Design Considerations for Two-Phase Studies

为了确定暴露与疾病之间的联系，研究人员有各种各样的研究设计可供选择。虽然两阶段研究已被证明比传统的病例对照设计提供了实质性的效率提高，但它们尚未被广泛采用。最近一项对2002年以来发表在五家顶级流行病学/医学期刊上的4792项研究的调查发现，只有一项研究采用了两阶段设计。这可能部分是由于缺乏关于如何设计和计划两阶段研究的公开指导，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，本研究建议开发一个灵活的框架，用于在规划两阶段研究的背景下调查设计考虑因素。这将涉及两个步骤；(i)制定一个概念框架，其中包括规划阶段所需的决策；（ii）制定一个基于算法模拟的框架，以促进对各种环境下潜在选择的调查。在此基础上，我们建议进行一项广泛而全面的模拟研究，以探索与两阶段研究设计相关的各种选择的影响。这项提议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内部科学研究的新机会出现，重要的是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将对未来具有成本效益且具有统计效力的研究至关重要。因此，这项工作的一个关键组成部分将是方法和结果的传播以及软件的交付；算法/代码连同文件将编制成常用的统计包，并向公众提供。

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.