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: 10682609
• 负责人: Guoqing Diao
• 金额: $ 25.11万
• 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/10682609
• 关键词: Accounting; Ancillary Study; Clinical Trials; Cold Therapy; Data; Data Correlations; Devices; Documentation; Early treatment; Eligibility Determination; Eye; Eye diseases; Futility; Glaucoma; Grant; Guidelines; Home; Hospitals; Lead; Literature; Methodology; Methods; Monitor; Negative Finding; Patients; Performance; Persons; Pharmaceutical Preparations; Property; Randomized; Reporting; Research Personnel; Retinopathy of Prematurity; Safety; Sample Size; Sampling; Treatment Efficacy; Universities; Vision research; Washington; age related; arm; computer program; data sharing; design; efficacy evaluation; follow-up; improved; longitudinal design; novel; randomized trial; randomized, clinical trials; 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.

摘要 临时数据监控对于成功设计、实施和报告长期 眼科疾病的随机临床试验。分组序贯方法是最常用的方法 控制第I类错误率、保护统计的临时监测计划的研究方法 电源，并避免错误的正/负fi赋值。然而，当患者的两只眼睛(聚集)时 均纳入一项研究，以分组序贯方法占眼间相关性最好 据我们所知，基本上并不是所有的设计选项都存在(将两者随机化的不同方法 眼睛或病人的一只眼睛)。在此应用程序中，通过 乔治华盛顿大学和威尔斯眼科医院，理论和应用统计学相结合 专业知识，我们建议开发和评估用于视觉研究的单一fi组序贯设计 这包含了所有可能的设计选项，同时考虑了眼睛之间的相关性 这项研究包括患者的眼睛。这些设计选项包括：1)仅一只符合条件的眼睛和 每人随机配对；2)配对眼睛设计；3)配对眼睛设计加一只眼睛的病例 仅；4)同一研究臂上的两只眼睛(集群)加上仅贡献一只眼睛的病例；以及5)两只眼睛 眼睛在相同或不同的手臂上，加上只有一只眼睛的情况-Unified设计，这是 包括fi的前四个设计作为特例。拟议的项目旨在实现以下目标 SPECIfic目标：1)提出、调查和评估分组序贯试验的设计属性 群集(视线水平)连续端点；2)建议、调查和评估设计属性 针对群集化(眼睛水平)二元终点的分组序贯试验；以及3)提出、研究 并评估具有群集化(眼睛水平)生存终点的分组序贯试验的设计特性。 这些拟议目标的完成将为调查人员提供一套新的统计工具 改进长期试验的设计和监测，将临时试验的可能性降至最低 可能导致不必要的继续研究或提前停止研究的决定。每个特定的fic目标都将是 通过以下几个步骤来实现：1)严谨地确立了提出的理论属性 方法；2)通过广泛的模拟研究来检验fiNITE样本的性能；以及 3)将所提出的方法应用于来自实际眼部试验(年龄相关的眼部)的临时数据 疾病研究、家庭眼科监测研究、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)以证明其有效性 所提出的方法。将编制实施新方法的计算机程序 通过带有Web界面的R闪亮应用程序提供，从业者可以轻松访问和方便 使用。将提供详细的使用指南和文档。