Department of Epidemiology, Medical University of Silesia
Jan E. Zejda

TOPICS
Roots of modern epidemiology
Epidemiology among health sciences
Definition of epidemiology
Epidemiological paradigms
Application of epidemiology in medical research
Clinical epidemiology

TOPICS
Roots of modern epidemiology
Epidemiology among health sciences
Definition of epidemiology
Epidemiological paradigms
Application of epidemiology in medical research
Clinical epidemiology

CHOLERA IN EUROPE
1829 in Orenburg (Russia)
1830 in Moscow (Russia)
1831
↓
Poland, Hungary, Austria, Prussia
1832
↓
England, France, Scandinavia,
Spain …

CHOLERA IN EUROPE
Second Wave of Epidemia
1848 in England: 53000
†††

Dr WILLIAM FARR
1807 – 1883
Physician
Founder of Medical Statistics
(measurement of health events: birth, mortality, etc.)

CHOLERA CARRIED BY AIR POLLUTED BY MIASMA
(miasma = rotting organic matter)
Farr’s hypothesis („miasma theory”)
Deaths due to cholera versus elevation of the residence place in London
Deaths
140
120
100
80
60
40
20
0
<20 20-40 40-60 60-80 80-100
Stopy nad poziomem morza
Feet above sea level
100-120 340-360
Źródło: Gordis L.: Epidemiology. W.B. Sounders Company, Philadelphia 1996)

MIASMA THEORY
(miasma in Greek = pollution)
Thickness of miasma layer
340-360 100-120 80-100 60-80 40-60
Stopy nad poziomem morza
Feet above sea level
20-40 <20

DR JOHN SNOW
1813 – 1858
One of the first physicians to test the use of ether and chloroform as anaesthetics.
Designer of devices to safely administer ether and chloroform.
C
2
H
5
OC
2
H
5
CHCl
3
↓
Kidney
Liver
Heart

JOHN SNOW (1813-1858) on causes of cholera epidemics in London

JOHN SNOW (1813-1858) on causes of cholera epidemics in London
Snow’s statistical argument regarding water-borne disease
Mortality distribution according to the place of residence / source of drinking water
Water Supply Company
Southwark&Vauxhall
Lambeth
Number of houses
40 046
26 107
Number of deaths
1263
98
Deaths rate
(n/10000 houses)
315
37
Source: Fox J.P. et al.: Epidemiology. Man and Disease. The Macmillan Company, London 1970)

JOHN SNOW (1813-1858) on causes of cholera epidemics in London

SNOW’S DISTINCT METHODS
• Symptoms of acute intestinal infection (medical background)
•
Location (plotting the cases)
•
Measurement of mortality rates (comparisons) observation → hypothesis → measurement knowledge → action

IMPORTANT MESSAGE
Cholera put under control long before the causative agent was discovered response
•
1848 - Establishment of General Health Department
(London)
•
1851 - International Health Conference (Paris)
•
1875 - Public Health Act (Great Britain): water supply, sewage transportation, etc.
•
1907 - Establishment of International Health Organization
(Paris)

ROBERT KOCH (1843 – 1910)
[Vibrio cholerae – 1884]

Koch – 1884 !

FILIPPO PACINI (1812 – 1883)
[Vibrio Cholerae – 1854]

EPIDEMIOLOGY TODAY
(from infectious to non-infectious diseases)
Non-infectious diseases
Ch. Niezakaźne
Ch. Zakaźne
Infectious diseases
↑ YESTERDAY TODAY
↑
√ ADVANCES IN MEDICINE
√ DEMOGRAPHY
√ QUALITY OF LIFE …

TOPICS
Roots of modern epidemiology
Epidemiology among health sciences
Definition of epidemiology
Epidemiological paradigms
Application of epidemiology in medical research
Clinical epidemiology

HEALTH SCIENCES
RESEARCH FIELD PRIMARY FOCUS
Health
Services
Epidemiology
Clinical Sciences
Biologic Sciences
Health care systems
Populations
Individual patients
Animal models, cells & transmitters, molecules, genes, drugs development
Source: Fletcher R.W., Fletcher S.W.: Clinical Epidemiology. The essentials .Lippincott Williams & Wilkins 2005

HEALTH SCIENCES
RESEARCH FIELD PRIMARY FOCUS
Health
Services
Epidemiology
Clinical Sciences
Biologic Sciences
Health care systems
Populations
Individual patients
Human & animal models, cells & transmitters, molecules, genes, drugs development
Source: Fletcher R.W., Fletcher S.W.: Clinical Epidemiology. The essentials .Lippincott Williams & Wilkins 2005

TOPICS
Roots of modern epidemiology
Epidemiology among health sciences
Definition of epidemiology
Epidemiological paradigms
Application of epidemiology in medical research
Clinical 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
(Last, 2001)
!

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
surveillance, observation, hypothesis testing, analytic research, and experiments.

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
analysis by person, place and time
„who” – „where” – „when”
?

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
risk factors, protective factors, modyfying factors …

DETERMINANTS (source)
HOST
FACTORS
SOCIO-
ECONOMIC
FACTORS
- Genes
- Gender
- Age
- Poverty
- Employment
- Isolation
ENVIRON-
MENTAL
FACTORS
LIFE STYLE
FACTORS
OTHER
FACTORS
- Air quality
- Water quality
- Occupational environment
- Home environment
- Social environment
- Nutrition
- Physical activity
- Tobacco
- Alcohol
- Drugs
- Sexual activity
Education
- Health care system
- Transport.
- Recreation

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
diseases, causes of death, behavior, reactions to preventive regimens, provision and use of health services …

HEALTH-RELATED PHENOMENA

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
APPLICATION TO CONTROL to assess the public health importance of diseases, identify the population at risk, identify the causes of disease, describe the natural history of disease, and evaluate the prevention and control of disease

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
APPLICATION TO CONTROL health promotion preventive measures diagnostic standards therapeutic standards

EPIDEMIOLOGY versus CLINICAL MEDICINE
PRINCIPAL TASKS
CLINICAL MEDICINE EPIDEMIOLOGY
Diagnosis
Treatment
Prognosis
Epidemiological study
Prevention, health promotion
Risk assessment

EPIDEMIOLOGY
FROM KNOWLEDGE
Descriptive epidemiology (what, who, where ..?)
Analytical epidemiology (why ?)
TO APPLICATION
Prevention
New diagnostic / therapeutic procedures
Refined provision of health services
…

TOPICS
Roots of modern epidemiology
Epidemiology among health sciences
Definition of epidemiology
Epidemiological paradigms
Application of epidemiology in medical research
Clinical epidemiology

Non-random occurrence of diseases
Between-subject variability in health and exposures* leading to co-variability
• - a very broad concept (smoking=exposure; gene variant=exposure; etc..)
& Reliability of the results

DISEASES DO NOT OCCUR BY RANDOM
?
?


    
  
  



?
?
WHY ME ?
NON-RANDOM OCCURRENCE IMPLIES CAUSATION
EXPOSURE TO WHAT ? (HARMFUL AGENTS ? POOR GENES ? … ?)

Q: IS KNOWN HEALTH DISORDER
RELATED TO KNOWN EXPOSURE ?
A: COVARIABILITY – Y/N
(1) Between-subject variability in health status
(2) Between-subject variability in potential risk factors
(1) follows (2) = covariability

Reliable Measurement of Health and Exposure
Evidence of Covariability

SIR DAVID ROXBEE COX
FOUR CHALLENGES:
MEASUREMENT
STUDY DESIGN
DATA ANALYSIS
INTERPRETATION
David R. Cox: Some challenges for medical statistics (symposium „Modern Statistical Methods in Medical Research” - Nobel Foundation Series „Frontiers in Medicine”
< European Journal of Epidemiology 2005;30:5-9 >

LORD KELVIN (1824-1907)
When you can measure what you are speaking about, and express it in numbers, you know something about it.
But when you cannot your knowledge is of a meager and unsatisfactory kind
(Lord Kelvin)

MEASUREMENT
Quantitative scale: blood glucose level …
- Qulitative scale: round opacity on chest xray …
SOURCES
Interview, standardized questionnaire, laboratory tests, composed indices … case definition …

MEASUREMENT - ERRORS
TYPE I: above, above, below, above, below, below, above, below, above, above
TYPE II: either above, above, above, above, above, above, above or below, below, below, below, below, below, below
Repeat measurements and you are close to the true value (average)
RANDOM ERROR
Repeat measurements and you are always one way away from the true value
SYSTEMATIC ERROR
(BIAS)

GOOD EPIDEMIOLOGY PRACTICE
EPIDEMIOLOGICAL STUDY – A MEASURING TOOL
Prevalence of diabetes
Role of sleep deprivation in high blood pressure
Protective significance of face mask in COPD etc., etc.
MEASUREMENT IS SUBJECT TO ERROR

RANDOM ERROR
Divergence – due to chance alone – of an observation
(measurement) on a sample from the true population value
(estimate ≠ parameter). Three sources:
•
Biological variation;
•
Sampling error;
• Measurement error.
Given biological variation and limited accuracy of the measurement random error can be reduced by increasing the size of the sample
( estimate obtained in a sample composed of all candidates = parameter)

SYSTEMATIC ERROR = BIAS
Systematic divergence (either ‘in plus’ or ‘in minus’) of an observation (measurement) on a sample from the true population value (estimate ≠ parameter). Three principal classes of bias:
• Selection bias;
• Information bias;
• Confounding.

SELECTION BIAS
Distortion resulting from the manner in which subjects are selected (from population to sample)
• Berkson’s bias (hospital admission bias): affects studies done in hospitalized populations – the relation found in hospital may not reflect the one in the population;
• Nonresponse bias: „refusers” are more likely to engage in unhealthy behaviors
• Healthy worker effect: seriously ill people are unable to join and remain in the workforce
• …
Way to avoid (minimize) = representative, probability sampling

INFORMATION BIAS
Causes: measurement device defects, inappropriate questionnaires, inaccurate diagnostic procedures,
Result: placement of a subject in a wrong category
(misclassification)
• Recall bias: sick individuals are more likely to recall hazardous exposures, events, etc. (mothers of leukemia children remember all,
mothers of healthy children „do not care”)
• Diagnostic suspicion bias: increased diagnostic attention toward exposed (endometrial cancer versus hormone replacement therapy –
estrogens)
• …

CONFOUNDING
Distortion in an association between a study exposure and disease brought about by the influence of „a third factor”
Confounder:
Is associated with the exposure in question;
Is an independent risk factor for the disease
Confounder
↨
Exposure
→ →
→ ?
Disease
Is not intermediate in the causal pathway: exposure - disease

RANDOM ERROR AND SYSTEMATIC ERROR
True Value of the Studied Event = bull’s eye
Result of the Study = dot
Random Error (Imprecision)
Low High
Systemtic
Error (Bias)
Low
High

VALIDITY
• Internal validity ( state-of-art measurements on sample )
• External validity ( generalizability )

GOOD EPIDEMIOLOGY PRACTICE !

GOOD EPIDEMIOLOGY PRACTICE
Identify potential sources of errors
Avoid errors
Control errors
Adjust for errors

TOPICS
Roots of modern epidemiology
Epidemiology among health sciences
Definition of epidemiology
Epidemiological paradigms
Application of epidemiology in medical research
Clinical epidemiology

EPI CONTRIBUTION TO MEDICAL RESEARCH
I – INVESTIGATION INTO NATURAL HISTORY OF DISEASES
Good
Health 
Subclinical
Changes 
Clinical
Disease 
Death or
Recovery

EPI CONTRIBUTION TO MEDICAL RESEARCH
II – DESCRIPTION OF HEALTH STATUS OF POPULATION
Incidence



According to sex
According to age
According to …
Occurrence of diseases
(health events)

Prevalence



According to sex
According to age
According to …

EPI CONTRIBUTION TO MEDICAL RESEARCH
III – EXPLORATION OF CAUSATION
Genetic factors
Genetic factors
 
Lifestyle factors
 Good
Health

Environmental factors
 Onset of disease
 Ill
Health

Environmental factors
 Lifestyle factors

EPI CONTRIBUTION TO MEDICAL RESEARCH
IV – EVALUATION OF INTERVENTION
Health

Health promotion
Preventive measures
Public health services
Treatment

Ill 
Health
Diagnostic
Procedures

Medical Care

TOPICS
Roots of modern epidemiology
Epidemiology among health sciences
Definition of epidemiology
Epidemiological paradigms
Application of epidemiology in medical research
Clinical epidemiology

EPIDEMIOLOGY and CLINICAL MEDICINE
CLINICAL MEDICINE
Patient
EPIDEMIOLOGY
Population/Group
Treatment Prevention, health
(what is the true effect of the treatment T ?)
Risk assessment
Low level of enzyme E has a prognostic value in patient A and not in patient B
(what is the true diagnostic value of enzyme E ?)

EPIDEMIOLOGY and CLINICAL MEDICINE
CLINICAL MEDICINE EPIDEMIOLOGY
Treatment
Prognosis
Prevention, health
Risk assessment

CLINICAL EPIDEMIOLOGY
The science of making predictions about individual patients by counting clinical events in groups of similar patients and using strong scientific methods to ensure that the predictions are accurate.
The purpose of clinical epidemiology is to develop and apply methods of clinical observation that will lead to valid conclusions by avoiding being misled by systamatic error and the play of chance
Source: Fletcher R.W., Fletcher S.W.: Clinical Epidemiology. The essentials .Lippincott Williams & Wilkins 2005

CLINICAL EPIDEMIOLOGY
„Clinical” because it seeks to answer questions and to guide clinical decisions making with the best available evidence
„Epidemiology” because many of the methods used to answer the questions have been developed by epidemiologists (patient as a member of the population of patients – disease specific)
Source: Fletcher R.W., Fletcher S.W.: Clinical Epidemiology. The essentials .Lippincott Williams & Wilkins 2005

CLINICAL EPIDEMIOLOGY ISSUES
Abnormality
Diagnosis
Frequency
Risk
Prognosis
Treatment
Prevention
Cause
Source: Fletcher R.W., Fletcher S.W.: Clinical Epidemiology. The essentials .Lippincott Williams & Wilkins 2005

FROM CO-EXISTENCE TO SYNERGISM
EPIDEMIOLOGY vs CLINICAL MEDICINE
EPIDEMIOLOGY ↔ CLINICAL MEDICINE