Case-Control Studies
(Retrospective Studies)
What is a cohort?
Cohort
A group of individuals who share a common
characteristic, e.g. all of the individuals born
in one year (a birth cohort) or a group of
individuals entered in a prospective study or
clinical trial.
The term always carries a connotation that:
individuals are observed over a period of time
and that summary statistics describe the
experience of real individuals rather than
mathematical abstractions, e.g., a cohort
study or a cohort life table.
Design of a Case-Control Study
WERE
WERE NOT
WERE
WERE NOT
EXPOSED
EXPOSED
EXPOSED
EXPOSED
HAVE THE DISEASE
DO NOT HAVE THE DISEASE
“CASES”
“CONTROLS”
When is a Case-Control
Study Warranted?
• Useful as a first step when searching
for an adverse health outcome
• Useful when disease being
investigated is rare
Retrospective Studies
Disadvantages
•
•
•
•
•
information not easily available
difficult to validate
quality of survey
bias in selection
possible misconception of factors
causing disease
• recall may be flawed
Retrospective Studies
Advantages
•
•
•
•
inexpensive
easy
requires fewer subjects
useful for rate of disease or diseases
with long latency periods
• can check for more than one risk
factor
• useful for drug induced illness
Selection of Cases and Controls
• Variety of sources
avoid bias
• Choose incidence or prevalent
cases?
• Controls must represent general
population
can be hospitalized or non-hospitalized
Problems in Control Selection
• Controls must be carefully selected
otherwise, results may be confounded
• Coffee and pancreatic cancer study
Apparent dose-response relationship between
coffee consumption and pancreatic cancer
• Cases = confirmed diagnosis of pancreatic cancer
• Controls = from all patients hospitalized at same
time and by same attending physicians as cases
Difficult to know if disease caused by coffee
drinking or some factor closely related to
coffee drinking (confounding factor)
Problems in Control Selection (cont.)
• Coffee and pancreatic cancer study (cont.)
One such confounding factor was cigarette
smoking --- most smokers are coffee drinkers
--- and cigarette smoking is a known risk
factor for pancreatic cancer
To rule out effect of smoking, the data was
stratified for smoking history and reanalyzed
• Current smokers
• Never smokers
and the dose-response relationship with
coffee consumption held for both groups
Problems in Control Selection (cont.)
• Coffee and pancreatic cancer study (cont.)
Objective in control group is to have level of
coffee consumption approximate that in
general population --- and thus, that cases
demonstrate excessive coffee consumption
Problem was that attending physicians
referring both cases and controls were
gastroenterologists
• Controls may have reduced coffee consumption
because of their gastrointestinal problems, e.g.,
esophagitis or peptic ulcer disease
• Controls coffee intake may be abnormally low
compared to general population
Problems in Control Selection (cont.)
• Coffee and pancreatic cancer study (cont.)
 Therefore, the dose-response relationship
differences between cases and controls may
not be due to cases drinking more coffee, but
rather, controls drinking less coffee than
expected
• Conclusion: when difference in exposure
is observed between cases and controls,
controls must not have a level of
exposure that is significantly higher or
lower than the general population
Matching
• Concern that cases and controls may
differ in characteristics or exposures
other than that observed in the study
• To overcome this problem, we can
match cases in controls in regard to
potential factors of concern
• Matching selects controls that are
similar to cases in characteristics
such as age, race sex, socioeconomic
status, occupation, etc.
Matching
• Group matching (frequency matching)
proportion of controls with a given
characteristic (variable) is identical to
proportion of cases with the same
characteristic
• Individual matching (matched pairs)
for each case, a control is selected who
is similar to the case for a given
variable(s)
Problems with Matching
• Practical problems
attempting to match too many
characteristics (variables)
• Conceptual problems
once controls are matched to cases
according to a given characteristic
(variable), that characteristic can not be
studied, because matching artificially
establishes identical proportions for that
characteristic among cases and controls
Recall (Interview) Problems
• Limitations in recall
• Recall bias
One group (e.g., mothers with child with
birth defect) may clearly remember
(recall) an event (e.g., mild respiratory
infection)
Other group (e.g., mothers with healthy
child) may not recall any such event
Use of Multiple Controls
• Same type
2, 3, or even 4 controls for each case
(i.e., increasing the ratio of matched
controls to cases), increases the power
of the study
• Different types
where there is concern that the controls
may differ in some way from what is
“expected” in the general population