Applied Epidem

APPLIED EPIDEMIOLOGY
Prepared by
Antonio E. Chan, M.D.

Learning objectives
1. Define epidemiology and outline its

scope
2. Differentiate epidemiology from
clinical epidemiology
3. Describe approaches to establishing
“normality”
4. Describe criteria and measures of
disease occurrence commonly used
in epidemiology
5. Enumerate some routinely available
data use in epidemiology
Learning objectives
1. Understand diagnostic test in relation

to disease
2. Describe the main types of
epidemiological studies
3. Enumerate the advantages and
disadvantages of observational
studies compared with experimental
studies
4. Explain cause of disease
5. Outline the steps necessary to
establish the cause of disease
Learning objectives
 Appreciate the differing approaches

used in epidemiology to compare the
occurrence of disease
2. Outline the role of epidemiology in
describing the natural history of a
disease and prognosis
3. Understand the role of epidemiology
in the prevention and control of
disease through identification of the
causes of disease
4. Relate the different stages of the
development of a disease to the
phases of prevention
What is Epidemiology ?
The study of the distribution and

determinants of health-related
states or events in specified
populations, and the application
of this study to control of health
problems
AIMS OF EPIDEMIOLOGY
 To understand the course of the

disease (natural history of the
disease)
 To identify the causes or risk
factors
 To provide effective measures of
treatment and prevention
Uses of epidemiology
Genetic factors
• Causation Good health Ill health
Environmental factors
(including lifestyle) Death
2. Natural history Good health Subclinical Clinical

changes disease
Recovery
Good health
3. Description of health status

of population ILL
health
Proportion with ill health,
change over time, Time
change with age, etc

Uses of epidemiology
Treatment
Medical care
5. Evaluation of
intervention Good health Ill health
Health promotion
Preventive measures
Public health services
APPLIED EPIDEMIOLOGY
 Clinical epidemiology
 Communicable disease epidemiology
 Environmental and occupational
epidemiology
 Molecular epidemiology
CLINICAL EPIDEMIOLOGY
Definition
is the application of epidemiological
principles and methods to the practice of
clinical medicine
is the science of making predictions about

individual patients by counting clinical events
in similar patients, using scientific methods
for studies of groups of patients to ensure
that the predictions are accurate
CLINICAL EPIDEMIOLOGY
Purpose:
 to develop and apply methods of
clinical observations that will lead to
valid conclusions by avoiding being
misled by systematic error and chance
 to make good decisions in the care of
patients
The Relationship Between
EPIDEMIOLOGY + CLINICAL MEDICINE
Populations Individuals
• Studies/Assessments • Diagnosis
• Prevention • Treatment
• Evaluation • Curing
• Planning • Caring
Clinical Question
Issue Question
Abnormality Is the patient sick or well ?

Diagnosis How accurate are tests used to diagnose disease ?
Frequency How often does a disease occur ?
Risk What factors are associated with an increased risk of disease ?
Prognosis What are the consequences of having a disease ?
Treatment How does treatment change the course of disease ?
Prevention Does an intervention on well people keep disease from arising
Does early detection and treatment improve the course of
disease ?
Cause What conditions lead to disease ? What are the pathogenetic
mechanisms of disease
Cost How much will care for an illness cost ?
Sources of data useful for
epidemiology studies
 Data on vital events – birth and death

 Morbidity or disease statistics
 Data on physiologic and or pathologic
condition
 Statistics on health resources and
services
 Statistics pertaining to the
environment
 Demographic data
 Socio-cultural data
Measuring Health and Disease
Clinical question: Is the patient sick or well?
Health is defined as “a state of

complete physical, mental, and
social well-being and not merely the
absence of disease or infirmity.”
Epidemiologist’s definition of health

states
“disease present” or “disease
absent”
Measuring Health and
Disease
Clinical question: Is the patient sick or well?
Diagnostic tests
qualitative diagnostic test
quantitative diagnostic test
Normal (Gaussian) distribution
method
Percentile method
Therapeutic method
Predictive value method
Diagnostic criteria are usually based on

symptoms, signs and test results
1. Hepatitis presence of antibodies in the blood

2. Asbestosis - symptoms and signs of specific
changes
in lung function,
- radiographic demonstration of
fibrosis of
the lung tissue or pleural thickening
and
The Jones Criteria (revised) for Guidance in the
Diagnosis of Acute Rheumatic Fever
A high probability of rheumatic fever is indicated by the presence of
two major or one major and two minor, manifestations, if supported
by evidence of a preceding Group A streptococcal infection
Major Manifestations Minor Manifestations

Carditis Clinical:
Polyarthritis fever
Chorea athralgia (joint pains)
Erythema marginatum previous rheumatic
fever or
Subcutaneous nodules rheumatic heart
disease
Laboratory:
Acute phase
reactants:
Abnormal ESR,
CRP,
leukocytosis
WHO CASE-DEFINITION FOR AIDS
The presence of disseminated Kaposis sarcoma or

cryptococcal meningitis
or
Two major signs in association with at least one minor sign
MAJOR SIGNS MINOR SIGNS
Weight loss > 10% Persistent cough > 1

month
Fever > 1 month General pruritic dermatitis
Chronic diarrhea > 1 month Recurrent herpes zoster
General
lymphadenopathy
Chronic herpes simplex
Oral candidiasis
Diagnostic criteria must be clearly stated, easy

to use and easy to measure in a standard
manner under a wide variety of
circumstances by different people
Diagnostic criteria may change quite rapidly as

knowledge or techniques improve.
Definitions used in clinical practice are less

rigidly specified and clinical judgment is
more important in diagnosis
The development of criteria to

establish the presence of disease
requires definition of normality
and abnormality
Difficult to define what is normal
No clear distinction between

normal and abnormal
Approaches in establishing
“normality”
Clinical question: Is the patient sick or well ?
 Problem (misclassification)
Clinical measurements
nominal asymptomatic
ordinal cut-off point
interval or ratio
Clinical measurements have skewed

distributions
Percentile method ( same prevalence rates)

Level at which treatment does more good than harm - Cost
In specific age groups for men and women at which treatment make
economic as well as medical sense
Criteria change from time to time
Approaches in establishing
“normality”
Clinical question: Is the patient sick or well ?
Normal Abnormal
common or usual being unusual
well being sick
not being treatable being treatable

Measures of disease frequency
Clinical question: How often does a disease occur ?
 Prevalence of a disease is the number of

cases in a defined population at a specified
point in time
– Point prevalence
– Period prevalence
 Incidence is the number of new cases

arising in a given period in a specified
population
Measuring disease frequency
The prevalence rate (P) for a disease is calculated

as follows:
Number of people with the disease or condition

P = ----------------------------------------------------------------- (x
factor)
Number of people in the population at risk at the
specified time
Incidence rate (I)

Number of people who get a
disease in a specified period
I = ---------------------------------------------------- X
(factor)
Sum of the length of time during which
each person in the population is at risk
Incidence rate
 The numerator is the number of new
events that occur in a defined time
period
 The denominator is the population at
risk of experiencing the event during
this period
 The most accurate way of calculating
incidence rate is to calculate the
person-time incidence rate (Incidence
Cumulative incidence rate or risk (CI)
Number of people who get a

disease during a specified period
CI = ---------------------------------------------------- X
(factor)
Number of people free of the disease in
the population at risk at the beginning of
the period
Factors influencing observed prevalence rate
Increased by: Decreased by:

Longer duration of the disease Shorter duration of disease
Prolongation of life of patient High case-fatality rate from disease

without cure
Increase in new case Decrease in new cases

(increase in incidence) (decrease in incidence)
In-migration of cases In-migration of healthy people
Out-migration of healthy people Out-migration of cases
In-migration of susceptible people Improved cure rate of cases
Improved diagnostic facilities

(better reporting)
 Prevalence studies do not usually

provide strong evidence of causality
 It is helpful in assessing the need for

health care and the planning of health
services
 Prevalence rates are often used to

measure the occurrence of conditions
for which the onset of disease may be
gradual
Cumulative incidence rate
 Unlike incidence rate, it measures the denominator

only at the beginning of a study
 This rate has a simplicity that makes it suitable for the

communication of health information to decision
makers
 Easy to interpret and provide a useful summary

measure
 It is useful approximation of incidence rate when the

rate is low or when the study period is short
Example
Relationship between cigarette smoking and incidence rate

Stroke in a cohort of 118,539 women
Person-years Stroke incidence ra

Smoking No. of cases of observation (per 100,000
Category of stroke (over 8 years) person-years)
Never smoked 70 395,594 17.7

Ex-smoker 65 232,712 27.9
Smoker 139 280,141 49.6
Total 274 908,447 30.2
274
CI = ------------ x 1000 = 2.3 per 1000
118,539
Case-fatality rate
a measure of the severity of a disease
No. of deaths from a disease
in a specified period
Case fatality rate = ------------------------------------------ X
100
(CFR) No. of diagnosed cases of the
disease in the same period
USE OF AVAILABLE INFORMATION
(Mortality)
Number of deaths in a specified

period
Crude mortality rate =
--------------------------------------------------------- X F
(CMR) Average total population during that
period
This mortality can be made specific as to age, sex or

cause
Not appropriate to use for comparison because death

varies
according age, sex, race, socio-economic class and other
factors
Standardization of rates
(Adjustment of rates)
1. Direct adjustment of rates

This requires the selection of some population, called a standard
population, to which the age-specific rates for each population
can be applied.
2. Indirect adjustment of rates

Standardization is based on age-specific rates rather than age
composition
The population whose rates form the basis for comparison is

referred to as the “standard population”
The larger of the two populations is usually chosen as standard

because its rates tend to be more stable
If developed and an undeveloped country are

compared, the developed country would probably be
taken as the standard
A common way of carrying out indirect age-adjustment

is to relate the total expected deaths thus obtained to
observed deaths through a formula known as the
Standardized Mortality Ratio (SMR)
Total observed deaths in a population

SMR = -------------------------------------------------------
Total expected deaths in that population
Interpretation :
If this mortality ratio is greater than 1, it means that

more deaths are observed in the smaller or
comparison population than would be expected on the
basis of rates in the larger (standard) population
If the ratio is less than 1, fewer deaths are observed

than expected
Example: Direct method
Comparison of death rates in two populations by age
Annual Annual
Age-specific Number Crud
Age Population Death rate of Death r
(years) Number Proportion (per 1000) Deaths (per 10
(1) (2) (3) (4) (5) (6)

ation A < 15 1,500 0.30 2 3
15 – 44 2,000 0.40 6 12
≥ 45 1,500 0.30 20 30
45
All ages 5,000 1.00 45 ---------
5,00
ation B < 15 2,000 0.40 2 4
15 – 44 2,500 0.50 6 15
≥ 45 500 0.10 20 10
2
All ages 5,000 1.00 29 --------
5,00
Computation of Expected Number of Deaths by Direct Method
Example 1 : Identical Age-specific Rates
Population A Population B
Age-specific Age-specific
Age Standard Population Death Rate Expected Death Rate Expe
(years) (A and B Combined) per 1000 Deaths per 1000 Dea
(1) (2) (3)=(2)x(1) (4) (5)=
< 15 3,500 2 7 2 7
15 – 44 4,500 6 27 6
≥ 45 2,000 20 40 20
All ages 10,000 74
Conclusion : There is truly no difference between A and B in risk of de

Computation of Expected Number of Deaths by Direct
Method
Example 2 : Different Age-specific Rates
Population A Population
B
Age-specific Age-
specific
Age
< 15 Standard Population
3,500 Death Rate
2 Expected
7 Death2Rate
Expected 7
(years)
15 – 44 (A and4,500
B Combined) per 1000
6 Deaths
27 per 1000
10
Deaths 45
≥ 45 2,000 20 40 20
40
All ages 10,000 74

92
74
92Conclusion : There is difference between A and B in risk of death
Example of Indirect Method
Deaths by Age and Photofluorogram Reading (Whites) for

Three-and-a-Half Year Observation Period,
Muscogee County, Georgia, 1946
egative for Cardiovascular Disease Suspect for Cardiovascular
Age-specific Disease
e in 1946 Number of death rates Number o
ears) Population Deaths per 100 Population D
15 – 34 13,681 35 0.25 23 1
35 – 54 8,838 102 1.15 24 5
55 and over 2,253 149 6.61 65 14
---------- ------- ------- -----
All ages 24,772 286 112 20
Crude death rate per 100 1.15 17.9

Percentage Distribution by Age of Negatives and
Suspects, Muscogee County, Georgia
Negative for Suspect for

Cardiovascular Disease Cardiovascular Disease
Age Percentage Percent

(years) Number of Population Number of Popula
15 – 34 13,681 55.2 23 20.5

35 – 54 8,838 35.7 24 21.4
55 and over 2,253 9.1 65 58.0
All ages 24,772 100.0 112 99.9

Calculation of Standardized Mortality Ratio for
Suspects Compared with Negatives,
Muscogee County, Georgia
Death Rates per 100 Expected Deaths Observe
for Persons Negative among “Suspects” Deaths
ge Number of for Cardiovascular According to Rates among
ars) “Suspects” Disease for Negatives “Suspec
(1) (2) (3) = (1) x (2) (4)
– 34 23 0.25 .1 1
– 54 24 1.15 .3 5
and over 65 6.61 4.3 14
ages 4.7 20
Observed deaths 20
SMR = -------------------------- = --------- = 4.25
Expected deaths 4.7
Mortality
No. of deaths in a year of children

less
than 1 year of age
Infant mortality rate =
------------------------------------------------------ X F
No. of live births in the same
year
A measure of overall health status for a given population
It is based on the assumption that it is particularly

sensitive to
socio-economic changes and to health care intervention
Other measures of mortality in early childhood are :

1. Fetal death rate
Mortality
Child mortality rate

is based on deaths of children aged 1 – 4 years and is important
because accidental injuries, malnutrition and infectious diseases
are common in this age group
Maternal pregnancy-related
deaths in a year
Maternal mortality rate = -------------------------------------
Total births in the same year
Life expectancy
is the average number of years an individual of a
given age is expected to live if current mortality rates continue
Life Expectancy (years) at selected
ages for four countries
Age Mauritius Bulgaria USA Japan
Birth 65.0 68.3 71.6

75.8
45 years 25.3 27.3 30.4
32.9
65 years 11.7 12.6 15.0
16.2
DIAGNOSIS
Clinical question: How accurate are tests used to diagnose disease
Diagnostic test – the objective is to diagnose any treatab

disease present
Characteristics of a diagnostic test
Reliable – gives the same measurement when repeated more than o

Valid - measures what it intends to measure
Accurate – correctly determines those with disease and those withou
Easy to use – can be performed by other people without difficulty
Not expensive – affordable
Safe and acceptable
DIAGNOSIS
Clinical question: How accurate are tests used to diagnose
disease ?
Gold standard
– a sounder indication of truth or a standard of
accuracy
- a new diagnostic test is compared
- elusive (not available)
- expensive and risky – biopsy, surgical
exploration,
autopsy
- sometimes simple – throat swab culture
Normal Group Abnormal Group
Cut-off points
80 90 100 110 120 130 140 150 160 170
Bl ood L e v e l ( mg / 100 ml )
DIAGNOSIS
disease ?
Validity of a diagnostic test
a = no. of true positives, b = no. of false positives
c = no. of false negatives, d = no. of true negatives
Sensitivity = probability of a positive test
people with the disease
= a/(a + c)
Specificity = probability of a negative tes
people without the disease
Positive predictive value = probability of the person havi
the disease when the test
is positive
= a /(a + b)
Negative predictive value = probability of the person not
having the disease when the
test is negative
= d / (c + d)
DISEASE
Clinical question: How accurate are tests to diagnose
disease ?
Use of multiple diagnostic tests
use of imperfect diagnostic tests, with less

than
100% sensitivity and specificity, a single test
frequently results in a probability of disease
that is neither very high or very low.
DISEASE
disease ?
Parallel tests (all at once)

- used when rapid assessment is necessary as in
hospitalized or emergency patients, or for ambulatory
patients who cannot return easily for evaluation
because they have come from a long distance
- Parallel tests generally increase the sensitivity and,

therefore, the negative predictive value for a given
disease prevalence above those of each individual
test. On the otherhand, specificity and positive
predictive value are lowered
- Parallel testing is useful when the clinician is faced

with the need for a very sensitive test but has
available only two or more relatively insensitive ones.
DISEASE
disease ?
Serial testing (consecutively, based on previous

test result)
- used when rapid assessment is not required
- used when some of the tests are expensive
or risky
- maximizes specificity and positive predictive
value but lowers sensitivity and the negative
predictive value.
- the process is more efficient if the test with
the highest specificity is used first.
ffect of Sequence is Serial Testing: A Then B versus B Then A
Prevalence of Disease
Number of patients tested 1000
Number of patients with disease 200 (20% prevalence)
Sensitivity and Specificity of the Tests

Test Sensitivity Specificity
A 80 90
B 90 80
Sequence of Testing
Begin with Test A Begin with Test B
Disease Disease
+ - + -
A + 160 80 240 B + 180 160 340
- 40 720 760 - 20 640 660
200 800 1000 200 800 1000
240 Patients Retested with B 340 Patients Retested with A

Disease Disease
+ - + -
B + 144 16 160 A + 144 16 160
- 16 64 80 - 46 144 180
160 80 240 180 160 340
DISEASE
disease ?
Statements about validity test
 Sensitivity and specificity are inversely related.
 A sensitive test can pick up most cases of the

disease but it will erroneously label as positive many
persons who do not have the disease.
 A highly specific test will correctly label as negative

those who do not have the disease but it will miss
many cases.
ade-Off between Sensitivity and Specificity when Diagnosing Diabetes
Blood Sugar Level
2 hr after Eating Sensitivity Specificity
(mg/100 mL) (%) (%
70 98.6 8.8
80 97.1 25.5
90 94.3 47.6
100 88.6 69.8
110 85.7 84.1
120 71.4 92.5
130 64.3 96.9
140 57.1 99.4
150 50.0 99.6
160 47.1 99.8
170 42.9 100.0
180 38.6 100.0
190 34.3 100.0
200 27.1 100.0
DISEASE
disease ?
 A very sensitive test gives a low positive predictive

value since it produces many false positive.
Conversely, a very specific test gives a high positive
predictive value.
 Sensitivity and specificity are unaffected by the

prevalence of the disease or condition. Since
sensitivity depends only on those with the disease or
condition and specificity only on those without the
disease or condition.
DISEASE
disease ?
 Uses of sensitive tests

A sensitive test should be chosen when there is an
important penalty for missing a disease (dangerous
but treatable condition)
A sensitive test is most helpful to the clinician when

the test result is negative (to rule out disease)
 Uses of specific tests
Highly specific tests are needed when false-positive
results can harm the patient physically, emotionally,
or financially.
A specific test is most helpful when the test result is

positive
DISEASE
disease ?
Problems:
 Lack of information on negative tests
 Lack of information on test results in the
nondiseased
 Lack of objective standards for disease
 Consequences of imperfect standards
If a new test is compared with an old (but inaccurate)
standard test, the new test may seem worse even
when it is actually better
DISEASE
disease?
Reliability and validity

Measurement error
Instrument The means of making the
measurement
Observer The person making the measurement
Biologic variation
Within individuals Changes in people with time and

situation
Among individuals Biologic differences from person to

DISEASE
disease?
Types of epidemiological study
Type of study Alternative name Unit of study
Observational studies
Descriptive studies
Analytical studies
Ecological Correlational Population
Cross-sectional Prevalence Individuals
Case-control Case-reference Individuals
Cohort Follow-up Individuals
Experimental studies Interventional studies

Randomized controlled trials Clinical trials Patients
Field trials Healthy
people
Community trials Community intervention
(Descriptive studies)
Case reports
- detailed presentations of a single case or a handful
of cases
- means of describing rare clinical events
- describe unusual manifestations of disease
- elucidate the mechanisms of disease and treatment
- place issues before medical community and often
trigger
more decisive studies
- susceptible to bias
(Descriptive studies)
Case-series
- a simple descriptive account of interesting
characteristics observed in a group of patients
- study larger group of patients (e.g. 10 or more) with
particular disease
- describe the clinical manifestations of disease and
treatments in a group of patients assembled at one
point in time
- absence of a comparison group, not conclusive
- hypothesis-generating
- selection bias
(Observational studies)
Ecological studies
- aggregate risk studies
- units of analysis are populations or groups of people

rather
than individuals
- rely on data collected for other purposes; data on

different exposures and on socioeconomic factors may
not be available
- ecological fallacy (bias)

Cross-sectional Study (Prevalence Study)

Observational studies
Cross-sectional (Prevalence study)
(Observational Studies)
Cross-sectional studies (Prevalence
studies)
- measure the prevalence of disease
- measurements of exposure and effect are

made at
the same time
- useful for investigating exposures that are

fixed
characteristics of individuals, such as
ethnicity,
socio-economic status and blood group, or
chronic

studies)
- In sudden outbreaks of disease it is the

most convenient first step in an investigation
into the cause
- Rare disease, conditions of short duration or

diseases with high case fatality are often not
detected

studies)
- short-term and therefore less costly
- provide no direct estimate of risk
- prone to bias from selective survival
- estimates of prevalence may be biased by

the exclusion of cases in which death or
recovery are rapid
Case-control studies
- longitudinal studies (looking backward from
the disease to a possible cause)
- use new (incident) cases
- used to investigate cause (etiology) of

disease, esp. rare diseases
- used odds ratio

Case-control studies
- relatively efficient, requiring smaller
sample than cohort study
- completed faster and more economical
- earliest practical observational
strategy for determining an
association
- antecedent-consequence uncertainty
Table arrangement and formula for Odds
ratio (OR)
Disease No disease
Total
Risk factor present A B

A+B
Risk factor absent C D

C+D
Total A+C B+D
[A / (A+C)] / [C / (A+C)] A/C

Odds ratio – measure of the strength

association
Interpretation of Odds ratio
 The odds of having the disease in question are
OR times greater among those exposed than
those with no exposure
 The larger the value of OR, the stronger the
association between the disease in question and
exposure to the risk factor
 When the value of OR is close to 1, the disease
and the exposure to the risk factor are unrelated
(Observational study)
Interpretation of Odds ratio

 Value of OR less than 1 indicates a negative
association (i.e., protective effect) between
the risk factor and the disease
 For rare disease (e.g., most chronic diseases
with disease prevalence of less than 10%),
OR approximates RR
Example of case-control study
Association between recent meat consumption and

enteritis necroticans in Papua New Guinea
Exposure
(recent meat ingestion)
Yes No
Total
Disease Yes 50 11
61
(enteritis necroticans) No 16 41
57
Total 66 52
Example of case-control study
[A / (A+C)] / [C / (A+C)] A/C

AD
OR = -------------------------------- = -------- =
-----
[B / (B+D)] / [D / (B+D)] B/D
BD
50 X 41
OR = ------------- = 11.6
11 X 16
The cases were 11.6 times more likely than

Cohort studies
Past Present Future
Historical
cohort
Cohort Follow-up
assembled
Concurrent
cohort
Cohort Follow-up
assembled
Cohort studies
- longitudinal studies (forward)
- provide the best information about the
causation of disease
- most direct measurement of the risk of
developing disease
- provide the possibility of estimating
the attributable risks
- use relative risk
Cohort studies
- most closely resemble experimental
studies
- Long-term, not always feasible
- Sample size required for the study
extremely large
- Attrition is most serious problem
Table arrangement and formula for relative
risk (RR)
Disease No Disease Total
Risk factor present A B A+B
Risk factor absent C D C+D
Total A+C B+D
A / (A + B)
RR = -----------------
C / (C + D)
Interpretation of relative risk (RR)

 The disease (or other health related outcome) is
RR times more likely to occur among those
exposed than among those with no exposure
 The larger the value of RR, the stronger the
association between the disease in question and
exposure to the risk factor
Interpretation of relative risk (RR)

 Value of RR close to 1 indicates that
the disease and exposure to the risk
factor are unrelated
 Value of RR less than 1 indicates a
negative association between the risk
factor and the disease (i.e., protective
rather than detrimental)
Example of cohort study
Problem:
A county school system provides lunch to
10,000
school children. During the first week of school,
2,500
of these children ate chicken salad later shown
to be
contaminated with salmonella. The entire
population
Example of cohort study
Diarrhea No Diarrhea
Exposure (D+) (D-)
Totals
E+ 30 2,470
2,500
E- 60 7,440
7,500
A / (A+B)
Totals 30 / 2,500 90 9,910
RR = ---------------
10,000 = ----------------- = 1.5
C / (C+D) 60 / 7,500
1.5 times greater than in children with no such exposure

Advantages and disadvantages of different observational
study designs
Ecological Cross- Case- Cohort
sectional control
bability of:
selection bias NA medium high low
recall bias NA high high low
loss to follow-up NA NA low high
confounding high medium medium low
me required low medium medium high
t low medium medium high
Applications of different observational study designs
Ecological Cross- Case- Cohort

sectional control
stigation of rare disease ++++ - +++++

stigation of rare cause ++ - - +++
ng multiple effect of + ++ - +++
use
y of multiple exposure ++ ++ ++++ +
d determinants
surements of time ++ - + +++
ationship
ct measurement of - - + +++
idence
stigation of long - - +++
ent periods
(Experimental studies)
Randomized controlled trials (RCTs)

- Gold standard or reference in medicine
- Provide the greatest justification for

concluding causality
- Subject to the least number of
problems or biases
- Best study design to establish the
efficacy of a treatment or a procedure
Randomized controlled trials (RCTs)

- Expensive and time-consuming
- Difficult to obtain approval to perform
properly designed clinical trials
Relative ability of different types of study to “prov
causation
Type of study Ability to “prove” causation
Randomized controlled trials Strong

Cohort studies Moderate
Case-control studies Moderate
Cross-sectional studies Weak
Ecological studies Weak
Bias in Clinical Observation
 Selection bias occurs when comparisons are
made between groups of patients that differ in
determinants of outcome other than the one under
study
 Measurement bias occurs when the methods of

measurement are dissimilar among groups of
patients
 Confounding bias occurs when two factors are

associated (“travel together”) and the effect of one
is confused with or distorted by the effect of the
other
Methods of Controlling Selection
Bias
Phase of Phase of
Study
Method Description Design
Analysis
Randomization Assign patients to groups in a way that +

gives each patient equal chance of
falling into one or the other group
Restriction Limit the range of characteristics of +

of patients in the study
Matching For each patient in one group select one +

or more patients with the same
characteristics (except for the one
under study) for a comparison group
Stratification Compare rates within subgroups (strata)

+
with otherwise similar probability of the
Methods for Controlling Selection
Bias
Phase
of Study
Method Description Design
Analysis
Adjustment
Simple Mathematically adjust crude rates for one

+
or few characteristics so that equal weight
is given to strata of similar risk
Multiple Adjust for difference in large number of factors

+
related to outcome, using mathematical
modelling techniques
Best case/ Describe how different the results could be

Cause
Clinical question: What conditions lead to
disease ? What are the pathogenetic
mechanisms of disease ?
Webster’s definition
“something that brings about an effect
or a result”
Medicine : “etiology”
“pathogenesis” “mechanisms” or “risk
factors”
Importance: prevention, diagnosis and

treatment of disease
Cause
Concepts of Cause
Single causation (Koch’s postulates)

a particular disease has one cause and a
particular cause results in one disease
5. The organism must be present in every case of the
disease
6. The organism must be isolated and grown in pure
culture
7. The organism must cause a specific disease when
inoculated into an animals and
8. The organism must then be recovered from the
Cause
disease ?
What are the pathogenetic mechanisms of
disease ?
Multiple causation (Web of causation)
Effects never depend on single isolated

causes, but rather develop as the result of
chains of causation in which each link itself is
the result of “a complex genealogy of
antecedents.”
Many factors act together to cause disease
Cause
Concept of Cause
A cause must precede a disease
A cause is termed sufficient when it

inevitably produces or initiates a
disease
A cause is termed necessary if a disease

cannot develop in its absence
Cause
A sufficient cause is not usually a single factor,
but often comprises several components
It is not necessary to identify all the

components of a sufficient cause before
effective prevention can take place
Each sufficient cause has a necessary cause as

a component
A causal factor on its own is often neither

necessary nor sufficient
Cause
Cause
Concept of cause
Proximity of cause to effect
Disease is also determined by less specific, more
remote causes or risk factors, such as people’s
behavior or characteristics of their environment.
These factors may be even more important

causes of disease than are pathogenetic
mechanisms
If the pathogenetic mechanism is not clear,

knowledge of
risk factors may still lead to very effective
Causes of tuberculosis
Exposure to
Crowding Mycobacterium
Malnutrition
Vaccination
Genetic Tissue Invasion and Reaction
SUSCEPTIBLE HOST INFECTION TUBERCULOSIS
Risk Factors for Mechanisms of

Tuberculosis Pathogenesis Tuberculosis
Distant from Outcome Proximal to Outcome

Cause
Concept of cause
Interplay of multiple causes
Synergism – the joint effect is greater than
the sum of the effects of the individual
causes
Antagonism – the joint effect is lesser
Effect Modification – a special type of

interaction
A substantial impact on a patient’s health by

changing
Cause as a risk factor
Risk refers to the probability of some untoward
event
Risk indicates the likelihood that people who

are exposed to certain factors (risk factors)
will subsequently develop a particular
disease
Risk factor refers to condition, physical

characteristic, or behavior that increases the
probability (i.e., risk) that a currently healthy
individual will develop a particular disease.
mechanism of disease ?
Exposure to risk factor can occur at a single
point in time or over a period of time
ever exposed
current dose
largest dose taken
total cumulative dose
years of exposure
years since first contact
Recognizing risk
Large risks associated with effects that occur

rapidly after exposure are easy for anyone to
recognize
Most morbidity and mortality are caused by

chronic diseases. The relationship between
exposure and disease are far less obvious –
latency period
Comparing disease occurrence
among exposed and unexposed
Absolute comparison
 Risk difference, also called attributable risk (exposed),
excess risk or absolute risk
 Attibutable fraction (exposed) or etiological fraction
(exposed)
 Population attributable risk or attributable fraction
(population)
Relative comparison
 Risk ratio
 Standardized mortality ratio
Relationship between cigarette smoking and incidence
rate of stroke in a cohort of 118,539 women
Smoking Person-y ears Stroke incidence rate

category No. of cases of observation (per 100,000
of stroke (over 8 years) person-years)
Never smoked 70 395,594 17.7

Ex-smoker 65 232,712 27.9
Smoker 139 280,141 49.6
Total 274 908,447 30.2
Risk difference
is the difference in rates of occurrence
between exposed and unexposed groups
useful measure of the extent of the public

health problem caused by the exposure
Example:
49.6 – 17.7 = 31.9 per 100,000 person-
years
Attributable fraction (exposed)
is the proportion of the disease in the specific
population that would be eliminated in the absence of
exposure
determined by dividing the risk difference by the rate

of occurrence among the exposed population
Example:
[(49.6 – 17.7) / 49.6] x 100 = 64%
Interpretation: One would expect to achieve a 64%

reduction in the risk of stroke among the women
smokers if smoking were stopped, on the assumption
that smoking is both causal and preventable
Population attributable risk [attributable fraction
(population)]
is a measure of the excess rate of disease in a total study

population which is attributable to an exposure
useful for determining the relative importance of exposures for

the entire population and is the proportion by which the
incidence rate of the outcome in the entire population would be
reduced if exposure were eliminated.
I p − I u 30.2 – 17.7
AFp = = ------------------ = 0.414 o r 41.4%
Ip 30.2
Risk ratio or relative risk
the ratio of the risk of occurrence of a disease among
exposed people to that among the unexposed
better indicator of the strength of an association than

the risk difference
used in assessing the likelihood that an association

represents a causal relationship
Example:
RR = 49.6 / 17.7 = 2.8
Uses of risk factor
3. predict the occurrence of disease

4. marker of disease outcome
5. improve the positive predictive value of a
diagnostic test
6. prevent disease
Cause
Establishing cause
In clinical medicine, it is not possible to
prove causal relationship beyond any
doubt. It is only possible to increase
one’s conviction of a cause and effect
relationship, by means of empiric
evidence, cause is established.
Cause
Establishing cause
Factors that are considered causes at

one time are sometimes found to be
indirectly related to disease later,
when more evidences are available
Cause
Establishing cause
Two factors – the suspected cause and the
effect – obviously must appear to be
associated if they are to be considered as
cause and effect
However, not all associations are causal
Two factors may be associated but not

causal
due to the presence of selection and
Guidelines for
Causation
Temporal Does the cause precede the effect ? (essential)
Plausibility Is the association consistent with other knowledge ?
(mechanism of action; evidence from experimental
animals)
Consistency Have similar results been shown in other studies ?
Strength What is the strength of the association
between the cause and the effect ? (relative risk)
Dose-response Is increased exposure to the possible cause associated
relationship with increased effect ?
Reversibility Does the removal of a possible cause lead to reduction

of disease risk ?
Study design Is the evidence based on a strong study design ?
Judging the evidence How many lines of evidence lead to the conclusion ?
Natural history of a disease and
prognosis
Clinical question: What are the consequences of having a
disease ?
Prognosis
is a prediction of the future course of disease
following its onset
Natural history of disease

refers to the stages of a disease
a. Natural
b. Clinical course
Natural history of disease and
prognosis
disease ?
Prognostic factors
are conditions that are associated with a
given outcome of the disease
Risk factors Prognostic

factors
events being counted is a variety of

consequences
the onset of disease of disease are
counted
predict low probability describe

relatively frequent
prognosis
Clinical question: What are the consequence of having a
disease ?
Multiple prognostic factors and

prediction rules
A combination of factors may give a more

precise prognosis than each of the same
factors taken one at a time
Clinical prediction rules estimate the

probability of outcomes according to a set of
patient characteristics
Outcomes of Disease (the Five Ds)
Death A bad outcome if untimely

Disease A set of symptoms, physical signs, and laboratory
abnormalities
Discomfort Symptoms such as pain, nausea, dyspnea, itching,
and tinnitis
Disability Impaired ability to go about usual activities at hoe,
work, or recreation
Dissatisfaction Emotional reaction to disease and its care, such a
sadness or anger
prognosis
disease ?
 Descriptions of prognosis should include the
full range of manifestations that would be
considered important to patients
 Cohorts in prognostic studies are observed

starting from a point in time,, called zero
time.
 This point should be specified clearly and be

the same well-defined location along the
course of disease (e.g. onset of symptoms,
time of diagnosis or beginning of treatment)
for each patient
prognosis
Clinical question: What are the consequence of having a
diseaseCommonly
Rates ? Used to Describe Prognosis
Rate Definition
5-year survival Percent of patients surviving
5 years from
some point in the course of
their disease
Case fatality Percent of patients with a disease
who die
of it
Disease-specific mortality Number of people per 10,000
population
dying of a specific disease
Response Percent of patients showing some
evidence of improvement
following an
intervention
prognosis
disease ?
 Survival analysis (Kaplan-Meir analysis)

– a way of estimating the survival of a cohort over
time
 Life table analysis

Treatment
Clinical question: How does treatment change
the course of disease?
Usually the effects of treatment are much

less obvious and most interventions require
research to establish their value
Specific interventions must do more good

than harm among patients who use them
(efficacious and effective)
The most desirable method for measuring

efficacy and effectiveness is that of the
randomized controlled trial
Treatment
Intervention studies
 Clinical trials
 Controlled trials
 Uncontrolled trials
 Concurrent control
Treatment
Types of clinical trial (according to purpose)

 Prophylactic trials, e.g. immunization,
contraception
 Therapeutic trials (drug treatment, surgical
procedures
 Safety trials (side-effects of drug)
 Effectiveness trials (theoretical, use, and
extended use effectiveness of contraceptive
methods)
 Risk factor trials (proving etiology of disease)
Treatment
Phases of Clinical Trials

 Phase I Clinical Trials
experimental animals used to establish that the
new
agent is effective and suitable for human use
1st phase in humans – pharmacologic and
toxicologic
studies
 Phase 2 Clinical Trials
assess the effectiveness of the drug or device
determine the appropriate dose
investigate its safety
Treatment
 Phase 3 Clinical Trials (Classical phase)

performed on patients with consent
carried out mostly on hospital in-patients
assess the effectiveness, safety and
continued use of the drug/device
 Phase 4 Clinical Trials
a trial in normal field or program setting
reassess effectiveness, safety, acceptability
and continued use of the drugs
Prevention
Clinical question: Does an intervention on well people
keep disease from arising? Does early detection and
treatment improve the course of disease ?
Prevention (Webster’s definition) –” the

act of keeping from happening”
In clinical medicine, the definition is

restricted; depending on when in the
course of disease interventions are
made
Prevention
treatment improve the course of disease?
Levels of prevention
Clinical
Onset Diagnosis
ASYMPTOMATIC
NO DISEASE DISEASE CLINICAL COURSE
Primary Secondary Tertiary
move risk Early detection Reduce

ors and treatment complications
Prevention
keep the disease from arising? Does early detection and
Level of prevention Phase of disease

Target
Primary Specific causal factor

Total population,
selected groups
and
healthy
individuals
Secondary Early stage of disease Patients
Prevention
Primary prevention
Immunization (communicable diseases)
Folic acid administration to prevent neural tube
defects
Counseling patients to adopt healthy lifestyles
Chlorination and fluoridation of the water supply

Laws mandating seatbelt use in automobile and
helmets for motorcycle use
Use of earplugs or dust masks in certain
occupational setting
Prevention
Secondary prevention
Pap smear
Screening test –
identification of an unrecognized
disease or
risk factor by history taking, physical
examination, laboratory test or other
procedure
that can be applied rapidly
Criteria for instituting a screening
program
Disease Serious
High prevalence of preclinical stage
Natural history understood
Long period between first signs and overt
disease
Diagnostic test Sensitive and specific

Simple and cheap
Safe and acceptable
Reliable
Diagnosis and Facilities are adequate

Treatment Effective, acceptable, and safe treatment
available
Prevention
Tertiary prevention
Limitation of disability
Rehabilitation
The goal here is not to prevent death but to

maximize the amount of high-quality time a
patient has left.
Prevention
Health maintenance or Periodic health

examination
Procedures are performed on patients without
specific complaints, to identify and modify

risk
factors to avoid the onset or to find disease
early
in its course so that by intervening patients
remain
well
Criteria for Deciding Whether a Medical
Condition Should Be Included in Periodic Health
Examination
1. How great is the burden of suffering caused by the
condition in terms of:
Death Discomfort
Disease Dissatisfaction
Disability Destitution
5. How good is the screening test, if one is to be
performed, in terms of:
Sensitivity Cost
Specificity Safety
Simplicity Acceptability
3. a. For primary prevention, how effective is the
intervention?
or
b. For secondary prevention, if the condition is
found, how
effective is the ensuing treatment in terms of:
Efficacy
Patient compliance
Early treatment being more effective than later
Prevention
keep the disease from arising? Does early detection and
Health maintenance or Periodic health

examination
How much harm for how much good?

Before undertaking a health promotion
procedure on a patient, especially if the
procedure is controversial among expert
groups, the clinician should discuss both the
pros (probability of and hoped for health
benefits) and cons (probability of unintended
effects) of the procedure with the patient.
Thank You
The spectrum of illness from communicable
disease
INAPPARENT MILD SEVERE

DEATH
INFECTION DISEASE DISEASE
No signs or Clinical illness with signs and symptoms

symptoms
Origin
 Over 2,000 years ago,

Hippocrates “environmental
factors can influence the
occurrence of disease”
 In the early 19th century, the

distribution of disease in specific
human population groups was
measured
John Snow’s epidemiological
studies on the risk factor of Cholera
in London
Deaths from Cholera in districts of London
Supplied by two water companies,
8 July to 26 August 1854
Water Supply Population No. of deaths Cholera death

Company 1851 from cholera rate per 1000
population
________________________________________________________
Southwark 167,654 844 5.0
Lambeth 19,133 18 0.9

ACHIEVEMENTS IN EPIDEMIOLOGY
 Eradication of Smallpox
 Identification of methylmercury – “Minamata
Disease”
 Identification of factors causing Rheumatic
fever and Rheumatic heart disease
 Iodine deficiency disease
 AIDS, SARS
PROGNOSIS
 Survival curve
1. Actuarial or life table analysis
(Cutler-Ederer method)
3. Kaplan-Meier curve
Patient Date of Transplant Date lost to Follow-up Date of Kidney Failure Months in Stud
1 1 – 11 - 1979 4 – 8 - 1978 2
2 1 – 18 - 1978 23
3 1 – 29 – 1978 23
4 4 – 4 – 1978 4 – 24 – 1978 <1
5 4 – 19 – 1978 20
6 5 – 10 – 1978 19
7 5 – 14 – 1978 8 – 28 – 1978 3
8 5 – 21 – 1978 11 – 2 – 1978 5
9 6 – 6 – 1978 11 – 15 – 1978 17
10 6 – 17 – 1978 18
11 6 – 21 – 1978 18
12 7 – 22 – 1978 11 – 7 – 1978 3
13 9 – 27 – 1978 15
14 10 – 5 – 1978 1 – 20 – 1979 3
15 10 – 22 – 1978 14
16 11 – 15 – 1978 13
17 12 – 6 – 1978 12
18 12 – 12 – 1978 12
19 2 – 1 – 1979 10
20 2 – 16 – 1979 10
21 4 – 8 – 1979 8
22 4 – 11 – 1979 8
23 4 – 18 – 1979 8
24 6 – 26 – 1979 8 – 4 – 1979 1
25 7 – 3 – 1979 5
26 7 – 12 – 1979 5
27 7 – 18 – 1979 8 – 1 – 1979 4
28 8 – 23 – 1979 4
29 10 – 16 – 1979 2
30 12 – 12 – 1979 <1
31 12 – 24 – 1979 <1
Data for Actuarial (Life Table) Analysis of Rejection (Deaths) of Kidneys
C. Arrangement of survival data

onths since Alive at beginning Rejection during Withdrawn alive
ry into study of interval interval lost to follow-
ni di Wi
up to 2 31 3 2
up to 4 26 3 2
up to 6 21 1 3
up to 9 17 0 3
up to 12 14 0 2
up to 15 12 0 4
up to 18 8 1 1
up to 21 6 0 4
up to 24 2 0 2
B. Actuarial Calculation
nths since Probability of Probability of Cumulative Probabil

y into study rejection or death kidney retention of kidney retent
qi= di / [ni – (w/2)] pi = 1 – qi si = pipi-1pi-2….p
p to 2 3/[31 – (2/2)] =.10 .90 .90

p to 4 3/[26 – (2/2)] =.12 .88 .79
p to 6 1/[21 – (3/2)] =.05 .95 .75
p to 9 0/[17 – (3/2)] = 0 1.00 .75
p to 12 0/[14 – (2/2)] = 0 1.00 .75
p to 15 0/[12 – (4/2)] = 0 1.00 .75
p to 18 1/[8 – (1/2)] = .13 .87 .65
p to 21 0/[6 – (4/2)] = 0 1.00 .65
p to 24 0/[2 – (2/2)] = 0 1.00 .65
Calculation for confidence band for actuarial curve
 qi 
si ∑  

( )
 ni − d i − 1 w
2 i
nterval qi ni di wi si
0 – 2 0.10 31 3 2 0.0037
2 – 4 0.12 26 3 2 0.0055
4 – 6 0.05 21 1 3 0.0027
6 – 9 0 17 0 3 0
9 – 12 0 14 0 2 0
2 – 15 0 12 0 4 0
5 – 18 0.13 8 1 1 0.0200
8 – 21 0 6 0 4 0
1 – 24 0 2 0 2 0

Applied Epidem

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Applied Epidem

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APPLIED EPIDEMIOLOGY

Antonio E. Chan, M.D.

1. Define epidemiology and outline its

1. Understand diagnostic test in relation

 Appreciate the differing approaches

The study of the distribution and

 To understand the course of the

• Causation Good health Ill health

2. Natural history Good health Subclinical Clinical

3. Description of health status

change with age, etc

is the science of making predictions about

EPIDEMIOLOGY + CLINICAL MEDICINE

Abnormality Is the patient sick or well ?

 Data on vital events – birth and death

Health is defined as “a state of

Epidemiologist’s definition of health

Diagnostic criteria are usually based on

1. Hepatitis presence of antibodies in the blood

Major Manifestations Minor Manifestations

The presence of disseminated Kaposis sarcoma or

MAJOR SIGNS MINOR SIGNS

Weight loss > 10% Persistent cough > 1

Diagnostic criteria must be clearly stated, easy

Diagnostic criteria may change quite rapidly as

Definitions used in clinical practice are less

The development of criteria to

Difficult to define what is normal

No clear distinction between

Clinical measurements have skewed

Percentile method ( same prevalence rates)

common or usual being unusual

well being sick

not being treatable being treatable

 Prevalence of a disease is the number of

 Incidence is the number of new cases

The prevalence rate (P) for a disease is calculated

Number of people with the disease or condition

Incidence rate (I)

Cumulative incidence rate or risk (CI)

Number of people who get a

Increased by: Decreased by:

Prolongation of life of patient High case-fatality rate from disease

Increase in new case Decrease in new cases

In-migration of cases In-migration of healthy people

Out-migration of healthy people Out-migration of cases

In-migration of susceptible people Improved cure rate of cases

Improved diagnostic facilities

 Prevalence studies do not usually

 It is helpful in assessing the need for

 Prevalence rates are often used to

Cumulative incidence rate

 Unlike incidence rate, it measures the denominator

 This rate has a simplicity that makes it suitable for the

 Easy to interpret and provide a useful summary

 It is useful approximation of incidence rate when the

Relationship between cigarette smoking and incidence rate

Person-years Stroke incidence ra

Never smoked 70 395,594 17.7

Number of deaths in a specified

This mortality can be made specific as to age, sex or

Not appropriate to use for comparison because death

1. Direct adjustment of rates