Analytical case-control studies compare exposures in groups with and without a disease. Cases are selected who have the disease, and controls without the disease are matched on characteristics like age and sex. Investigators measure past exposures and compare frequencies between cases and controls. The odds ratio association measure compares the odds of exposure in cases versus controls. Selection bias can occur if cases or controls are not representative, and recall bias can occur if cases remember past exposures differently than controls.

1. Analytical study
designs
ABDIRISAK MOHAMED

2. Analytical studies
 Analytical studies are the second major type of epidemiological studies.
 Focus on individual within population unlike descriptive study which look for the whole
population
 Objective not to formulate hypothesis but to test hypothesis.
 To evaluate an association between exposure and disease.
 Analytical studies focuses on the magnitude of the association between the exposure
and the health problem under the study.

3. Types of analytical studies
 Main types of analytical studies are;
 Case control study
 Cohort study
 Randomized controlled trials
 Non-randomized controlled study e.g. Field trials, community trials

4. Analytic study designs used in epidemiology
Design
Sampling Best to use when:
Association
measure
Cross-sectional Entire study group
Exposure and outcome are common
The relationship is not well
understood
Prevalence
Case-control
Recruit cases of
disease and a
control group
without disease
Outcome/disease is rare (roughly
<10% of the population has the
disease)
Odds ratio
Cohort
Recruit people
who are exposed
to a factor and
those who are not
Exposure is rare
Disease does not have a long latency
period
Closed Cohort --
Relative risk
Open Cohort --
Incidence
Experimental
Randomly assign
people to be
exposed
(treatment group)
or unexposed
(control or placibo
group)
You want to see if an intervention or
drug is more effective than another
alternative
There is not a long latency period for
the outcome
Incidence
Epidemic
Investigation
People exposed Outbreak situation
Attack rate ratio
(RR or OR)

5. 1. Case control study

6. Case control study
 Case control study definitions:
A study that compares two groups of people: those with the
disease or condition under study (cases) and a very similar group
of people who do not have the disease or condition (controls).
(National Institute of Health, USA)
The observational epidemiologic study of persons with the
disease (or other outcome variable) of interest and a suitable
control (comparison/ reference) group of persons without the
disease(Dictionary of Epidemiology: 3rd ed; John M Last. 2000)

7. Definition of key terms
 Case : A person in the population or study group identified as having the
particular disease, health disorder or condition under investigation.
(Dictionary of Epidemiology: 3rd ed; John M Last. 2000)
 Control: Person or persons in a comparison group that differs, in disease
experience (or other health related outcome) in not having the outcome
being studied. (Dictionary of Epidemiology: 3rd ed; John M Last. 2000)
 Bias: Any systematic error in the design, conduct, or analysis of a study that
results in mistaken estimates of the effect of the exposure on disease.
 Confounding: When a measure of the effect of an exposure on risk is
distorted because of the association of exposure with other factors that
influence the outcome. It creates data where it is not possible to separate
the contribution that any single causal factor has made an effect.

8. Confounder
Exposure outcome
(i)Associated with the exposure of interest.
(ii) Related to the outcome of the interest.
(iii) It should not be in the direct chain or link between
the exposure and outcome

9. Features of case control study
A case control study involves two populations –
cases and controls and has three distinct features :
1. Both exposure and outcome have occurred
before the start of the study.
2. The study proceeds backwards from effect to
cause.
3. It uses a control or comparison group to support
or refute an inference.

10. • Six essential elements which developed separately over time in
medical history
• Idea of the case
• Interest in disease aetiology and prevention
• Focus on individual, as opposed to group aetiologies
• Anamnesis or history taking from patients
• Grouping individual cases together into series
• Making comparisons of the differences between groups, in order to elicit
average risk at the level of individual
History of case control studies

11. Examples of case control studies

12. 1. Selection of cases and controls : The investigator selects cases
with the disease and appropriate controls without the disease
2. Matching is the selection of controls so that they are similar to
the cases in specified characteristics.
3. Measurement of exposure : obtains data regarding past
exposure to possible etiologic factors in both groups.
4. Analysis and interpretation: The investigator then compares the
frequency of exposure of the two groups.
1
2
BASIC STEPS OF CASE CONTROL STUDY

14. Selection of cases
 Selection of CASES: Case-control studies are prone to bias and confounding therefore Care must
be taken when choosing cases for the study. By ensuring following:-
 1. Representativeness:
Ideally, cases are a random sample of all cases of interest in the source population (e.g. from
vital data, registry data). More commonly they are a selection of available cases from a medical
care facility. (e.g. from hospitals, clinics). Information: can be collected from cases themselves, or
from a respondent by proxy (relative/ friend), from records or a combination of the above.
2. Method of Selection:
Selection may be from incidence or prevalence case:
 Incident cases are those derived from ongoing-ascertainment of cases over time . Selection of
incident cases is optimal. These should be all newly diagnosed cases over a given period of
time in a defined population.
 Prevalent cases are derived from a cross-sectional survey. Prevalent cases do not include
patients with a short course of disease. So patients who recovered early and those who died
will not be included.

15. Contd. Selection of cases
3.Diagnostic criteria for case studies : Diagnostic criteria regarding diagnosis of
cases, types of cases and stage of disease to be included should be
predefined.
 Ideally, all subjects who have the disease should be classified as “having the
disease” and vice versa
 Practically, the ability to classify individuals into the correct disease status depends on the accuracy of
the tests, among other things
a. Validity is the ability of a test to indicate which individuals have the disease and which do not
-Sensitivity The ability of the test to identify correctly those who have the disease
-Specificity The ability of the test to identify correctly those who do not have the disease
b. Diagnostic bias: to avoid diagnostic bias only true positives cases should be selected.

16. 1
6
Figure 1 : the relationship between a diagnostic test result and occurrence of disease
Disease
present (+)
Disease absent
(-)
Test (+) True positives False positives
Test (-) False negatives True negatives

17. Selection of controls
i. COMPARABLE : the controls should be similar to the cases in all respects other
than having the disease .
ii. REPRESENTATIVE : the controls should be representative of all non-diseased
people in the population from which the cases are selected.
iii. Sources of controls
General population
Relatives/Friends/Neighbours
Hospital controls
iv. Number
o Large study: Cases: Control : 1:1
o Small study: Cases: Control : 1:2, 1:3, 1:4.

18. Sources of controls
Source Advantage Disadvantage
Hospital based Easily identified.
Available for interview.
More willing to cooperate.
Tend to give complete and
accurate information (recall
bias).
Not typical of general population.
Possess more risk factors for disease.
Some diseases may share risk factors with
disease under study. (whom to exclude???)
Berkesonian bias
Population based
(registry cases)
Most representative of the
general population.
Generally healthy.
Time, money, energy.
Opportunity of exposure may not be same
as that of cases. (locn, occu,)
Neighbourhood
controls/ Telephone
exchange random
dialing
Controls and cases similar in
residence.
Easier than sampling the
population.
Non cooperation.
Security issues.
Not representative of general population.
Best friend control/
Sibling control
Accessible, Cooperative.
Similar to cases in most
aspects.
Overmatching.

19. Matching
 Matching: It is the selection of controls so that they are similar to the
cases in specified characteristics. (Epidemiology: An Introductory Text;
Mausner & Bahn, 1985)
 Matching is defined as the process of selecting controls so that they are
similar to cases in certain characteristics such as age, sex, race,
socioeconomic status and occupation. (Epidemiology; Leon Gordis, 2004)
 Matching variables (e.g. age), and matching criteria (e.g. within the same 5
year age group) must be set up in advance.

20. Types of matching
 Controls can be individually matched (most common) or
Frequency matched.
1.Individual matching (Matched pairs): search for one (or
more) controls who have the required matching criteria,
paired (triplet) matching is when there is one (two) control
(s) individually matched to each cases.
2. Group matching (Frequency matching): select a
population of controls such that the overall characteristics
of the case, e.g. if 15% cases are under age 20, 15% of the
controls must be also under age 20. another example If
30% of cases are males of Hindu religion in 60-65 years then
we take 30% of similar controls

21. Bias in Case control Study
 Bias is any systematic error in the design, conduct, or
analysis of a study that results in mistaken estimates
of the effect of the exposure on disease.
 Types of bias in case control studies:
Selection bias
Information bias
Confounding bias

22. Types of bias in case control studies
1. Ascertainment and selection bias arise due to
a. Selective loss to follow-up
b. Incomplete ascertainment of cases (Detection or Diagnostic bias)
c. Inappropriate control group
 2. Information Bias (estimation of exposure) Occurs due to -
a. Imperfect definitions of study variables
b. Flawed data collection procedures.
 information bias leads to Misclassification of disease and exposure. Some of the cases or
controls who were actually exposed will be erroneously classified as unexposed, and some
who were actually not exposed will be erroneously classified as exposed.—this generally
results in an underestimate of the true risk of the disease associated with the exposure.
 Types of Information bias –
 Recall bias (usually in case-control studies): Cases who are aware of their disease
status may be more likely to recall exposures than controls
 Interviewer bias : When interviewer is not blinded (knows) case status of subjects there
is potential for interviewer bias

23. Contd. Types of bias in case control
studies
 3. Confounding: When a measure of the effect of an exposure on risk is
distorted because of the association of exposure with other factors that
influence the outcome.
 It is not possible to separate the contribution that any single causal factor
has made
 Confounding Factor: is one which is associated with both exposure & disease , and is
distributed unequally in study & control groups.
 E.g.: Alcohol & Esophageal Cancer ; confounding factor- smoking

24. Analyses and interpretation of case control study
 On analysis of case control study we find out :-
 Exposure rates: the frequency of exposure to suspected risk factor in cases and
in controls
 Odds ratio : Estimation of disease risk associated with exposure.
 The only valid measure of association for the Case control study is the Odds
Ratio (OR)
 OR = Odds of exposure among cases (disease)
Odds of exposure among controls (non-dis)
 Odds of exposure among cases = a / c
 Odds of exposure among controls = b / d
 Odds ratio: = (a/c)/ (b/d) = ad / bc
 Odds ratio (OR )= 1.0 (implies equal odds of exposure - no effect)

25.  Exposure rates:
 A case control study provides a direct estimation of the
exposure rates (frequency of exposure) to the suspected
factor in disease and non-disease groups.
Exposure rates
 Cases = a/ (a + c) = 33/ 35 = 94.2%
 Controls = b/ (b + d) = 55/82 = 67.0%
 Odds ratio: = (a/c)/ (b/d) = ad / bc
Cases
(lung cancer)
Controls
(without lung cancer)
Smokers 33 (a) 55 (b)
Non Smokers 2 (c) 27 (d)
TOTAL 35 (a + c) 82 (b+d)

26. How to interpret the Odds ratio?
 People who smoke have an 8.1 times higher risk of
developing lung cancer compared to those who do not
smoke.

27. Exercise
 An investigator selected 40 cases of gastric carcinoma and an equal
number of controls matched for age, sex and socioeconomic status. It was
found that among cases 30 had an evidence of H pylori infection and
among controls 15 had an evidence of H pylori infection. Is there an
evidence of association between H pylori infection and gastric carcinoma?
1. Draw the two by two table
2. Find exposure rate in cases
3.Find exposure rate in controls
4. Calculate “Odds Ratio”
5. Interprets the results.

28. Application of case control studies
1. Vaccine effectiveness
2. Evaluation of treatment and program efficacy
3. Evaluation of screening programs
4. Outbreak investigations
5. Demography
6. Genetic epidemiology
7. Occupational epidemiology

29. Advantages
1. Only realistic study design for uncovering etiology in rare diseases
2. Important in understanding new diseases
3. Commonly used in outbreaks investigation
4. Useful if inducing period is long
5. Relatively inexpensive

30. Disadvantages
1. Susceptible to bias if not carefully designed
2. Especially susceptible to exposure misclassification
3. Especially susceptible to recall bias
4. Restricted to single outcome
5. Incidence rates not usually calculate
6. Cannot assess effects of matching variables