Schneeweiss S, Stürmer T, Maclure M
Department of Medical Informatics, Biometry and Epidemiology (IBE), Pharmacoepidemiology Group, University of Munich, Germany.
Pharmacoepidemiol Drug Saf. 1997 Oct;6 Suppl 3:S51-9. doi: 10.1002/(SICI)1099-1557(199710)6:3+<S51::AID-PDS301>3.0.CO;2-S.
Standard cohort and case-control designs are suited to the study of cumulative effects of chronic exposures, but they are prone to confounding by indication. Case-crossover and case-time-control studies are especially useful for studying intermittent exposures with transient effects, and are less susceptible to confounding by indication. Each design has its strengths and weaknesses. Despite the increasing availability of automated databases, cohort studies are usually time consuming and expensive, and therefore not preferred for time-critical decisions. In case-control studies, the selection of appropriate controls can be difficult and time consuming, and sometimes impractical when the exposure is rare. Case-crossover studies use the exposure history of each case as his or her own control to examine the effect of transient exposures on acute events. It further allows to study the time relationship of immediate effects to the exposure. This design eliminates between-person confounding by constant characteristics, including chronic indications. Because exposure data for the case and control periods are provided by the same person, the problems of differential recall may be reduced in many but not all case-crossover studies. Bias can result from temporal changes in prescribing or within-person confounding, including transient indication or changes in disease severity. The case-time-control design is an elaboration of the case-crossover design, which uses exposure history data from a traditional control group to estimate and adjust for the bias from temporal changes in prescribing. This paper will present a structured decision table of when to use which design in pharmacoepidemiologic research. In conclusion, case-crossover and case-time-control studies are the designs of choice when separating acute effects from chronic effects of transient exposures and if confounding by indication is an outstanding problem.
标准队列研究和病例对照研究适用于慢性暴露累积效应的研究，但容易受到指征性混杂因素的影响。病例交叉研究和病例-时间对照研究对于研究具有短暂效应的间歇性暴露特别有用，并且较不易受到指征性混杂因素的影响。每种设计都有其优缺点。尽管自动化数据库越来越容易获取，但队列研究通常耗时且昂贵，因此对于时间紧迫的决策并非首选。在病例对照研究中，选择合适的对照可能困难且耗时，当暴露罕见时有时甚至不切实际。病例交叉研究将每个病例的暴露史作为其自身对照，以检验短暂暴露对急性事件的影响。它还允许研究即时效应与暴露之间的时间关系。这种设计消除了包括慢性指征在内的个体恒定特征所导致的个体间混杂。由于病例期和对照期的暴露数据由同一人提供，在许多但并非所有病例交叉研究中，差异回忆问题可能会减少。偏倚可能源于处方的时间变化或个体内混杂，包括短暂指征或疾病严重程度的变化。病例-时间对照设计是病例交叉设计的一种改进形式，它使用来自传统对照组的暴露史数据来估计并调整因处方时间变化导致的偏倚。本文将给出一个结构化决策表，说明在药物流行病学研究中何时使用哪种设计。总之，当区分短暂暴露的急性效应与慢性效应且指征性混杂是一个突出问题时，病例交叉研究和病例-时间对照研究是首选设计。
