Analytical Epidemiology.ppt epidemiology and its principles in health

health

1. 11
Analytical epidemiology
•Second major type of epidemiological studies
•Subject of interest is individual
•The object is not to formulate, but to test the
hypothesis (causal hypothesis)causal hypothesis).
•Analytical studies comprise of
–Case control study
–Cohort study

2. 22
Case- Control Studies (Retrospective study)Case- Control Studies (Retrospective study)
•A common A common first approachfirst approach
•Increasingly used to know the causes of diseases, Increasingly used to know the causes of diseases,
especially rare diseasesespecially rare diseases
• 3 distinct Features are…3 distinct Features are…
–Both exposure and outcome have occurred
before the onset of the study
–Study proceeds backwards, from effect to
cause
–Use a control or comparison group to
support or refute an inference

3. 33
Design of a case-control studyDesign of a case-control study
Population
Cases
Controls
Exposed
Not exposed
Exposed
Not exposed
Time
Direction of enquiry

4. 44
Basic steps:
4 steps:
1.Selection of cases and controls
2.Matching
3.Measurement of exposure
4.Analysis and interpretation

5. 55
•Selection of cases and controls.
Selection of cases
A)Definition of a case:
•Diagnostic criteria.
•Eligibility criteria.
B) Source of cases
•Hospital
•General population.
Selection of controls
Source of controls:
Hospitals
Relatives
Neighbors
General population

6. 66
How many controls needed ?
Depends on----
No. of cases available,
When large study is contemplated,
The cost to select cases & controls is equal ----
equal no. of cases & control (1:1)
If the study is small (< 50) ---- 2, 3, or 4 can be selected.

7. 77
•Some investigators select cases from one source
and control from another source ---
to avoid “Selection Bias”.
One or more C-C studies in different geographical
areas.
Consistency in results ---- increase in validity.

8. 88
2. Matching2. Matching
•Definition:Definition:
the process by which we select controls in such
a way that they are similar to cases with regard
to certain pertinent selected variables, which are
known to influence the out come of disease and
which, if not adequately matched for
comparability, could distort or confound the
results.

9. 99
•Confounding factor:Confounding factor:
–One which is associated both with exposure
and disease; and is distributed unequally in
study and control groups.
–Although associated with ‘exposure’ under
investigation, is itself independently of any such
association, a “risk factor” for the disease.

10. 1010
•Eg:
•Role of alcohol in the etiology of esophageal
cancer
•Smoking is a confounding factor
•The effects of alcohol consumption can be
determined only if the influence of smoking is
neutralized by matching.

11. 1111
•Methods of matchingMethods of matching
–Group matching
–Matching by pairs
•Over matchingOver matching
–Difficult to find controls
–Reduced odds ratio

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3. Measurement of exposure3. Measurement of exposure
•Define and set the criteria for exposureDefine and set the criteria for exposure
•Information about exposure should be obtained in Information about exposure should be obtained in
the same manner for cases and controls.the same manner for cases and controls.
•Exposure can be measured byExposure can be measured by
–Interviews
–Questionnaires
–By studying past records
–Examinations
•Bias/ systematic error should be avoided while Bias/ systematic error should be avoided while
measuring the exposuremeasuring the exposure

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4. Analysis4. Analysis
•Involves two steps
1.Exposure rates among cases and controls
2.Estimation of disease risk associated with
exposure (odds ratio).
Cases with lung
cancer
controls with our
lung cancer
Smokers
<5 cigr/d
33
a
55
b
Non smokers 2
c
27
d
Total a + c=35 b + d= 82
Exposure rates:
Cases =a/a + c= 33/35=94.2%
Controls = b/ b + d=55/82= 67%

14. 1414
Estimation of risk.
•An index known as Relative risk. (RR ) or risk
ratio.
•RR is defined as the ratio between the incidence
of disease among exposed persons and
incidence among non exposed.
•Relative risk= incidence among exposed
incidence among non exposed
a/a + c
b/ b + d

15. 1515
Odds ratio (cross product ratio)Odds ratio (cross product ratio)
•It is a key parameter in the analysis of case
control studies
•A measure of the strength of the association
between risk factor and outcome
•Derivation of odds ratio is based on 3
assumptions
•Disease under investigation is a rare one
•Cases are representative of those with disease
•Controls are representative of those without
disease

16. 1616
CasesCases ControlsControls
SmokersSmokers 3333
(a)(a)
5555
(b)(b)
Non smokersNon smokers 22
( c )( c )
2727
(d)(d)
Total Total 3535
(a+c)(a+c)
8282
(b+d)(b+d)
Odds ratio = ad/bc = 33 X27/ 55X2 = 8.1
Smokers have a risk of having lung cancer
8.1 times that of non smokers

17. 1717
•Bias :
•is any systematic error in the
determination of the association
between the exposure and disease.
•It reflects some type of non-
comparability between the study and
the control group.

18. 1818
Bias in case control studiesBias in case control studies
•Bias due to confounding
•Memory or recall bias
•Selection bias:
•Berkesonian bias: different rates of admission to
• hospitals for people of different diseases.
•Interviewer bias

19. 1919
ADVANTAGES ADVANTAGES
•Relatively easy to carry out.
•Rapid and inexpensive (compared with cohort studies).
•Require comparatively few subjects.
•suitable to investigate rare diseases or diseases
about which little is known.
•No risk to subjects.
•Allows the study of several different aetiological factors (e.g.,
smoking, physical activity and personality characteristics in
myocardial infarction).
•Risk factors can be identified. Rational prevention and control
programmes can be established.
•No attrition problems, because case control studies do not
require follow-up of individuals into the future.
•Ethical problems minimal.

20. 2020
DisadvantagesDisadvantages
•High chances for bias.
•Validation of information obtained is difficult or sometimes
impossible.
•Selection of an appropriate control group may be difficult.
•We cannot measure incidence, and can only estimate the
odds ratio but not relative risk.
•Difficult to establish temporality of cause and effect.
•Not suited to the evaluation of therapy or prophylaxis of a
disease.
•Another major concern is the representative ness of cases
and controls

21. 2121
Cohort study
•Cohort is defined as a group of people who share a
common characteristic or experience with in a defined
time period ( ex. Age, occupation exposure, to a drug or
vaccine, pregnancy, insured person).
•Usually undertaken to obtain additional evidence to
refute or support the existence of an association
between suspected cause and disease
•Other names
–Incidence study
–Forward looking study
–Longitudinal study
–Prospective study
•However, the most widely used and appropriate term is
cohort study

22. 2222
Distinguishing features of cohort study,
–Cohorts are identified prior to the
appearance of disease under
investigation.
–Study groups so defined are observed
over a period of time to determine
frequency of disease among them.
–Study proceeds forward from cause to
effect.

23. 2323
Indication for cohort study.
–When there is good association between
exposure and disease.
–When exposure is rare, but incidence of
disease high among exposed ex:
exposure to x ray
–Attrition of study population is minimized.
–Ample funds are available.

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Frame work of cohort study
Cohort Disease Total
Yes No
Exposed to putative
etiologic factor
a b a + b
Not exposed to putative
etiologic factor c d c + d

25. 2525
Types of cohort studies
1.) Prospective cohort studies.
•These studies begin in the present and continue into
future.
•Out come has not yet occurred.
2.) Retrospective cohort studies
•Out come have all occurred before start of the
investigation.
•Investigator goes back in time and selects his study
groups from past medical, employment records.
3.) combination cohort studies

26. 2626
Elements of cohort study:
1.) Selection of study subjects
2.) Obtaining data on exposure
3.) Selection of comparison
4.) Follow up
5.) Analysis

27. 2727
1.)Selection of study subjects
•Cohorts can be selected from
–General population
–Special groups
•Select groups (eg. Doctors, lawyers,
teachers, etc.)
•Exposure groups

28. 2828
2.) Obtaining data on exposure2.) Obtaining data on exposure
•Information can be obtained from
–Cohorts
–Review of records
–Medical examination or special tests
–Environmental surveys
•Information about exposure should facilitate classification of
cohort members
–According to whether or not they were exposed
–According to the degree of exposure.

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3.) Selection of comparison groups:
•Internal comparison
•External comparison
•Comparison with general population rates.
•
4.) Follow up
•At the start of the study out come should be
determined (morbidity, mortality) to asses this
•Periodic medical examination
•Reviewing physician and hospital records
•Routine surveillance of death records
•Mailed questionnaire, telephone calls etc.

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5.) Analysis Analysis
•Data is analyzed interms of
i.Incidence rates of outcome among
exposed and non-exposed.
ii. Estimation of risk
•Relative risk
•Attributable risk

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i.)Incidence ratesi.)Incidence rates
•Incidence can be measured Incidence can be measured
directlydirectly
•Incidence rate among smokers = Incidence rate among smokers =
70/7000 = 10 per thousand70/7000 = 10 per thousand
•Incidence rate among non-Incidence rate among non-
smokers= 3/3000 = 1 smokers= 3/3000 = 1
per 1000per 1000
P < 0.001P < 0.001
CigarCigar
ette ette
smoksmok
inging
Lung Lung
cancecance
rr
No No
lung lung
cancecance
rr
Total Total
YesYes 7070
aa
69306930
bb
70007000
a+ba+b
NoNo 33
cc
29972997
dd
30003000
c+dc+d

32. 3232
Relative riskRelative risk
•The ratio of incidenceThe ratio of incidence
among exposed and among exposed and
incidence among incidence among
non-exposednon-exposed
•Also called ‘risk ratio’Also called ‘risk ratio’
•RR=RR=
•What does it mean ???What does it mean ???
•RR is the direct measure of RR is the direct measure of
strength of association between strength of association between
suspected cause and effect suspected cause and effect
CigarettCigarett
e e
smokinsmokin
gg
Lung Lung
cancecance
rr
No No
lung lung
cancecance
rr
Total Total
YesYes 7070
aa
69306930
bb
70007000
a+ba+b
NoNo 33
cc
29972997
dd
30003000
c+dc+dIncidence among exposed
Incidence among non-
exposed
=10/1 = 10

33. 3333
Attributable riskAttributable risk
•The difference in incidence rates between exposed
and non-exposed groups
•Also called risk difference
•AR =
•What does it mean???
•It indicates to what extent disease can be attributed
to the exposure
•Suggests the amount of disease that might be
eliminated if the factor could be controlled
Incident rate among exposed – incidence rate among non-exposed
Incident rate among exposed
X 100

34. 3434
Relative riskAttributable risk
• Important in etiologic
enquires
•It doesn't reflects the
potential public health
importance.
•It reflects the potential
public health
importance.
•Gives better idea of
successful preventive
public health program

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Advantages of cohort studiesAdvantages of cohort studies
•Allow the possibility of measuring directly
the relative risk of developing the condition for those
who have the characteristic, compared to those who do
not.
•Allows for a conclusion of cause-effect relationship
(a necessary, but not sufficient, condition).
•Because the presence or absence of the risk factor is
recorded before the disease occurs, there is no chance
of bias being introduced due to awareness of being sick
as encountered in case-control studies.

36. 3636
•There is also less chance of encountering the problem
of selective survival or selective recall, although
selection bias can still occur because some subjects who
contracted the disease will have been eliminated from
consideration at the start of the study.
•Cohort studies are capable of identifying other diseases
that may be related to the same risk factor.
•Unlike case-control studies, cohort studies provide the
possibility of estimating attributable risks, thus indicating
the absolute magnitude of disease attributable to the risk
factor.

37. 3737
Disadvantages of cohort studiesDisadvantages of cohort studies
•Not always feasible.
•Relatively inefficient for studying rare conditions.
•They are very costly in time, personnel, space and patient
follow-up.
•Sample sizes required for cohort studies are extremely large,
especially for infrequent conditions; it is usually difficult to find and
manage samples of this size.
•The most serious problem is that of attrition, which can affect the
validity of the conclusion, if it renders the samples less
representative, or if the people who become unavailable are
different from those actually followed up. The higher the proportion
lost (say beyond 10-15%) the more serious the potential bias.

38. 3838
•There may also be attrition among
investigators who may lose interest, leave for
another job, or become involved in another
project.
•Over a long period, many changes may occur
in the
environment, among individuals or in the type
of
intervention, and these may confuse the issue
of
association and attributable risk.

39. 3939
Case control studyCase control study
•Proceeds from effect to
cause
•Starts with the disease
•Tests whether the
suspected
cause occurs more
frequently
in those with the disease
than
among those without the
disease.
•Usually the first approach to
the testing of a hypothesis,
but
also useful for exploratory
studies
•Involves fewer number of
subjects
Cohort studyCohort study
Proceeds from "cause to
effect".
Starts with people
exposed to risk factor or
suspected cause.
Tests whether disease
occurs more frequently
in those exposed, than in
those not similarly
exposed.
Reserved for testing of
precisely formulated
hypothesis
Involves larger number
of subjects

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Case control studyCase control study
•Yields relatively quick Yields relatively quick
resultsresults
•Suitable for the study Suitable for the study
of rareof rare
diseasesdiseases
•Generally yields only Generally yields only
estimateestimate
of RR (odds ratio)of RR (odds ratio)
•Cannot yield Cannot yield
information aboutinformation about
diseases other than diseases other than
thatthat
selected for studyselected for study
•Relatively inexpensiveRelatively inexpensive
Cohort studyCohort study
Long follow-up period Long follow-up period
often needed, involving often needed, involving
delayed results.delayed results.
Inappropriate when the Inappropriate when the
disease or exposure disease or exposure
under investigation is under investigation is
rare.rare.
Yields incidence rates, Yields incidence rates,
RR as well as AR.RR as well as AR.
Can yield information Can yield information
about more than one about more than one
disease outcome.disease outcome.
Expensive.Expensive.

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Nested case-control studiesNested case-control studies
•A combined design of case-control and cohort studies
•Cases and controls are selected from the study
population of a cohort study
•Less expensive and less time consuming than a
cohort study, yet yields the findings with nearly the
same level of precision
•Reduced bias and temporal ambiguity compared to a
case-control study
•Mostly used in occupational epidemiology