epidemiology and its contribution to medical research (selected slides) jan e. zejda department of...

EPIDEMIOLOGY EPIDEMIOLOGY AND ITS AND ITS

CONTRIBUTION CONTRIBUTION TO MEDICAL RESEARCHTO MEDICAL RESEARCH

(selected slides)(selected slides)

Jan E. Zejda

Department of Epidemiology, Medical University of Silesia

TOPICSTOPICS

Roots of modern epidemiology

Epidemiology among health sciences

Definition of epidemiology

Epidemiological paradigms

Application of epidemiology in medical research

Clinical epidemiology

TOPICSTOPICS

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 CHOLERA CARRIED BY AIR POLLUTED BY MIASMAMIASMA

(miasma = rotting organic matter)(miasma = rotting organic matter)

Farr’s hypothesis („miasma theory”)Deaths due to cholera versus elevation of the residence place in London

0

20

40

60

80

100

120

140

<20 20-40 40-60 60-80 80-100 100-120 340-360

Stopy nad poziomem morza

Zgon

y/10

000

Źródło: Gordis L.: Epidemiology. W.B. Sounders Company, Philadelphia 1996)

Feet above sea level

Deaths

MIASMA THEORYMIASMA THEORY(miasma in Greek = pollution)(miasma in Greek = pollution)

340-360 100-120 80-100 60-80 40-60 20-40 <20

Stopy nad poziomem morza

...

Thickness of miasma layer

Feet above sea level

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.

C2H5OC2H5

CHCl3

↓KidneyLiverHeart

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

LLondonondon

Snow’s statistical argument regarding water-borne disease

Mortality distribution according to the place of residence / source of drinking water

Water Supply Company Number ofhouses

Number ofdeaths

Deaths rate (n/10000 houses)

Southwark&Vauxhall 40 046 1263 315

Lambeth 26 107 98 37

Source: Fox J.P. et al.: Epidemiology. Man and Disease. The Macmillan Company, London 1970)

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

LLondonondon

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

LLondonondon

SNOW’S DISTINCT METHODSSNOW’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 MESSAGEIMPORTANT MESSAGE

Cholera put under control long before

the causative agent was discoveredresponse

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

Koch – 1884 !

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

EPIDEMIOLOGY TODAYEPIDEMIOLOGY TODAY(from infectious to non-infectious diseases)(from infectious to non-infectious diseases)

Ch. Niezakaźne

Ch. Zakaźne

√ ADVANCES IN MEDICINE

√ DEMOGRAPHY

√ QUALITY OF LIFE …

↑ YESTERDAY TODAY ↑

Non-infectious diseases

Infectious diseases

TOPICSTOPICS

Roots of modern epidemiology

Epidemiology among health sciences

Definition of epidemiology

Epidemiological paradigms

Application of epidemiology in medical research

Clinical epidemiology

HEALTH SCIENCESHEALTH 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 SCIENCESHEALTH 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

TOPICSTOPICS

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)

!

DEFINITION OF DEFINITION OF EPIDEMIOLOGYEPIDEMIOLOGY

EPIDEMIOLOGYEPIDEMIOLOGYThe 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

STUDYsurveillance, observation, hypothesis

testing, analytic research,

and experiments.

EPIDEMIOLOGYEPIDEMIOLOGYThe 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

DISTRIBUTIONanalysis by person, place and time

„who” – „where” – „when”?

EPIDEMIOLOGYEPIDEMIOLOGYThe 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

DETERMINANTS (function)risk factors, protective factors,

modyfying factors …

HOST FACTORS

SOCIO-ECONOMIC

FACTORS

ENVIRON-MENTALFACTORS

LIFE STYLEFACTORS

OTHERFACTORS

- Genes- Gender

- Age

- Poverty- Employment

- Isolation

- Air quality - Water quality

- Occupational environment

- Home environment

- Social environment

- Nutrition- Physical activity- Tobacco- Alcohol- Drugs

- Sexual activity

-Education-- Health care

system- Transport.- Recreation

DETERMINANTS (source)DETERMINANTS (source)

EPIDEMIOLOGYEPIDEMIOLOGYThe 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

HEALTH RELATED STATES OR EVENTS

diseases, causes of death, behavior,reactions to preventive regimens,

provision and use of health services …

HEALTH-RELATED PHENOMENA

EPIDEMIOLOGYEPIDEMIOLOGYThe 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 CONTROLto 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

EPIDEMIOLOGYEPIDEMIOLOGYThe 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 CONTROLhealth promotion

preventive measuresdiagnostic standards

therapeutic standards

EPIDEMIOLOGY versus CLINICAL EPIDEMIOLOGY versus CLINICAL MEDICINEMEDICINE

PRINCIPAL TASKSPRINCIPAL TASKS

CLINICAL MEDICINE EPIDEMIOLOGY

Diagnosis Epidemiological study

Treatment Prevention, health promotion

Prognosis Risk assessment

EPIDEMIOLOGYEPIDEMIOLOGY

FROM KNOWLEDGEDescriptive epidemiology (what, who, where ..?)Analytical epidemiology (why ?)

TO APPLICATIONPreventionNew diagnostic / therapeutic proceduresRefined provision of health services…

TOPICSTOPICS

Roots of modern epidemiology

Epidemiology among health sciences

Definition of epidemiology

Epidemiological paradigms

Application of epidemiology in medical research

Clinical epidemiology

EPIDEMIOLOGIC PARADIGMSEPIDEMIOLOGIC PARADIGMS

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 DISEASES DO NOT OCCUR BY RANDOMRANDOM

WHY ME ?NON-RANDOM OCCURRENCE IMPLIES CAUSATION

EXPOSURE TO WHAT ? (HARMFUL AGENTS ? POOR GENES ? … ?)

?

?

?

?

(1) Between-subject variability in health status

(2) Between-subject variability in potential risk factors

(1) follows (2) = covariability

Q: IS KNOWN HEALTH DISORDER Q: IS KNOWN HEALTH DISORDER

RELATED TO KNOWN RELATED TO KNOWN EXPOSURE ?EXPOSURE ?

A: COVARIABILITY – Y/NA: COVARIABILITY – Y/N

Reliable Measurement of Health and Exposure

Evidence of Covariability

SIR DAVID ROXBEE COX 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)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 unsatisfacto

ry kind (Lord

Kelvin)

MEASUREMENTMEASUREMENT

- Quantitative scale: blood glucose level …

- Qulitative scale: round opacity on chest x-ray …

SOURCES

Interview, standardized questionnaire, laboratory tests, composed indices … case definition …

MEASUREMENT - ERRORSMEASUREMENT - 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 Repeat measurements and you

close to the true value (average) are always one way away from

the true value

RANDOM ERROR SYSTEMATIC ERROR (BIAS)

GOOD EPIDEMIOLOGY PRACTICEGOOD 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 ERRORRANDOM 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 = SYSTEMATIC ERROR = BIASBIAS

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 BIASSELECTION 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 BIASINFORMATION 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)

• …

CONFOUNDINGCONFOUNDING

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 → →↨ Disease

Exposure → ?

Is not intermediate in the causal pathway: exposure - disease

RANDOM ERROR AND SYSTEMATIC RANDOM ERROR AND SYSTEMATIC ERRORERROR

True Value of the Studied Event = bull’s eyeResult of the Study = dot

Random Error (Imprecision)

Low High

LowSystemticError (Bias)

High

VALIDITYVALIDITY

• Internal validity (state-of-art measurements on sample)

• External validity (generalizability)

GOOD EPIDEMIOLOGY PRACTICE !GOOD EPIDEMIOLOGY PRACTICE !

GOOD EPIDEMIOLOGY PRACTICEGOOD EPIDEMIOLOGY PRACTICE

Identify potential sources of errors

Avoid errors

Control errors

Adjust for errors

TOPICSTOPICS

Roots of modern epidemiology

Epidemiology among health sciences

Definition of epidemiology

Epidemiological paradigms

Application of epidemiology in medical research

Clinical epidemiology

Core ContributionsCore Contributions

1,2,3,41,2,3,4

EPI CONTRIBUTION TO MEDICAL EPI CONTRIBUTION TO MEDICAL RESEARCHRESEARCH

I – INVESTIGATION INTO NATURAL HISTORY OF DISEASES

Good Health

Subclinical Changes

Clinical Disease

Deathor

Recovery

Incidence

According to sexAccording to ageAccording to …

Occurrenceof diseases

(health events)

Prevalence

According to sexAccording to ageAccording to …

EPI CONTRIBUTION TO MEDICAL EPI CONTRIBUTION TO MEDICAL RESEARCHRESEARCH

II – DESCRIPTION OF HEALTH STATUS OF POPULATION

Genetic factors

Genetic factors

Lifestyle factors

Good Health

Onset of

disease

Ill Health

Lifestyle factors

Environ-mental factors

Environ-mental factors

EPI CONTRIBUTION TO MEDICAL EPI CONTRIBUTION TO MEDICAL RESEARCHRESEARCH

III – EXPLORATION OF CAUSATION

Treatment

Good Health

← ← ← Ill Health

DiagnosticProcedures

Health promotionPreventive measuresPublic health services

Medical Care

EPI CONTRIBUTION TO MEDICAL EPI CONTRIBUTION TO MEDICAL RESEARCHRESEARCH

IV – EVALUATION OF INTERVENTION

TOPICSTOPICS

Roots of modern epidemiology

Epidemiology among health sciences

Definition of epidemiology

Epidemiological paradigms

Application of epidemiology in medical research

Clinical epidemiology

EPIDEMIOLOGY and CLINICAL EPIDEMIOLOGY and CLINICAL MEDICINEMEDICINE

CLINICAL MEDICINE EPIDEMIOLOGY

Patient Population/Group

Treatment Prevention, health promotion

Prognosis Risk assessment

HOWEVER

Patient A responds to the treatment T, patient B does not, and patient C …

(what is the true effect of the treatment T ?)

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 EPIDEMIOLOGY and CLINICAL MEDICINEMEDICINE

CLINICAL MEDICINE EPIDEMIOLOGY

Treatment Prevention, health promotion

Prognosis Risk assessment

CLINICAL EPIDEMIOLOGY

CLINICAL EPIDEMIOLOGYCLINICAL 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 chanceSource: Fletcher R.W., Fletcher S.W.: Clinical Epidemiology. The

essentials .Lippincott Williams & Wilkins 2005

CLINICAL EPIDEMIOLOGYCLINICAL 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 ISSUESCLINICAL 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 SYNERGISMFROM CO-EXISTENCE TO SYNERGISM

EPIDEMIOLOGY vs CLINICAL MEDICINE

EPIDEMIOLOGY ↔ CLINICAL MEDICINE