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Transcript of Instructor Resource Chapter 11 Copyright © Scott B. Patten, 2015. Permission granted for classroom...
Instructor Resource
Chapter 11
Copyright © Scott B. Patten, 2015.
Permission granted for classroom use with Epidemiology for Canadian Students: Principles, Methods & Critical Appraisal (Edmonton: Brush Education Inc. www.brusheducation.ca).
Chapter 11. Case-control studies
Objectives
• Define case-control studies.• Explain how to interpret measures of association calculated
from case-control data.• Describe recall bias.• Describe the rare disease assumption.• Distinguish between induction and latency periods for
disease, and describe the dynamic of component causes of disease.• Define primary, secondary, and tertiary prevention.• List strengths and weaknesses of case-control studies.
What is a case-control study?• It is a type of analytic study: it usually has analytic
goals.• Participants are selected based on their disease
status.• Participants include:• cases (who have the disease under investigation)• controls (who do not)
• Exposure is assessed retrospectively.
2 x 2 table for case-control studies
Cases Controls
Exposed a b
Nonexposed c d
Total ncases ncontrols
2 x 2 table for case-control studies(continued)
• You can’t calculate prevalence from this 2 x 2 table because there is no expectation that the estimated proportion with disease would reflect the population prevalence.
A measure of association for case-control studies
Odds R atio=
𝑎𝑐𝑏𝑑
=𝑎𝑑𝑏𝑐
Odds ratios
• Recall that a prevalence odds ratio could be calculated from cross-sectional data.• The formula was the same.• However, as the case-control design usually has
analytical goals, incidence is of more interest.• Case-control studies rarely use prevalent cases.• When the cases are incident cases, the estimated
odds ratio is an incidence odds ratio.
Advantages of case-control studies• The main advantage of the case-control design is its
efficiency. • The design is efficient because selection of cases
can be accomplished flexibly and the control group is usually only a small subset of the analogous group in the general population.• Therefore, a relatively small investment of research
resources can produce a precise estimate.
Case-control studies
• Links to examples:• http://www.ncbi.nlm.nih.gov/pubmed/8059766• http://www.ncbi.nlm.nih.gov/pubmed/15364185• http://www.ncbi.nlm.nih.gov/pubmed/23164221• http://www.ncbi.nlm.nih.gov/pubmed/25208536• http://www.ncbi.nlm.nih.gov/pubmed/21033532
Selection bias in case-control studies• Selection bias is a major methodological concern
for case-control studies.• Selection bias results if selection of cases and
controls depends on exposure in some way that is not equivalent between the 2 groups.• It is easiest to be confident that selection bias has
not occurred if the selection of cases and controls does not depend in any way on exposure.
Berkson’s bias
• This is bias that arises when selection of cases and controls occurs in a hospital setting.• The probability of hospitalization is often related to
exposure in a way that differs in cases and controls.
Misclassification bias in case-control studies• Since the target of estimation is a more complex
parameter (an odds ratio rather than simply odds, a frequency, or a rate), this is a more difficult issue than it was in prevalence or incidence studies.• The problem becomes easier if you consider the
numerator (odds of exposure in cases) and the denominator (odds of exposure in controls) separately.• If the numerator is inflated, the estimate of the odds
ratio will be too high. • If the denominator is inflated, the estimate of the
odds ratio will be too low.
Nondifferential misclassification of exposure• Exposure assessment is prone to error in case-
control studies because it is retrospective.• The measure of exposure can have low sensitivity
and/or low specificity.• Low sensitivity produces false negatives.• Low specificity produces false positives.• If the error rates are the same in cases and
controls, the misclassification is nondifferential.
Differential misclassification of exposure• If the error rates in classification of exposure are
different in the cases and controls, the misclassification is differential.• A classical type of differential misclassification bias
in case-control studies is recall bias.
Recall bias
• Imagine a study of drug exposures during pregnancy (exposure) as a risk factor for birth defects (outcome).• Since mothers of babies with birth defects are likely
to reflect more deeply about their pregnancy, they may have more accurate recall of past drug exposures. • What effect would this have on the odds ratio (OR)?
Recall bias (continued)
• The sensitivity for exposure in the controls is lower than in the cases.• Therefore, the odds of exposure in the controls
(denominator of the OR) will be too small.• This will lead to an overestimation of the OR.
Nondifferential misclassification bias• What if the sensitivity for assessment of exposure
was the same (nondifferential) in cases and controls.• The direction of bias is towards the null value for
the OR (which is 1).
The rare disease assumption• Imagine the classic 2 x 2 table.• Note that when a disease is rare, a and b are small
and the ratio of the 2 odds approximates the ratio of the analogous 2 proportions.
Disease No Disease
Exposed a b
Nonexposed c d
The rare disease assumption (continued)• When the disease is rare….
abis approximately
aa+b
Disease No Disease
Exposed a b
Nonexposed c d
The rare disease assumption (continued)• (and) When the disease is rare….
cdis approximately
cc+d
Disease No Disease
Exposed a b
Nonexposed c d
Induction period
• This is the period of time between exposure to a risk factor and the initiation of a disease mechanism.• An advantage of the case-control design is that it
can assess associations characterized by long induction periods.
Latency period
• Latent means “hidden.”• A latency period is the time between the initiation
of a disease and its emergence as a clinically evident entity.
Primary, secondary, and tertiary prevention
• Primary prevention: preventing the occurrence of disease by eliminating a risk factor or its effects (occurs in the induction phase).• Secondary prevention: improving outcomes
through earlier detection (in the latency phase).• Tertiary prevention: diminishing the impact of a
disease (after the disease has become a clinical entity).
Strengths of the case-control study design• efficiency• fit with rare diseases• fit with long induction and latency periods• ability to examine multiple exposures
Weaknesses of the case-control study design• vulnerable to selection and misclassification bias• not a good fit for rare exposures• limited to estimating odds ratios (cannot, for
example, estimate incidence.• temporality issues: in studies of prevalent cases,
the timing of exposure and disease may be unclear
End