相关论文: A Bayesian hierarchical model for bridging across …
Leveraging preclinical animal data for a phase I first-in-man trial is appealing yet challenging. A prior based on animal data may place large probability mass on values of the dose-toxicity model parameter(s), which appear infeasible in…
Basket trials have gained increasing attention for their efficiency, as multiple patient subgroups are evaluated simultaneously. Conducted basket trials focus primarily on establishing the early efficacy of a treatment, yet continued…
Hierarchical Bayesian methods enable information sharing across multiple related regression problems. While standard practice is to model regression parameters (effects) as (1) exchangeable across datasets and (2) correlated to differing…
In this paper, we develop a graphical modeling framework for the inference of networks across multiple sample groups and data types. In medical studies, this setting arises whenever a set of subjects, which may be heterogeneous due to…
In pre- and non-clinical toxicology, the reduction of animal use is highly desireable. Although approaches for possible sample size reduction in the concurrent control group were suggested previously under the virtual control groups…
Biomedical data, particularly in the field of genomics, has characteristics which make it challenging for machine learning applications - it can be sparse, high dimensional and noisy. Biomedical applications also present challenges to model…
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…
Phase I dose-escalation trials must be guided by a safety model in order to avoid exposing patients to unacceptably high risk of toxicities. Traditionally, these trials are based on one type of schedule. In more recent practice, however,…
Translating potential disease biomarkers between multi-species 'omics' experiments is a new direction in biomedical research. The existing methods are limited to simple experimental setups such as basic healthy-diseased comparisons. Most of…
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…
The analysis of data from multiple experiments, such as observations of several individuals, is commonly approached using mixed-effects models, which account for variation between individuals through hierarchical representations. This makes…
Hierarchical model fitting has become commonplace for case-control studies of cognition and behaviour in mental health. However, these techniques require us to formalise assumptions about the data-generating process at the group level,…
In preclinical investigations, e.g. in in vitro, in vivo and in silico studies, the pharmacokinetic, pharmacodynamic and toxicological characteristics of a drug are evaluated before advancing to first-in-man trial. Usually, each study is…
Surrogate endpoints play an important role in drug development when they can be used to measure treatment effect early compared to the final clinical outcome and to predict clinical benefit or harm. Such endpoints are assessed for their…
Animal-vehicle collisions (AVCs) are common around the world and result in considerable loss of animal and human life, as well as significant property damage and regular insurance claims. Understanding their occurrence in relation to…
Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main…
The analysis of longitudinal categorical data can be complex and unfeasible due to the number of parameters involved, characterised by overparameterisation leading to model non-convergence, in addition to problems related to sample size and…
In Oncology, trials evaluating drug combinations are becoming more common. While combination therapies bring the potential for greater efficacy, they also create unique challenges for ensuring drug safety. In Phase-I dose escalation trials…
Infectious disease dynamics operate across multiple biological scales, with within-host viral dynamics being a key driver of between-host transmission. However, while models that explicitly link these scales exist, none have been developed…
The planning and conduct of animal experiments in the European Union is subject to strict legal conditions. Still, many preclinical animal experiments are only poorly designed. As a consequence, discoveries that are made in one animal…