Unified group sequential designs for clustered data (eye level) in randomized eye trials

随机眼科试验中聚类数据（眼水平）的统一组序贯设计

• 批准号: 10527031
• 负责人: Guoqing Diao
• 金额: $ 21.08万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527031
• 关键词: Accounting; Ancillary Study; Clinical Trials; Cold Therapy; Data; Devices; Documentation; Early treatment; Eye; Eye diseases; Futility; Glaucoma; Gold; Grant; Guidelines; Home; Hospitals; Lead; Literature; Methodology; Methods; Monitor; Negative Finding; Patients; Performance; Persons; Pharmaceutical Preparations; Property; Randomized; Randomized Clinical Trials; Reporting; Research Personnel; Retinopathy of Prematurity; Safety; Sample Size; Sampling; Universities; Vision research; Washington; age related; arm; base; computer program; data sharing; design; efficacy evaluation; follow-up; improved; longitudinal design; novel; randomized trial; simulation; theories; tool; treatment arm; treatment effect; user-friendly; web interface

ABSTRACT Interim data monitoring is essential to the successful design, conduct, and reporting of long-term randomized clinical trials for eye diseases. Group sequential methods are the most commonly used methods for studies with interim monitoring plans, which control type I error rate, protect statistical power, and avoid false positive/negative findings. However, when both eyes (clustered) from a patient are included in a study, group sequential methods accounting for the inter-eye correlation to the best of our knowledge, essentially do not exist for all design options (different ways of randomizing both eyes or one eye of a patient) in the literature. In this application, through a collaborative effort between George Washington University and Wills Eye Hospital, that combines theoretical and applied statistical expertise, we propose to develop and evaluate a unified group sequential design for vision research that accommodates all possible design options while accounting for inter-eye correlations when both eyes of a patient are included in the study. These design options include: 1) only one eye eligible and randomized per person; 2) paired eye design; 3) paired eye design plus cases contributing one eye only; 4) both eyes on the same study arm (clustered) plus cases contributing one eye only; and 5) two eyes either on the same or different arms plus cases contributing one eye only - unified design, which includes the first four designs as special cases. The proposed project aims to achieve the following specific aims: 1) to propose, investigate and evaluate design properties for group sequential trials with clustered (eye level) continuous endpoints; 2) to propose, investigate and evaluate design properties for group sequential trials with clustered (eye level) binary endpoints; and 3) to propose, investigate and evaluate design properties for group sequential trials with clustered (eye level) survival endpoints. Completion of these proposed aims will provide investigators with a new suite of statistical tools to improve the design and monitoring of long-term trials and minimize the likelihood of making interim decisions that might lead to unnecessary study continuation or early stopping. Each specific aim will be achieved through the following steps: 1) rigorously establish the theoretical properties of the proposed methodology; 2) examine the finite-sample performance through extensive simulation studies; and 3) apply the proposed methods to interim data from real example eye trials (the Age-Related Eye Disease Study, the HOme Monitoring of the Eye Study, the Cryotherapy for Retinopathy of Prematurity Trial, and the Early Treatment for Retinopathy of Prematurity Study) to demonstrate the usefulness of the proposed methods. Computer programs implementing the new methodology will be made available through an R Shiny App with a web interface for practitioners' easy access and convenient use. Detailed usage guides and documentation will be provided.

抽象的 临时数据监视对于长期的成功设计，进行和报告至关重要 眼病的随机临床试验。组顺序方法是最常用的 使用临时监测计划的研究方法，哪些控制I型错误率，保护统计 权力，避免误报/负面发现。但是，当两只眼睛（聚集）的患者 包含在研究中 关于我们的知识，本质上并不存在所有设计选项（不同的随机方法 文献中的眼睛或一只患者的眼睛）。在此应用程序中，通过 乔治华盛顿大学和威尔斯眼科医院，结合了理论和应用统计 专业知识，我们建议开发和评估视力研究的统一群体顺序设计 当两者都会考虑双方相关性时，可以满足所有可能的设计选项 患者的眼睛包括在研究中。这些设计选项包括：1）只有一只眼睛的资格 每人随机分配； 2）配对的眼睛设计； 3）配对的眼睛设计加上一只眼睛的箱子 仅有的; 4）双眼在同一研究臂上（聚类）加上仅造成一只​​眼睛的病例； 5）两个 眼睛在相同或不同的手臂上加上只有一只眼睛的案例 - 统一的设计， 包括第一个四个设计作为特殊情况。拟议的项目旨在实现以下 特定目的：1）提出，调查和评估与小组顺序试验的设计特性 聚类（眼级）连续端点； 2）提出，调查和评估设计特性 用于群集（眼级）二进制端点的组顺序试验； 3）提议，调查 并评估具有簇状（眼平）生存终点的组顺序试验的设计属性。 这些拟议的目标的完成将为调查人员提供一套新的统计工具 改善长期试验的设计和监测，并最大程度地减少进行临时试验的可能性 可能导致不必要的研究继续或早期停止的决定。每个特殊目标都是 通过以下步骤实现：1）严格建立所提出的理论特性 方法论； 2）通过广泛的模拟研究检查有限样本的性能；和 3）将提出的方法应用于实际示例眼试验的临时数据（与年龄相关的眼睛 疾病研究，眼睛研究的家庭监测，早产视网膜病变的冷冻疗法 试验和早产性视网膜病变的早期治疗）证明了有用性 提出的方法。将制定实施新方法的计算机程序 可通过带有R Shiny应用的带有Web界面可用，可用于从业人员轻松访问和方便 使用。将提供详细的用法指南和文档。