Designs• Case-crossover design

– When investigating an intermittent exposure with immediate and transient effect on risk related to an abrupt outcome

– All cases are incident occurrences of the disease of interest

– Cases at another time (or other times) serve as their own controls

Designs• Case-crossover design

– Developed in 1988 due to concerns about ability to find controls representing the study base for a study of causes of MI peaks in the morning

– Realized could compare each patient’s experience on their MI day with their experience the day before (or multiple control days before)

Designs• Case-crossover design

– Analogous to the experimental cross-over design except that the data are:• Non-experimental• Observed retrospectively

Designs• Case-crossover design

– Publicized in 1997 with media coverage of an analysis showing that car phone calls were associated with increased risk of collision

Designs

Designs• Case-crossover design

– For each case, can sample:• One control time• Multiple control times• Sample of the person-time over a defined period

Designs• Case-crossover design

– Trends in time (e.g., seasonality) are main challenge specific to this design

Case crossover example• Valent et al. A case-crossover study of sleep and childhood injury. Ped 2001;107: E23

• Research question• Does lack of sleep result in a greater number of unintentional childhood

injuries?• Exposure = sleep <10 hours (EXP +) vs. >= 10 hours (EXP -)• Outcome = Childhood unintentional injury

• Study population = 292 children with unintentional injuries• Sleep time data collected for two periods (0-24 hours before injury) and (25-48

hours before injury)• “Case period” = 24 hour period before injury; “Control period” = 25-48 hour period

before injury• Note that each child has both one case and one control period...these two

periods together form a pair• Analysis is done through a matched analysis in which the time periods (case and

control periods) are matched• Four possible scenarios

• a. Case period = (EXP +) and Control period = (EXP +)...”concordant”• b. Case period = (EXP +) and Control period = (EXP -)...”discordant”• c. Case period = (EXP -) and Control period = (EXP +)...”discordant”• d. Case period = (EXP -) and Control period = (EXP -)...”concordant”

• Concordant pairs offer no “information” about the effect of sleep < 10 hours (EXP +) vs. sleep > 10 hours (EXP -)