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