Design Considerations for Two-Phase Studies

描述（由申请人提供）：在确定暴露与疾病之间的关联方面，研究人员可以使用各种各样的研究设计。虽然两阶段研究已被证明提供了显着的效率增益比传统的病例对照设计，他们还没有被广泛采用。最近一项对自2002年以来发表在五种流行病学/医学顶级期刊上的4,792项研究的调查发现，只有一项研究采用了两阶段设计。部分原因可能是缺乏关于如何设计和规划两阶段研究的出版指南，以及没有通用软件的实际困难。为了解决这些问题，并广泛使用两阶段研究，本研究提出了一个灵活的框架，调查设计考虑的背景下，规划两阶段研究。这将涉及两个步骤;（i）发展一个概念架构，涵盖规划阶段所需的决定;及（ii）发展一个以算法模拟为基础的架构，方便研究在不同情况下的潜在选择。在此基础上，我们建议进行广泛而全面的模拟研究，以探讨与两阶段研究设计相关的各种选择的影响。这项提案的动机是由乳腺癌监测联盟（BCSC）正在进行的和未来的研究。随着BCSC内科学研究的新机会的出现，必须尽可能充分利用现有的数据库/基础设施。两阶段设计为实现这一目标提供了一个框架，改进对此类研究的规划和设计的指导，对于今后进行具有成本效益但又具有强大统计功能的研究至关重要。因此，这项工作的一个关键组成部分将是传播方法和结果，并提供软件;将在常用的统计软件包中开发算法/代码和文件，并向公众提供。

DESCRIPTION (provided by applicant): In identifying associations between exposures and diseases researchers have a wide variety of study designs at their disposal. Although two-phase studies have been shown to provide substantial efficiency gains over the traditional case-control design, they have not been widely adopted. A recent survey of 4,792 studies in five top-line epidemiological/medical journals, published since 2002, found just a single study having employed the two-phase design. This may be due, in part, to a lack of published guidance on how to design and plan a two-phase study and the practical difficulties of not having general-purpose software. To address these issues and broad the use of two-phase studies, this research proposes to develop a flexible framework for investigating design considerations in the context of planning a two-phase study. This will involve two steps; (i) development of a conceptual framework which encompasses the decisions required at the planning stage and (ii) developing an algorithmic simulation-based framework which facilitates the investigation of potential choices in a variety of settings. Building on this, we propose to conduct an extensive and comprehensive simulation study to explore the impact of various choices associated with the design of a two-phase study. This proposal is motivated by ongoing and future research conducted by the Breast Cancer Surveillance Consortium (BCSC). As new opportunities for scientific research within the BCSC arise it will be important to make the best possible use of the existing database/infrastructure. The two-phase design provides a framework to achieve this, and improved guidance on the planning and design of such studies will be crucial for future cost-effective and yet statistically powerful studies. A key component of this work, therefore, will be the dissemination of methods and results, and the delivery of software; algorithms/code, together with documentation, will be developed in commonly used statistical packages and made publicly available.