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We propose a data-dependent early completion of dose finding trials for drug-combination. The early completion is determined when a beta-binomial probability for dose retainment with the trial data and the number of remaining patients is…

Methodology · Statistics 2022-02-10 Masahiro Kojima

We propose a novel Phase I intra-patient dose-escalation design tailored for multi-cycle immunotherapy settings, in which toxicity at a fixed dose level is clinically expected to decrease over successive treatment cycles. This design was…

An important task in drug development is to identify patients, which respond better or worse to an experimental treatment. Identifying predictive covariates, which influence the treatment effect and can be used to define subgroups of…

Methodology · Statistics 2018-11-27 Marius Thomas , Björn Bornkamp , Katja Ickstadt

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…

Methodology · Statistics 2025-02-27 Gina DAngelo , Guannan Chen , Di Ran

The long-term efficacy of targeted therapeutics for cancer treatment can be significantly limited by the type of therapy and development of drug resistance, inter alia. Experimental studies indicate that the factors enhancing acquisition of…

Tissues and Organs · Quantitative Biology 2021-02-16 Joseph Malinzi , Kevin Bosire Basita , Sara Padidar , Henry A. Adeola

We propose a rule-based statistical design for combination dose-finding trials with two agents. The Ci3+3 design is an extension of the i3+3 design with simple decision rules comparing the observed toxicity rates and equivalence intervals…

Applications · Statistics 2023-03-29 Shijie Yuan , Tianjian Zhou , Yawen Lin , Yuan Ji

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…

Methodology · Statistics 2018-07-24 Ruitao Lin , Ying Yuan

Designing modern oncology trials requires synthesizing evidence from prior studies to inform hypothesis generation and sample size determination. Trial designs based on incomplete or imprecise summaries can lead to misspecified hypotheses…

Many phase II clinical trials have used survival outcomes as the primary endpoints in recent decades. Suppose the radiotherapy is evaluated in a phase II trial using survival outcomes. In that case, the competing risk issue often arises…

Applications · Statistics 2022-03-15 Jina Park , Wenjing Hu , Ick Hoon Jin , Hao Liu , Yong Zang

In early-phase cancer clinical trials, the limited availability of data presents significant challenges in developing a framework to efficiently quantify treatment effectiveness. To address this, we propose a novel utility-based Bayesian…

Methodology · Statistics 2025-06-10 Saurabh Bhandari , Michael J. Daniels , Chenguang Wang

This study investigates the estimation and the statistical inference about Conditional Average Treatment Effects (CATEs), which have garnered attention as a metric representing individualized causal effects. In our data-generating process,…

Methodology · Statistics 2024-03-07 Masahiro Kato

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…

Methodology · Statistics 2020-10-27 Piaomu Liu

In medical practice, treatments are selected based on the expected causal effects on patient outcomes. Here, the gold standard for estimating causal effects are randomized controlled trials; however, such trials are costly and sometimes…

Machine Learning · Statistics 2023-01-24 Dennis Frauen , Tobias Hatt , Valentyn Melnychuk , Stefan Feuerriegel

Model-assisted interval designs such as the Keyboard design are transparent and easy to implement in phase I oncology trials. However, interim decisions based solely on data from the current dose may overlook informative signals from…

Applications · Statistics 2026-05-26 Jiangyan Zhao , Xian Shi , Jin Xu

In this review we address to what extent computational techniques can augment our ability to predict toxicity. The first section provides a brief history of empirical observations on toxicity dating back to the dawn of Sumerian…

Molecular Networks · Quantitative Biology 2018-01-17 Narsis A. Kiani , Ming-Mei Shang , Hector Zenil , Jesper Tegnér

The uncertainty of classification outcomes is of crucial importance for many safety critical applications including, for example, medical diagnostics. In such applications the uncertainty of classification can be reliably estimated within a…

Artificial Intelligence · Computer Science 2007-05-23 V. Schetinin , J. E. Fieldsend , D. Partridge , W. J. Krzanowski , R. M. Everson , T. C. Bailey , A. Hernandez

Estimating heterogeneous treatment effects in survival settings is complicated by right censoring as well as the time-varying nature of the estimand. While the conditional average treatment effect (CATE) provides a natural target, most…

Methodology · Statistics 2026-04-14 Yuming Sun , Jian Kang , Yi Li

Identifying the mutations that drive cancer growth is key in clinical decision making and precision oncology. As driver mutations confer selective advantage and thus have an increased likelihood of occurrence, frequency-based statistical…

Genomics · Quantitative Biology 2021-05-04 Adnan Akbar , Andrey Solovyev , John W Cassidy , Nirmesh Patel , Harry W Clifford

Tracer-kinetic analysis of dynamic contrast-enhanced magnetic resonance imaging data is commonly performed with the well-known Tofts model and nonlinear least squares (NLLS) regression. This approach yields point estimates of model…

Medical Physics · Physics 2020-01-08 Andreas Mittermeier , Birgit Ertl-Wagner , Jens Ricke , Olaf Dietrich , Michael Ingrisch

Detecting predictive biomarkers from multi-omics data is important for precision medicine, to improve diagnostics of complex diseases and for better treatments. This needs substantial experimental efforts that are made difficult by the…

Quantitative Methods · Quantitative Biology 2021-06-08 Betül Güvenç Paltun , Samuel Kaski , Hiroshi Mamitsuka