相关论文: Evaluating hybrid controls methodology in early-ph…

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…

Clinical trials are an instrument for making informed decisions based on evidence from well-designed experiments. Here we consider adaptive designs mainly from the perspective of multi-arm Phase II clinical trials, in which one or more…

Traditional phase I dose finding cancer clinical trial designs aim to determine the maximum tolerated dose (MTD) of the investigational cytotoxic agent based on a single toxicity outcome, assuming a monotone dose-response relationship.…

In pharmaceutical and toxicological research, historical control data are increasingly used to validate concurrent control groups, typically via the construction of historical control limits. While methods have been described for continuous…

During drug development, evidence can emerge to suggest a treatment is more effective in a specific patient subgroup. Whilst early trials may be conducted in biomarker-mixed populations, later trials are more likely to enrol…

In this paper, a Bayesian approach is developed for simultaneously comparing multiple experimental treatments with a common control treatment in an exploratory clinical trial. The sample size is set to ensure that, at the end of the study,…

Treatment selection in breast cancer is guided by molecular subtypes and clinical characteristics. However, current tools including genomic assays lack the accuracy required for optimal clinical decision-making. We developed a novel…

Breast cancer is a leading cause of cancer-related mortality worldwide, and timely accurate diagnosis is critical to improving survival outcomes. While convolutional neural networks (CNNs) have demonstrated strong performance on…

Given the prominence of targeted therapy and immunotherapy in cancer treatment, it becomes imperative to consider heterogeneity in patients' responses to treatments, which contributes greatly to the widely used proportional hazard…

Recently a new experimental approach, the hybrid experimental design (HED), was introduced to enable investigators to answer scientific questions about building behavioral interventions in which human-delivered and digital components are…

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…

In response to the U.S.\ Food and Drug Administration's (FDA) Project Optimus, a paradigm shift is underway in the design of early-phase oncology trials. To accelerate drug development, seamless Phase I/II designs have gained increasing…

For many patients, current ovarian cancer treatments offer limited clinical benefit. For some therapies, it is not possible to predict patients' responses, potentially exposing them to the adverse effects of treatment without any…

In two harmonized efficacy studies to prevent HIV infection through multiple infusions of the monoclonal antibody VRC01, a key objective is to evaluate whether the serum concentration of VRC01, which changes cyclically over time along with…

FDA's Project Optimus initiative for oncology drug development emphasizes selecting a dose that optimizes both efficacy and safety. When an inferentially adaptive Phase 2/3 design with dose selection is implemented to comply with the…

Tuberculosis (TB) is a major global health challenge, and is compounded by co-morbidities such as HIV, diabetes, and anemia, which complicate treatment outcomes and contribute to heterogeneous patient responses. Traditional models of TB…

Cell heterogeneity plays an important role in patient responses to drug treatments. In many cancers, it is associated with poor treatment outcomes. Many modern drug combination therapies aim to exploit cell heterogeneity, but determining…

This paper presents a new type of hybrid model for Bayesian optimization (BO) adept at managing mixed variables, encompassing both quantitative (continuous and integer) and qualitative (categorical) types. Our proposed new hybrid models…

A mathematical model for time development of metastases and their distribution in size and carrying capacity is presented. The model is used to theoretically investigate anti-cancer therapies such as surgery and chemical treatments…

Nearly a quarter of visits to the Emergency Department are for conditions that could have been managed via outpatient treatment; improvements that allow patients to quickly recognize and receive appropriate treatment are crucial. The…