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Analytical Studies
Case – Control StudiesBy
Dr. Sameh Zaytoun(MBBch, DPH, DM, FRCP(Manch), DTM&H(UK) ,Dr.PH)
University of Alexandria - EgyptConsultant of Preventive MedicineAl- Hada Armed Forces Hospital
Analytical Studies Cohort
Natural History
Case – Control
Risk Factors
(Exposure)Disease
(Outcome)
Retrospective
Prospective
Case – Control StudiesMost commonly used Epidemiologic study
design despite numerous potential biasesMost suitable for diseases for which
medical care is usually soughtMost suitable for diseases with relatively
short period between appearance of symptoms and time of diagnosis.
Case – Control Studies
More efficient than the equivalent Cohort studies
Makes it possible to study Rare Diseases
Case – Control StudiesDesign in Words: Select representative persons (Cases) with the study
Outcome Select comparable (Controls) without the study
Outcome Look historically in both groups for the Exposure Compare Odds of exposure in cases and in controls
(generate Odds Ratio to see if the Exposure is related to the development of the Outcome).
Interpretation of Case – Control study
All else being equal, if the Odds of Exposure differ between the Cases and the Controls by more than chance variation, the Exposure is said to be related to the Outcome
Ideal Design of a Case – Control Studies
Reference Population
Cases Controls A like except for case status
Exposure
PresentExposure
AbsentExposure
Absent
Identify all Exposure without Bias
Exposure Present
Analysis of Case – Control Ideal Design
Outcome +ve
Outcome -ve
Factor +ve A B
Factor -ve C D
Odds A / C B / D
A / C
B / DOdds Ratio =
Strength of Association
Outcome Present
Outcome Absent
Factor Present
Factor Absent
Factor Present
Factor Absent
Rare Disease Assumption:Odds ratio ~ = Relative risk
When the disease is Rare, the exposure Odds Ratio from a case – Control study is approximately equal to the Relative Risk that would be obtained from the equivalent Cohort study.
Issues to be in concern in a Case – Control study design: Selection of Cases Selection of Controls **** Ascertainment of Exposure
Selection of Cases:
• Often selected among persons seeking medical care
• A uniform diagnostic criteria to define a case is required
• Incident cases (versus prevalent cases) almost always preferable.
Prevalent Cases:Over representation of cases with long
disease duration (those who did not die and those who did not cured)
Exposure / Disease relation may actually be an Exposure / Duration relation
Subjects less likely to remember ExposuresMore difficult to establish timing of
Exposures relative to the disease onset.
Incident Cases:
Usually based on time of DiagnosisFor some diseases, onset may be long
before diagnosisReference period for measurement of
Exposure should precede the disease onset (Exposure always precedes the onset of disease i.e. there is a temporal relation).
Selection of Controls:Appropriate Source:Hospital ControlsNeighborhood ControlsFriendship ControlsCommunity ControlsMultiple Control groupsInappropriate Source:VolunteersGroups Biased due to Exposure (e.g. GIT patients as
controls in a study linking Coffee and Pancreatic Carcinoma).
Selection of Controls: Most difficult and controversial issue in design
of a Case – control study The Controls should be an unbiased sample of
the study base Study base: source population from which
cases arise during the time period when they are eligible to become cases.
Cases and controls idealy are to be taken from the same population pool.
Selection of Controls:
Controls are not selected because they have characteristic similar to the cases
Controls are selected because they would have become cases if they had gotten the disease.
Population – based Controls:If cases consist of all individuals developing
the disease in a defined population, the best control group is a random sample of individuals from the same source population who have not developed the disease.
It also could be taken through a random digit dialing or through population registries (e.g. census, health insurance….etc).
Clinical Controls:Patients seeking care for conditions other
than the disease of interest at the facilities where the cases are identified
Best to choose patients with a variety of diseases
Patients with diseases thought to be related to the Exposure of interest should be excluded.
Clinical Controls:
Certain Exposures (e.g smoking, obesity) are over represented among hospital Controls because these Exposures are associated with many different diseases
Neighborhood Controls: Assumes that neighbors of cases would
seek care at the same medical facility as the cases.
May not be possible to examine risk factors that are closely linked to Socio-economic or Environmental exposures, because cases and controls are too similar.
Selection of Controls:
In some situations, no single Control group is obviously the best
May include two or more control groups (e.g. population controls and clinical controls).
Obtaining Exposure information:
Interview Existing records Physical measurements Laboratory tests
Obtaining Exposure information: Methods must be comparable in Cases and in
Controls Observers should be “blind” to Case / Control
status Appropriate definition of Reference period is
essential How define Reference period for Controls?
Obtaining Exposure information:Definition of Reference period should be
based on knowledge about the disease in question
For chronic disease with long latent period, reference period may be very long
For acute disease, reference period may be a short period immediately preceding the diagnosis.
Advantages of Case – Control studies:Fewer subjects required than the Cohort
studiesLess expensive and faster than Cohort
studiesPossible to study Rare diseasesMore than one Risk factor can be studied at
the same time.
Disadvantages of Case – Control studies:• The events of interest have already occurred when
the study is done• Exposure information may not be available or may
not be accurate• Prone to recall bias• Prone to selection bias• Relative risk (Risk Ratio) of the disease can not be
estimated (it could only estimate the Odds ratio).
Preventive Medicine Department 2007