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 中期数据监测对于长期数据的成功设计、实施和报告至关重要。 眼部疾病的随机临床试验是最常用的。 具有中期监测计划的研究方法，控制 I 类错误率，保护统计数据 然而，当患者的双眼（聚集）时。 包括在一项研究中，组序贯方法考虑了最佳的眼间相关性 据我们所知，基本上不存在所有设计选项（随机化两者的不同方式） 文献中的眼睛或患者的一只眼睛）在本申请中，通过双方的合作努力。 乔治华盛顿大学和威尔斯眼科医院，结合理论和应用统计 专业知识，我们建议开发和评估用于视觉研究的统一组序贯设计 适应所有可能的设计选项，同时考虑眼间相关性 研究中包括患者的眼睛，这些设计选项包括：1) 只有一只眼睛符合条件，并且 每人随机化；2) 配对眼设计；3) 配对眼设计加上一只眼睛的病例 仅；4) 两只眼睛位于同一研究组（集群），加上仅一只眼睛的病例；以及 5) 两只眼睛； 眼睛可以在同一只手臂上，也可以在不同的手臂上，加上仅贡献一只眼睛的盒子 - 统一设计， 包括前四种设计作为特殊情况。拟议的项目旨在实现以下目标。 具体目标：1）提出、研究和评估分组序贯试验的设计特性 聚类（视线水平）连续端点；2) 提出、调查和评估设计特性 对于具有集群（眼睛水平）二元终点的分组序贯试验，以及 3) 提出、调查； 并评估具有集群（眼睛水平）生存终点的组序贯试验的设计特性。 完成这些拟议目标将为研究人员提供一套新的统计工具 改进长期试验的设计和监测，并尽量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提前停止的决定。 通过以下步骤实现：1）严格建立所提出的理论属性 方法；2）通过广泛的模拟研究检查有限样本的性能； 3）将所提出的方法应用于来自真实示例眼部试验的临时数据（年龄相关眼 疾病研究、家庭眼部监测研究、早产儿视网膜病变的冷冻治疗 试验和早产儿视网膜病变的早期治疗研究）以证明其有用性 将制作实施新方法的计算机程序。 通过带有 Web 界面的 R Shiny 应用程序即可使用，以便从业者轻松访问和方便 将提供详细的使用指南和文档。