title: [The case-case-time-control study design].
abstract: Although the 'self-matched case-only studies' (such as the case-cross-over or self-controlled case-series method) can control the time-invariant confounders (measured or unmeasured) through design of the study, however, they can not control those confounders that vary with time. A bidirectional case-crossover design can be used to adjust the exposure-time trends. In the areas of pharmaco-epidemiology, illness often influence the future use of medications, making a bidirectional study design problematic. Suissa's case-time-control design combines the case-crossover and the case-control design which could adjust for exposure-trend bias, but the control group may reintroduce selection bias, if the matching does not go well. We propose a "case-case-time-control" design which is an extension of the case-time-control design. However, rather than using a sample of external controls, we choose those future cases as controls for current cases to counter the bias that arising from temporal trends caused by exposure to the target of interest. In the end of this article we will discuss the strength and limitations of this design based on an applied example.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhuo
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China. Email: siyan-zhan@bjmu.edu.cn.
authors.forename: Siyan
authors.initials: S
authors.lastname: Zhan
mesh_terms: D015982:Bias; D016022:Case-Control Studies; D018592:Cross-Over Studies; D006801:Humans; D012107:Research Design; D013997:Time Factors