7.2 - Advanced Case-Control Designs

Nested Case-Control Study: This is a case-control study within a cohort study. At the beginning of the cohort study \((t_0)\) , members of the cohort are assessed for risk factors. Cases and controls are identified subsequently at time \(t_1\). The control group is selected from the risk set (cohort members who do not meet the case definition at \(t_1\).) Typically, the nested case-control study is less than 20% of the parent cohort.

Advantages of nested case-control

  • Efficient – not all members of parent cohort require diagnostic testing
  • Flexible – allows testing of hypotheses not anticipated when the cohort was drawn (at \(t_0\))
  • Reduces selection bias – cases and controls sampled from same population
  • Reduces information bias – risk factor exposure can be assessed with investigator blind to case status

Disadvantages

  • Reduces power (from parent cohort) because of reduced sample size by: 1/(c+1), where c = number of controls per case

Nested case-control studies can be matched, not matched or counter-matched.

Matching cases to controls according to baseline measurements of one or several confounding variables is done to control for the the effect from confounding variables. A counter-matched study, in contrast, is when we matched cases to controls who have a different baseline risk factor exposure level. The counter-matched study design is used to specifically assess the impact of this risk factor; it is especially good for assessing the potential interaction (effect modification!) of the secondary risk factor and the primary risk factor. Counter-matched controls are randomly selected from different strata of risk factor exposure levels in order to maximize variation in risk exposures among the controls. For example, in a study of the risk for bladder cancer from alcohol consumption, you might match cases to controls who smoke different amounts to see if the effect of smoking is only evident at a minimum level of exposure.

Example of a Nested Case-Control Study: Familial, psychiatric, and socioeconomic risk factors for suicide in young people: nested case-control study. In a cohort study of risk factors for suicide, Agerbo et al. (2002), enrolled 496 young people who had committed suicide during 1981-97 in Denmark matched for sex, age, and time to 24,800 controls. Read how they matched each case to a representative random subsample of 50 people born the same year!