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Prepared by
Environmental factors
(including lifestyle) Death
Good health
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
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
Populations Individuals
• Studies/Assessments • Diagnosis
• Prevention • Treatment
• Evaluation • Curing
• Planning • Caring
Clinical Question
Issue Question
Diagnostic tests
qualitative diagnostic test
quantitative diagnostic test
Normal (Gaussian) distribution
method
Percentile method
Therapeutic method
Predictive value method
Measuring Health and Disease
Laboratory:
Acute phase
reactants:
Abnormal ESR,
CRP,
leukocytosis
WHO CASE-DEFINITION FOR AIDS
Problem (misclassification)
Clinical measurements
nominal asymptomatic
ordinal cut-off point
interval or ratio
Normal Abnormal
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
Measuring disease frequency
Clinical question: How often does a disease occur ?
274
CI = ------------ x 1000 = 2.3 per 1000
118,539
Measuring disease frequency
Clinical question: How often does a disease occur ?
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)
Interpretation :
Annual Annual
Age-specific Number Crud
Age Population Death rate of Death r
(years) Number Proportion (per 1000) Deaths (per 10
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
< 15 3,500 2 7 2 7
15 – 44 4,500 6 27 6
≥ 45 2,000 20 40 20
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
74
92Conclusion : There is difference between A and B in risk of death
Example of Indirect Method
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
– 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
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
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
Bl ood L e v e l ( mg / 100 ml )
DIAGNOSIS
Clinical question: How accurate are tests used to diagnose
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 ?
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
Clinical question: How accurate are tests to diagnose
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
Clinical question: How accurate are tests to diagnose
disease?
Biologic variation
Observational studies
Descriptive studies
Analytical studies
Ecological Correlational Population
Cross-sectional Prevalence Individuals
Case-control Case-reference Individuals
Cohort Follow-up Individuals
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
Types of epidemiological study
(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
Types of epidemiological study
(Observational studies)
Ecological studies
Case-control studies
- longitudinal studies (looking backward from
the disease to a possible cause)
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
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
50 X 41
OR = ------------- = 11.6
11 X 16
Cohort studies
Past Present Future
Historical
cohort
Cohort Follow-up
assembled
Concurrent
cohort
Cohort Follow-up
assembled
Types of epidemiological study
(Observational studies)
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
Types of epidemiological study
(Observational studies)
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)
A / (A + B)
RR = -----------------
C / (C + D)
Types of epidemiological study
(Observational studies)
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
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
Adjustment
Webster’s definition
“something that brings about an effect
or a result”
Medicine : “etiology”
“pathogenesis” “mechanisms” or “risk
factors”
Concept of Cause
Exposure to
Crowding Mycobacterium
Malnutrition
Vaccination
Genetic Tissue Invasion and Reaction
SUSCEPTIBLE HOST INFECTION TUBERCULOSIS
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
Risk difference
is the difference in rates of occurrence
between exposed and unexposed groups
Example:
49.6 – 17.7 = 31.9 per 100,000 person-
years
Comparing disease occurrence
among exposed and unexposed
Attributable fraction (exposed)
is the proportion of the disease in the specific
population that would be eliminated in the absence of
exposure
Example:
[(49.6 – 17.7) / 49.6] x 100 = 64%
Example:
RR = 49.6 / 17.7 = 2.8
Cause as a risk factor
Clinical question: What conditions lead to
disease ? What are the pathogenetic
mechanisms of disease ?
Uses of risk factor
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
Clinical question: What conditions lead to
disease ? What are the pathogenetic
mechanisms of disease ?
Establishing 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
Prognosis
is a prediction of the future course of disease
following its onset
Prognostic factors
are conditions that are associated with a
given outcome of the disease
Intervention studies
Clinical trials
Controlled trials
Uncontrolled trials
Concurrent control
Treatment
Clinical question: How does treatment change
the course of disease?
Levels of prevention
Clinical
Onset Diagnosis
ASYMPTOMATIC
NO DISEASE DISEASE CLINICAL COURSE
selected groups
and
healthy
individuals
Secondary Early stage of disease Patients
Prevention
Clinical question: Does an intervention on well people
keep disease from arising? Does early detection and
treatment improve the course of disease?
Primary prevention
Immunization (communicable diseases)
Folic acid administration to prevent neural tube
defects
Counseling patients to adopt healthy lifestyles
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
Tertiary prevention
Limitation of disability
Rehabilitation
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
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
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