6.3 - Comparing & Combining Case-Control and Cohort Studies

Comparison of Cohort and Case-control Studies Section

Comparative Term Cohort Study Case-Control Study
Estimates Can calculate incidence rate, risk, and relative risk Only estimates odds ratio
Causality Potentially greater strength for causal investigations Potentially weaker causal investigation
Cost Expensive Less expensive
Time to complete Long-term study Short-term study
Sample size A large sample size often required, especially for rare outcomes Can be powered with a small sample of cases
Efficient designs Efficient design for rare exposure & multiple outcomes Efficient design for rare diseases & multiple exposures
Recall bias Less potential for recall bias More potential for recall bias
Loss to followup More potential for loss to followup Less potential for loss to followup
The natural course of the disease Yes No

Nested Case-Control Study Design Section

This is a case-control study within a cohort study. At the beginning of the cohort study, (t0), members of the cohort are assessed for risk factors. Cases and controls are identified subsequently at time t1. The control group is selected from the risk set (cohort members who do not meet the case definition at t1.) Typically, the nested case-control study is less than 20% of the parent cohort.

Advantages of nested case-control

  • Efficient – not all members of the parent cohort require diagnostic testing
  • Flexible – allows testing of hypotheses not anticipated when the cohort was drawn (at t0)
  • Reduces selection bias – cases and controls sampled from the same population
  • Reduces information bias – risk factor exposure can be assessed with an 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 effect of 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

Example of a Nested Case-Control Study: Familial, psychiatric, and socioeconomic risk factors for suicide in young people: a 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!

Case-Cohort Study Design Section

A case-cohort study is similar to a nested case-control study in that the cases and non-cases are within a parent cohort; cases and non-cases are identified at time t1, after baseline. In a case-cohort study, the cohort members were assessed for risk factors at any time prior to t1. Non-cases are randomly selected from the parent cohort, forming a subcohort. No matching is performed.

Advantages of Case-Cohort Study:

Similar to nested case-control study design:

  • Efficient– not all members of the parent cohort require diagnostic testing
  • Flexible– allows testing hypotheses not anticipated when the cohort was drawn (t0)
  • Reduces selection bias – cases and non-cases sampled from the same population
  • Reduced information bias – risk factor exposure can be assessed with an investigator blind to case status

Other advantages, as compared to nested case-control study design:

  • The subcohort can be used to study multiple outcomes
  • Risk can be measured at any time up to t1  (e.g. elapsed time from a variable event, such as menopause, or birth)
  • Subcohort can be used to calculate person-time risk

Disadvantages of Case-Cohort Study:

As compared to nested case-control study design  –  Increased potential for information bias because subcohort may have been established after t0 exposure information collected at different times (e.g. potential for sample deterioration)