Should we use a case-crossover design?

The first decade of experience with case-crossover studies has shown that t he design applies best if the exposure is intermittent, the effect on risk is immediate and transient, and the outcome is abrupt. However, this design has been used to study single changes in exposure level, gradual effects o n risk, and outcomes with insidious onsets. To estimate relative risk, the exposure frequency during a window just before outcome onset is compared wi th exposure frequencies during control times rather than in control persons . One or more control times are supplied by each of the cases themselves, t o control for confounding by constant characteristics and self-confounding between the trigger's acute and chronic effects. This review of published c ase-crossover studies is designed to help the reader prepare a better resea rch proposal by understanding triggers and deterrents, target person times, alternative study bases, crossover cohorts, induction times, effect and ha zard periods, exposure windows, the exposure opportunity fallacy, a general likelihood formula, and control crossover analysis.