Wild Pascal, Andrieu Nadine, Goldstein Alisa M, Schill Walter
INRS, French National Institute for Research and Safety, Department of Epidemiology, France.
Epidemiol Perspect Innov. 2008 Oct 1;5:4. doi: 10.1186/1742-5573-5-4.
The two-phase design consists of an initial (Phase One) study with known disease status and inexpensive covariate information. Within this initial study one selects a subsample on which to collect detailed covariate data. Two-phase studies have been shown to be efficient compared to standard case-control designs. However, potential problems arise if one cannot assure minimum sample sizes in the rarest categories or if recontact of subjects is difficult. In the case of a rare exposure with an inexpensive proxy, the authors propose the flexible two-phase design for which there is a single time of contact, at which a decision about full covariate ascertainment is made based on the proxy. Subjects are screened until the desired numbers of cases and controls have been selected for full data collection. Strategies for optimizing the cost/efficiency of this design and corresponding software are presented. The design is applied to two examples from occupational and genetic epidemiology. By ensuring minimum numbers for the rarest disease-covariate combination(s), we obtain considerable efficiency gains over standard two-phase studies with an improved practical feasibility. The flexible two-phase design may be the design of choice in the case of well targeted studies of the effect of rare exposures with an inexpensive proxy.
两阶段设计由一项初始（第一阶段）研究组成，该研究具有已知的疾病状态和低成本的协变量信息。在这项初始研究中，选择一个子样本以收集详细的协变量数据。与标准病例对照设计相比，两阶段研究已被证明是有效的。然而，如果无法确保最罕见类别中的最小样本量，或者如果难以再次联系受试者，则会出现潜在问题。对于具有低成本替代指标的罕见暴露情况，作者提出了灵活的两阶段设计，即只有一次接触时间，在此时根据替代指标做出关于全面协变量确定的决定。对受试者进行筛查，直到为全面数据收集选定了所需数量的病例和对照。本文介绍了优化该设计的成本/效率的策略以及相应软件。该设计应用于职业和遗传流行病学的两个实例。通过确保最罕见疾病 - 协变量组合的最小数量，我们比标准两阶段研究获得了显著的效率提升，同时提高了实际可行性。对于针对具有低成本替代指标的罕见暴露效应进行的针对性研究，灵活的两阶段设计可能是首选设计。
