Clinical Trials Commons^™

Flexible Spatial Priors In Bayesian Neuroimaging: Gmrf, Nngp, And Deep Gmrf, Boyoung Hur

All Dissertations

Structural neuroimaging is essential for understanding neurological disorders such as Alzheimer’s disease, enabling accurate delineation of brain regions through image segmentation. Among various segmentation methods, multi-atlas-based approaches like label fusion have become leading techniques. In statistics, Bayesian hierarchical models for label fusion are increasingly favored for their ability to incorporate uncertainty and prior knowledge. Also, a key challenge in modeling neuroimaging data is spatial dependence among image voxels, making the choice of spatial prior critical—particularly in high-resolution settings where segmentation accuracy and computational efficiency are both essential.

This dissertation proposes fully Bayesian spatial hierarchical models that explore two flex- ible …

Emerging Clinical Role Of Tavapadon, A Novel Dopamine Partial Agonist, In The Treatment Of Parkinson’S Disease, Alan D. Kaye, Bennett M. Ford, Brennan M. Abbott, Kalob M. Broocks, Sofia Novacic, Sahar Shekoohi

School of Medicine Faculty Publications

Tavapadon, a novel oral dopamine-D1R/D5R partial agonist, has been studied in recent years for the treatment of late-stage development Parkinson’s disease (PD). Levodopa, a dopamine precursor that currently remains the gold-standard first-line therapy for PD motor symptoms, serves as a benchmark against emerging dopaminergic agents. By selectively activating D1-family receptors on direct-pathway medium neurons, Tavapadon differs in that it delivers levodopa-level motor benefit while avoiding its many D2R/D3R-mediated adverse effects. In placebo-controlled trials, Tavapadon produced clear, clinically meaningful gains in motor function and day-to-day activities, as captured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Recent late-stage results have revealed …

Evaluating Alpha Spending Functions Applied To Observational Time-To-Event Analysis, Moses Torgbenu

Electronic Theses and Dissertations

This thesis explores the theoretical foundation of the alpha spending approach and extends its application beyond the conventional setting of randomized controlled trials (RCTs) to observational studies with time to event analyses. In these less structured environments, key design parameters such as the total number of events are often unknown, posing challenges for the standard implementation of sequential analysis methods.

Through simulation studies, this research delivers several important contributions. First, it presents a modified approach that uses calendar time to define the timing of interim analyses while relying on event-based information to estimate the correlation among test statistics. This adjustment …

Innovative Methods For The Design And Analysis Of Phase Ii Clinical Trials, Feng Tian

Dissertations and Theses (Open Access)

Drug development has become increasingly time-consuming, costly, and risky in recent years. There is significant potential for improving clinical trial designs, particularly for phase II trials, which play a critical role in the drug development process. Innovative methods are especially necessary for addressing key challenges in phase II trials in terms of dose-ranging study, patient population selection, and decentralized clinical trials (DCTs). This dissertation presents a comprehensive set of methodologies that address these critical issues with three projects. The first project introduces a Bayesian adaptive dose-ranging design that integrates both efficacy and toxicity data to evaluate each dose comprehensively. The …

Dual-Criterion Dose Finding Designs For Phase I Clinical Trials, Yunlong Yang

Dissertations and Theses (Open Access)

The primary objective of Phase I oncology trials is to assess the safety and tolerability of novel therapeutics. Conventional dose escalation methods identify the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). However, as cancer therapies have evolved from chemotherapy to targeted therapies, these traditional methods have become problematic. Many targeted therapies rarely produce DLT and are administered over multiple cycles, potentially resulting in the accumulation of lower-grade toxicities, which can lead to intolerance, such as dose reduction or interruption. To address this issue, we proposed dual-criterion designs that find the MTD based on both DLT and non-DLT-caused intolerance. …

Strengthening The Paediatric Clinical Trial Ecosystem To Better Inform Policy And Programmes, James A. Berkley, Judd L. Walson, Glenda Gray, Fiona Russell, Zulfiqar Ahmed Bhutta, Per Ashorn, Shane A. Norris, Ebunoluwa A. Adejuyigbe, Rebecca Grais, Bernhards Ogutu

Institute for Global Health and Development

The first WHO Global Clinical Trials Forum was convened in November, 2023 to develop a shared vision of an effective global clinical trial infrastructure. The Paediatric Clinical Trials Working Group was formed to provide perspectives, identify challenges, and propose solutions to strengthen the paediatric clinical trials ecosystem. Participants represented paediatric disciplines, including infectious diseases, nutrition, neonatology, pharmacology, oncology, neurodevelopment, public health, and policy. Childhood diseases have profound lifelong effects on health, livelihoods, and societies. Investment in early childhood results in highly cost-effective changes to lifelong health, productivity, and human capital returns. Yet, there remain substantial gaps in knowledge on the …

Discounting Effect Size When Borrowing External Data In Clinical Studies, Zhuanzhuan Ma, Chul Ahn, Bin Wang, Xuefeng Li

Research Symposium

Background: When borrowing information from external data to augment a current trial, many available methods discount the sample size but retain the effect size from previous studies. Discounting the sample size is just one way to discount the prior information. It may not be appropriate if the underlying assumption of unbiased treatment effect does not hold, for example, when the treatment effect in the historical study is likely higher than the one expected in the current trial.

Methods: To tackle this potential issue, we study some methods to shrink the effect size from previous studies assuming that the prior effect …

Leveraging Bayesian And Classical Techniques For Survival Analysis Using The Weibull-Rayleigh Distribution, Mahmoud Mansour, Rashad El-Sagheer, Nagwa Mohamed

Basic Science Engineering

This paper contributes to an extensive analysis of the Weibull-Rayleigh distribution (WRD), including Bayesian inference for randomly censored data. The WRD is a versatile model that fits various types of survival data, especially in situations including censoring, commonly found in biostatistics and engineering reliability research. The research investigates the derivation of the WRD’s probability density and cumulative distribution functions, employing maximum likelihood estimation (MLE) and Bayesian estimating techniques to accurately infer parameters. Gamma priors are utilized in Bayesian analysis, and approximate Bayesian estimates are derived by Gibbs sampling and Lindley’s approximation methods. An actual dataset that represents leukemia-free survival times …

Machine Learning Models Leveraging Patient-Similarity And Clinical Temporality For Disease Prognoses, Ahmad F. Al Musawi

Theses and Dissertations

Electronic Health Records (EHRs) constitute a comprehensive and high-dimensional repository of clinical data, encompassing a wide array of patient-level information such as diagnoses, procedures, medications, laboratory results, and unstructured clinical narratives. These data hold immense potential for advancing predictive modeling in healthcare, including tasks such as disease progression modeling, hospital readmission prediction, and length of stay (LoS) estimation. However, the intrinsic complexity of EHR data—manifested in its heterogeneity, sparsity, and temporal dynamics—poses significant analytical challenges that limit the generalizability and interpretability of conventional machine learning models. Recent methodological advancements in deep learning and graph-based learning, particularly Graph Neural Networks (GNNs), …

A Two-Stage Design For Choosing Among Several Normal Treatments In Comparison With A Control: The Case Of Common, Known Variance, Samarasuriyage Sayura Sankalpa Senaratne

UNF Graduate Theses and Dissertations

A two-stage design is developed for comparing the means of multiple normally distributed treatment groups under a known common variance, with the aim of identifying the treatment with the highest mean while minimizing the expected sample size, a crucial consideration in clinical trials. The proposed methodology integrates elements of both hypothesis testing and selection procedures to achieve greater efficiency and decision-making power. In the initial stage, if no treatment exhibits a mean surpassing a predefined efficacy threshold, the trial is terminated early, conserving resources. If one or more treatments exceed the threshold, the procedure advances to a second stage, where …