Case-CrossoverCase-CrossoverStudiesStudies

Case-CrossoverCase-CrossoverStudiesStudies

Analytic Study DesignsCase-crossover study:

• Only subjects (cases) who have experienced the disease of interest are selected.

• Investigator postulates a critical exposure period (“empirical induction period”) for the exposure of interest.

• Presence of the exposure is compared between the critical exposure period and other periods of exposure (e.g. conditional odds ratio).

• Good for studying effects of transienttransient exposures.

Analytic Study Designs

Case-crossover study:

Hypothesizedirrelevant (non-causal)

exposure

Hypothesizedrelevant (causal)

exposure

“Empirical induction period”

Outcomeevent

Compare presence of exposure between hypothesized non-causal (A) and hypothesized causal (B) periods of exposure

(A) (B)

Normal background risk

Analytic Study Designs

Case-crossover study:

• Biased selection of controls (selection bias) is eliminated (assuming matched analysis is conducted) since controls represent the population that produced the cases.

• Since each subject serves as their own control, thus, “fixed” confounders are eliminated.

• However, confounding can occur from factors that vary over time and are associated with the exposure and disease of interest (e.g. smoking).

Analytic Study Designs

Case-crossover study:

• If exposure ascertainment differs between the case and control intervals, information bias may be present.

• Overestimation or underestimation of the empirical induction period results in non-differential misclassification – hence bias towards the null.

Case control vs. case-crossoverFrom the topics listed below, select whether the case-control or case-crossover study design is more appropriate.

Exposure Outcome Case-

control

Case-Crossover

Body mass index Endometrial cancer

Cell phone calls Car accident

Family quarrel Stroke

Playing tennis Osteoarthritis

Cocaine use Myocardial infarction

Case control vs. case-crossoverFrom the topics listed below, select whether the case-control or case-crossover study design is more appropriate.

Exposure Outcome Case-

control

Case-Crossover

Body mass index Endometrial cancer ●

Cell phone calls Car accident ●

Family quarrel Stroke ●

Playing tennis Osteoarthritis ●

Cocaine use Myocardial infarction ●

Review of Recommended ReadingReview of Recommended ReadingTraffic law enforcement and risk of crashesTraffic law enforcement and risk of crashes

Review of Recommended ReadingReview of Recommended ReadingTraffic law enforcement and risk of crashesTraffic law enforcement and risk of crashes

--- Case-crossover study designed to assess effect of prior driving conviction on subsequent risk of fatal vehicle crashes.

--- Identified all drivers involved in fatal crashes between 1988 and 1999 in Ontario, Canada.

--- Matched date of fatal crash to previous driving history records (convictions) in Ontario in 1-month period before (case period) and 13-months before (control period) crash.

--- Most common prior driving conviction was speeding, with crashes and convictions more common in the summer.

--- Explored how long a potential association with prior driving convictions may have persisted.

Discussion Question 1Discussion Question 1

Interpret the results in figure 1 and table 2,

including use of alternate control periods

and among various subgroups.

Do these results support the primary

study hypothesis?

Source: Lancet 2003; 361:2177-2182.

Discussion Question 2Discussion Question 2

Interpret the results in figure 2.

Do the results suggest that the effect

of traffic law enforcement on risk

of crashes persists over time?

Source: Lancet 2003; 361:2177-2182.

Discussion Question 3Discussion Question 3

Which of the following potential sources ofconfounding were essentially eliminated bythe use of the case-crossover design?

●Age ● # prior driving convictions●Gender ● # years as licensed driver●Alcohol use while ● cell phone use while driving

Source: Lancet 2003; 361:2177-2182.

Cross-SectionalCross-SectionalStudiesStudies

Cross-SectionalCross-SectionalStudiesStudies

Cross-Sectional Study

• Both a descriptive and analytic study design.• Snapshot of the health status of populations

at a certain point in time.• For each subject, exposure and disease

outcome are assessed simultaneously (hence also called a “prevalence study/survey”).

• Compare prevalence of disease in persons with and without the exposure of interest(e.g. prevalence ratio – same formula as risk ratio).

Cross-Sectional Study

Advantages:

• Quick, easy, and cheap.

• Can study multiple exposures and disease outcomes simultaneously.

• Good for describing the magnitude and distribution of health problems.

Cross-Sectional Study

Disadvantages:

• Prevalent rather than incident cases of disease are identified – exposures may be associated with survival rather than risk of development of disease.

• “Chicken or egg” dilemma – do not know whether the exposure preceded disease, or was a consequence of disease development.

Cross-Sectional Study

Example:

Hypothesis:

Obesity is a risk factor for knee osteoarthritis

Sample: 100 retirees living at “University Village”

Cross-Sectional Study

Medical exam + X-rays to diagnose osteoarthritis of the knee

Osteoarthritis

+ -40 10

20 30

+

-Ob

esit

y 50

50

Cross-Sectional Study

Prevalence of osteoarthritis among obese subjects: 40/50 = 0.8

Prevalence of osteoarthritis amongnon-obese subjects: 20/50 = 0.4

Prevalence ratio = 0.8/0.4 = 2.0

Cross-Sectional Study

Obese subjects are two times more likely to have osteoarthritis of the kneethan non-obese subjects.

Cross-Sectional Study

What came first?

Obesity or Osteoarthritis

Chicken or egg dilemma