020-06-02 Corinna Maier , Niklas Hartung , Charlotte Kloft , Wilhelm Huisinga , Jana de Wiljes

Data augmentation (DA) turns seemingly intractable computational problems into simple ones by augmenting latent missing data. In addition to computational simplicity, it is now well-established that DA equipped with a deterministic…

Methodology · Statistics 2020-05-26 Hyungsuk Tak , Kisung You , Sujit K. Ghosh , Bingyue Su , Joseph Kelly

When treatment policy estimands are of interest, clinical trials often attempt to collect patient data after intercurrent events (ICEs), although such data are often limited. Retrieved dropout imputation methods, which use pre-ICE and…

Methodology · Statistics 2026-03-31 Brendah Nansereko , Marcel Wolbers , James R. Carpenter , Jonathan W. Bartlett

An accurately identified maximum tolerated dose (MTD) serves as the cornerstone of successful subsequent phases in oncology drug development. Bayesian logistic regression model (BLRM) is a popular and versatile model-based dose-finding…

Methodology · Statistics 2021-05-17 Hongtao Zhang , Alan Y Chiang , Jixian Wang

To achieve the goal of providing the best possible care to each patient, physicians need to customize treatments for patients with the same diagnosis, especially when treating diseases that can progress further and require additional…

Methodology · Statistics 2022-10-25 Xiao Li , Brent R Logan , S M Ferdous Hossain , Erica E M Moodie

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…

Methodology · Statistics 2018-07-17 Pavel Mozgunov , Thomas Jaki

This study proposes a new Bayesian approach to infer binary treatment effects. The approach treats counterfactual untreated outcomes as missing observations and infers them by completing a matrix composed of realized and potential untreated…

Methodology · Statistics 2021-04-20 Masahiro Tanaka

Trial-based economic evaluations are typically performed on cross-sectional variables, derived from the responses for only the completers in the study, using methods that ignore the complexities of utility and cost data (e.g. skewness and…

Methodology · Statistics 2018-05-21 Andrea Gabrio , Michael J. Daniels , Gianluca Baio
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