INTRODUCTION TO EPIDEMIOLOGY

INTRODUCTION TO EPIDEMIOLOGY

DR. MAHESWARI JAIKUMAR

DEFINITION“That branch of medical science which treats epidemics" (Parkin.1873)

“

The science of the mass phenomena of infectious diseases”. (Frost, 1927)

“The study of disease, any disease, as a mass phenomenon.” (Greenwood.1934)

“The study of the distribution & determinants of disease frequency in man”(Mac Mohan,1960)

(John M Last,1988)

“The study of the distribution & determinants of health related states or events in specified populations and the application of this study to control of health problems”.

COMPONENTS OF EPIDEMIOLOGY

DISEASE FREQUENCY.

DISTRIBUTION OF DISEASE.

DETERMINANTS OF DISEASE.

DISEASE FREQUENCYRefers to the measurement of health related event in the form of rates & ratios.

E.g.. Prevalence rate, Incidence rates, Death rate etc.

These rates are essential for comparing the disease frequency in different populations or sub groups of the same population

Such comparison yield valuable information on disease etiology.

This is a vital step in the development of strategies for prevention of control of health problems.

DISTRIBUTION OF DISEASE

The basic tenet of epidemiology is that the distribution of disease occurs in patterns in a community.

An important function is to study the pattern of the distribution in various subgroups

Thus epidemiology examines whether there has been an increase or decrease over time span.

An important outcome of this step is formulation of etiological hypothesis

DETERMINANTS OF DISEASE

This aspect of epidemiology is known as “analytical epidemiology”.

Analytical strategies help in developing scientifically sound health programmes, interventions & policies.

AIMS OF EPIDEMIOLOGY

INTERNATIONAL EPIDEMIOLOGICAL ASSOCIATION (IEA)To describe the distribution & magnitude of health & disease problems in human populations.

To identify etiological factors (Risk Factors)in the pathogenesis of disease

To provide the data essential to the planning, implementation & evaluation of services for the prevention, control & treatment of disease & to the setting up of priorities among those services.

THE ULTIMATE AIMTo eliminate or reduce the health problem or it’s consequences.

To promote the health & well being of society as a whole.

EPIDEMIOLOGICAL APPROACHAsking questions.

Making comparison.

ASKING QUESTIONS

QUESTIONS RELATED TO HEALTH EVENTS.

QUESTIONS RELATED TO HEALTH ACTION.

RELATED TO HEALTH EVENTSWhat is the event? ( The problem).

What is the magnitude?Where did it happen ?When did it happen?Who are affected?Why did it happen?

RELATED TO HEALTH ACTIONWhat can be done to reduce this problem and its consequences?

How can it be prevented in future?

What action should be taken by the community? By whom these activities be carried out?

What resources are required? How are the activities to be organized?

What difficulties might arise, & how might they be overcome?

MAKING COMPARISIONThe basic approach in epidemiology is

to make comparison & draw inferences.

This may be comparison of two or more groups.

The first consideration before making .

comparison is to the “comparability”.Matching or randomization helps in

ensuring comparability.

MEASUREMENTS IN EPIDEMIOLOGY

Measurements of mortality.

Measurements of morbidity.

Measurements of disability.

Measurements of natality.

Measurement of the presence, absence or distribution of the characteristic or attributes of the disease.

Measurement of medical needs, health care facilities, utilization of health services & other related events.

Measurement of the presence, absence or distribution of the environmental & other factors suspected of the environmental & other factors suspected of causing the disease.

Measurement of demographic variables.

TOOLS OF MEASUREMENTThe epidemiologist usually expresses disease magnitude as a RATE, RATIO OR PROPORTION.

RATEA rate measures the occurrence

of some particular event in a population during a given time period.

DEATH RATE = Number of deaths in a year *1000

MID YEAR POPULATION

A RATE COMPRISES THE FOLLOWING ELEMENTS.

Numerator,Denominator,Time Specification ,And a Multiplier

CATEGORIES OF RATECRUDE RATES : OR

UNSTANDARDIZED RATES. Eg : Birth rates, Death rates.

SPECIFIC RATES : Actual observed rates due to specific causes during specific time periods.Eg: Tuberculosis – Annual, monthly rates.

STANDARDIZED RATES : These are obtained by direct or indirect method of standardization.Eg: Age & Sex standardized rate.

RATIO It expresses a relation in size

between two random quantities. The numerator is not a part of

the denominator.Ratio is the result of dividing

one quantity by another.RATIO = x : y or x

y

E.g. : The number of children with scabies at a certain time :

The number of children with malnutrition at a certain time

PROPORTIONA Proportion is a ratio which indicates the relation in magnitude of a part of the whole.

The numerator is always included in the denominator.

A proportion is usually expressed in percentage.

E.g. The number of children with scabies at a certain time *100The total number of children in the village at the same time

MORTALITY RATES & RATIOSCrude Death Rates.Specific Death Rates.Case Fatality Rates.Proportional Mortality Rates.

Survival Rates.Adjusted or Standardized Rates.

MEASUREMENTS OF MORBIDITY

Incidence.Prevalence.

INCIDENCE.The number of new cases occurring in a defined population during a specified period of time.

INCIDENCE =

Number of new cases of specific disease during a given period

Population at risk during that time *1000

Incidence Rate : Refers to

Only to new cases.During a given period (one

year).In a specified population or

“population at risk”, unless other denominators are chosen.

It can refer to new spells or episodes of disease arising.

Incidence measures the rate at which new cases are occurring in a population.

USES IF INCIDENCE RATES

The incidence rates are health status indicator. It is useful for taking action.

To control disease.For research into etiology.For research into pathogenesis,

distribution of disease & efficacy of preventive & therapeutic measures.

Provides useful insights into the effectiveness of the health services provided.

PREVALENCEPrevalence refers to ALL CURRENT cases (Old & New) existing at a given point of time, or over a period of time in a given population.

It is actually a ratio

TYPES OF PREVALENCEPOINT PREVALENCE.

PERIOD PREVALENCE.

POINT PREVALENCE

Point Prevalence is defined as the number of all current cases (old & new) of a disease at one point of time, in relation to a defined population.

FORMULA

PP = Number of all current cases (old

& new) of a specified disease existing at a given point in time.

PERIOD PREVALENCEIt measures the frequency of all current cases ( old & new ) existing during a defined period of time. (Annual prevalence).

It includes cases arising before but extending into or through to the year as well those cases arising during the year.

FORMULANumber of existing cases (old

& new) of a specified disease during a given period of time interval

Estimated mid interval population at risk

X100

DIAGRAMMATIC REPRESENTATION

Case 2 Case 3 Case 4

Case 5

Case 7 Case 6

Case 8

Dec 31Jan 1

Case 1

Incidence : case 3,4,5 & 8. Point prevalence Jan 1 : 1,2 & 7. Point prevalence Dec 31 : 1,3,5 & 8. Period prevalence (Jan – Dec) 1,2,3,4,5,7 & 8

RELATIONSHIP BETWEEN INCIDENCE & PREVALENCE

Prevalence depends upon : 1.

Incidence. 2.

Duration of illness.FORMULA : P = I * D I = INCIDENCE D= MEAN DURATIONTherefore : I = P/D D= P/I

DIAGRAMATIC REPRESENTATION

DESCRIPTIVE EPIDEMIOLOGY

Descriptive studies are usually the first phase of an epidemiological investigation.

These studies are concerned with observing the distribution of disease or health – related characteristics in human populations.

Such studies basically ask the questions.

When is the disease occurring?

Where is it occurring?Who is getting the disease?

PROCEDURES IN DESCRIPTIVE

STUDIESDefining the population to be

studied.Defining the disease to be

studied.Describing the disease by --- TIME,

PLACE & PERSON.Measurement of disease.Comparing with known indices.Formulation of an aetiological

hypothesis

1.DEFINING THE POPULATION

Descriptive studies are investigations of populations.

Therefore the first step is to define the “population base” in terms of total number, & also by composition in terms of age , sex, occupation, cultural characteristics & similar other information.

The “defined population” can be the whole population in a geographic area or a representative taken from it.

The defined population should be large enough so that the specific rates are meaningful.

The community chosen should be stable & not migratory.

2.DEFINING THE DISEASE UNDER STUDIES

The epidemiologist looks for an operational definition.

Operational definition spells out the criteria by which the disease can be measured.

Once operational definition is established, it should be maintained through the study.

3.DESCRIBING THE DISEASE

Disease is described by person, place & time distribution.

CHARACTERISTICS EXAMINED IN DESCRIPTIVE STUDIESTIME PLACE PERSON

Year, Season

Climatic zones

Age, Birth order

Month, Week

Country, region

Sex, Family size

Day, Hour of onset

Urban/ rural / Local community

Marital State, Height, Weight

Duration Towns, Cities, Institutions

Occupation, Social status, Education, Blood pressure, Blood cholesterol, Personal habits

TIME DISTRIBUTION

The pattern of a disease may be described by the time of occurrence.

Whether it shows periodic increase?

Whether it follows a consistent trend?

Epidemiologists have identified three kinds of time trends or fluctuations in disease occurrence.

SHORT TERM FLUCTUATIONS.

PERIODIC FLUCTUATION.

LONG – TERM or SECULAR TRENDS

SHORT TERM FLUCTUATIONS

The best known short term fluctuation in the occurrence of disease is an epidemic.

Epidemic is defined as : the occurrence in a community or region of cases of an illness or other related events clearly in excess of normal expectancy”

TYPES OF EPIDEMICS

A. Common Source Epidemics.

B. Propagated Epidemics.

C. Slow (or) Modern Epidemics.

COMMON SOURCE

EPIDEMICSSingle Exposure or “POINT SOUIRCE” epidemics.

Continuous or “MULTIPLE EXPOSURE EPIDEMICS”

A graph of the time distribution of epidemic cases is called the “EPIDEMIC CURVE”

An epidemic curve may suggest, 1. Time relationship with

exposure to a suspected source.

2. A Cyclical or Seasonal pattern suggestive of a particular infection

EPIDEMIC CURVE

TIME

NUMBER OF CASES

EXPOSURE

COMMON SOURCE

EPIDEMICS These are also known as “point Source”

epidemics. The exposure to the disease agent is brief &

essentially simultaneous, the resultant cases all develop within one incubation period of the disease. They are of two types :

1. Common Source Single Exposure Epidemics.

2. Common Source Continuous or Repeated exposure.

COMMON SOURCE SINGLE EXPOSURE EPIDEMICThe exposure to the disease agent is brief & essentially simultaneous, the result cases all develop within one incubation period of the disease.

E.g., An epidemic of food poisoning

EPIDEMIC CURVE

TIME

NUMBER OF CASES

EXPOSURE

Common Source Single Exposure Epidemic curve usually has one peak.

One point of interest is the “median incubation period”.

It is the time required for 50 per cent of the cases to occur following exposure.

MAIN FEATURES –POINT SOURCE EPIDEMIC

The epidemic curve rises & falls rapidly , with no secondary waves.

The epidemics tends to be explosive.

There is clustering of cases over a narrow interval of time.

All the cases develop within one incubation period of disease.

Common source epidemics are frequently, but not always due to exposure to an infectious agent.

They can result from contamination of the environment (air, water, food, soil) by industrial chemicals or pollutants, E.g., Bhopal gas tragedy in India & Minamata disease in Japan resulting from consumption of fish containing high concentration of methyl mercury

If the epidemic continues over more than one incubation period, there is either a continuous or multiple exposure to a common source, or a propagated spread.

COMMON SOURCE CONTINUOUS OR REPATED EPIDEMICSSome times the exposure from the

same source may be prolonged – continuous or repeated or intermittent – not necessarily at the same time or place.

A prostitute may be a common source on gonorrhea outbreak, but since she will infect her clients over a period of time there may be no explosive rise in the number of cases.

A well of contaminated water or a nationally distributed brand of vaccine or food could result in similar outbreaks.

The outbreak continued beyond the range of one incubation period.(1976 –Legionnaire’s disease)

There was no evidence of secondary cases among persons who had contact with ill persons.

Water borne cholera is a familiar example, the epidemic reaches a sharp peak, but tails off gradually over a longer period of time.

PROPAGATED EPIDEMICS

A propagated epidemic is most often of infectious origin & results from person to person transmission of an infectious agent.

The epidemic usually shows a gradual rise & tails off over a much longer time.

Transmission continues until the number of susceptibles is depleted or susceptible individuals are no longer exposed to infected persons or intermediary vectors.

The speed of spread depends upon herd immunity, opportunities for contact & secondary attack rate.

Propagated epidemics are more likely to occur where there is a regular supply of new susceptible individuals lowering herd immunity.

TYPICAL PROPAGATED EPIDEMIC

INITIAL EPIDEMIC HEIGHT OF EPIDEMIC

TERMINATION OF EPIDEMIC

PERIODIC FLUCTUATIONTwo types of periodic

fluctuation may be described.

1. SEASONAL TREND.

2. CYCLIC TREND.

SEASONAL TREND

Seasonal trend is a well known trend in many communicable disease measles, varicella, malaria.

Measles is usually at its height in early spring.

Bacterial gastrointestinal infections are prominent in summer months because of warm weather & rapid multiplication of flies.

CYCLIC TRENDSome disease occur in cycles

spread over short periods of time which may be days, weeks, months or years..

E.g., Rubella occurred every 6-9 years.

This is due to naturally occurring variations in herd immunity.

A build up of susceptible is again required in the herd before there can be another attack.

Influenza pandemics are known to occur at intervals of 7-10 years due to antigenic variations.

LONG TERM OR SECULAR TRENDSThe term “secular trends”

implies changes in the occurrence of disease over a long period or time, generally several years or decades.

Secular trend implies a consistent tendency to change in a particular direction or a definite movement in one direction.

E.g., Coronary heart disease, lung cancer have shown consistent upward trend in the developed countries during the past 50 years.

PLACE DISTRIBUTIONStudy of the geography of the

disease (geographical pathology)is one of the important dimensions of descriptive epidemiology.

With the geographical pathology we gain perspective on the fascinating differences in disease patterns between two geographical areas.

The relative importance of genes versus environment; changes with migration; the possible role if diet & other etiological factors.

Geographical diseases have profoundly influenced our understanding of disease, its nature, its detriments & its relation to subsequent pathology.

The geographic variation in disease occurrence has been one of the stimulants to national & international studies.

The world is not a uniform unit.

Cultures, standard of living & external environments vary greatly. The use of migrant studies is one way to distinguishing genetic & environmental factors.

Geographic patterns provide an important source of clues about the causes of the disease. The geographic variations may be classified as :

1. International variations. 2. National variations. 3. Rural – Urban differences. 4. Local distributions

INTERNATIONAL VARIATIONSThere is a marked

international differences in the occurrence of various disease. This variations have stimulated epidemiologists to search for cause – effect relationships between the environmental factors & disease.

The aim is to identify factors which are crucial in the cause & prevention of disease

E.g., Cancer of the oral cavity & uterine cervix are exceedingly common in India as compared to industrialized countries.

There is marked difference between the incidence of each cancer in different parts of the world. It is common in Japan, but unusual in USA.

NATIONAL VARIATIONS

Variations in disease occurrence also exist within countries or national boundaries.

Distribution of lathyrism, endemic goitre, flurosis, leprosy, malaria, nutritional deficiency diseases have all shown variations in their distribution in India, with some part of the country more affected than the others.

RURAL – URBAN VARIATIONS

Rural \ Urban variations are well known.

Chronic bonchitis, lung cancer, cardio vascular diseses, mental illness & drug dependence are usually more frequent in in urban areas than in rural areas.

On the other hand, skin & zoonotic diseases & soil transmitted helminths may be more frequent in rural areas than in urban areas.

Death rates especially maternal mortality rates are higher for rural than urban areas.

These variations may be due to variations in population density, social class, deficiencies in health services, levels of sanitation, education & environmental factors.

The epidemiologists seek to define groups which are at higher risk for a particular diseases, and provides guidelines to the health administrator for their prevention & control.

LOCAL DISTRIBUTIONS

Inner & outer city variations are common.

These variations are best studied with the aid of “spot maps” or “shaded maps”.

These maps show at a glance areas of high or low frequency, the boundaries & patterns of disease distribution.

If the map shows “clustering” of cases , it may suggest a common source of infection or a common risk factor shared by all cases. E.g., John Snow’s cholera epidemic.

Geographic differences in

disease occurrence is an important dimension of a descriptive study. These differences are determined by the agent, host & environmental factors.

MIGRATION STUDIES

Large scale migration of human population from one country to another provides a unique opportunity to evaluate the role of the possible genetic & environmental factors in the occurrence of disease in a population. Migration studies can be carried out in two ways :

1. Comparison of disease & death rates for migrants with those of their kin who have stayed at home.

2. Comparison of migrants with local population of the host country provides information on genetically different groups living in a similar environment.

PERSON DISTRIBUTION

In descriptive studies disease is further characterized by defining the persons who develop the disease by age, sex, occupation, marital status, habits, social class & other host factors.

These host factors help us to understand the natural history of disease.

AGEAge is strongly related to

disease than other host factors.

Certain factors are more frequent in certain age groups than others.

E.g., Measles in childhood, cancer in middle age & atherosclerosis in old age.

Many chronic degenerative diseases show an increasing in the prevalence with advancing age.

BIO MODALITYSome times there may be two

separate peaks instead of one in the age incidence curve of a disease as in the case of Hodgkin’s disease, leukaemia & female breast cancer.

This phenomenon is known as bio modality.

This suggests that two set of causal factors might be operative.

0 10 20 30 40 50 60 70 80

765 4 3 21 0

incidence

GENDERGender is another host

characteristics which is often studied in relation disease using indices such as sex – ratio, sex specific morbidity & mortality rates.

It has been found that certain chronic diseases such as diabetes, hyperthyroidism & obesity are strikingly more common in women than in men & lung cancer & CHD are less frequent in women

Variations in disease frequency between sexes have been ascribed to 1. biological differences including sex linked genetic inheritance & 2. cultural & behavioral differences between sexes (smoking, alcohol, automobile use).

ETHNICITYDifferences in disease

occurrence have been noted between population subgroups of different racial & ethnic origin.

These include tuberculosis, essential hypertension, coronary heart disease, cancer, & sickle cell anemia.

MARITAL STATUSStudies related to marital status reveal that mortality rates were always lower for married males & females than for the unmarried, of the same age & sex.

Marital status can be a risk factor for some disease & conditions.

The observation that cancer cervix is rare in nuns led to the hypothesis regarding marital status & cancer cervix.

Further studies led to the suggestions that cancer cervix may be associated with multiple sexual contacts & promiscuity.

OCCUPATIONIt is now recognized that

man’s occupation has an important bearing on his health status.

Occupation may alter the habit pattern of an employee e.g., sleep, alcohol, smoking, night shifts, etc.

It is obvious that persons working in a particular occupations are exposed to particular types of risk.

Workers on coal mines are more likely to suffer from silicosis, those in sedentary occupations face the risk of heart disease.

SOCIAL CLASSEpidemiological studies have shown that health & illness are not equally distributed in social classes.

Individuals in the upper social classes have long life & better nutritional status than those in the lower social groups.

Certain diseases like CHD, hypertension, diabetes have shown a higher prevalence in upper classes than in lower classes.

Social class differences have also been observed in mental illness & utilization of medical & health care services.

BEHAVIOURHuman behavior is increasingly

looked upon as a risk factor in modern day disease such as coronary heart diseases, obesity & accidents.

The behavioral factors which have attracted the greatest attention are cigarette smoking, sedentary life, over eating & drug abuse.

Mass movement of people such as pilgrimages lend themselves to the transmission of infectious diseases

STRESSStress has been shown to affect a variety of variables related to patients response, e.g., susceptibility to disease, exacerbation of symptoms, compliance with medical regimen, etc.

MIGRATION In India diseases like leprosy,

filaria & malaria are considered to be rural problems.

Because of the movement of people from rural to urban areas these diseases have created a serious problem in urban areas also.

Human movement can be classified as 1. short term, long term & permanent, 2. according to age, sex, occupation, 3. internal or external, 4. urban versus rural.

4. MEASUREMENT OF DISEASE It is mandatory to have a knowledge on

the disease load in the community.

This information should be available in terms of mortality, morbidity, disability & incidence & prevalence so on.

Incidence can be obtained from longitudinal studies & prevalence from cross sectional studies.

CROSS SECTIONAL STUDIESAre simplest form of an

observational studies.

It is based on a single examination of a cross section of population at one point of time.

Cross sectional studies are also known as prevalence studies.

Cross sectional studies are more useful for chronic diseases

Cross sectional diseases provide very little information about the natural history of the disease or about the occurrence of new cases.

LONGITUDINAL STUDIES

In longitudinal studies observations are repeated in the same population over a prolonged period of time by means of follow up examinations.

Cross sectional studies have been likened to a photograph, & longitudinal studies to a cine film

Longitudinal studies are useful :1. To study the natural history

of a disease & its future outcome.

2. For identifying risk factors of a disease.

3. For finding out incidence rates or occurrence of new cases in the community.

Longitudinal diseases are more difficult to organize & more time consuming

COMPARING WITH KNOWN INDICESThe essence of epidemiology is to

make comparisons & ask questions.

By making comparisons between different populations & sub groups of the same population, it is possible to arrive at clues to disease aetiology.

We can also identify the at risk group

FORMULATING HYPOTHESIS

A hypothesis is a supposition, arrived at from observation or reflection.

It can be accepted or rejected using the techniques of analytical epidemiology.

A hypothesis should specify the following :

1. The population.2. The specific cause being

considered.3. Expected outcome –

disease.4. Time response

relationship.

USES OF DESCRIPTIVE STUDIESProvide data regarding the

magnitude of the disease load & types of disease problems in the community in terms of morbidity & mortality rates.

Provide clues to disease aetiology.

Provide background data for planning, organizing & evaluating preventive & curative services.

Contribute to research by describing variations in disease occurrence by time, place & person.

ANALYTICAL EPIDEMIOLOGYIn contrast to the descriptive studies (

the focus is on the population on the whole), the analytical studies focus on individual within the population.

Analytical studies comprise of two distinct types of observational studies.

1. Case Control Studies.2. Cohort studies.

ANALYTICAL EPIDEMIOLOGY

Case control studies

Cohort studies•Individuals with particular disease --- Cases•Individuals without particular disease ---Controls

PROSPECTIVE COHORT STUDY

Presence or absence of a particular disease

TIME

Factor(s) present / Absent

Individual exposed to particular (s) / individual unexpected to particular factor(s)

CASE CONTROL STUDTY

Case control studies is often called “retrospective studies”.

This is the first approach to test causal hypothesis.

The case control method has three distinct features.

Both exposure & outcome (disease) have occurred before the start of the study.

The study proceeds backwards from effect to cause.

It uses a control or comparison group to support or refute an inference.

STEPS IN CASE CONTROL STUDIES

Selection of cases & control.

Matching.

Measurement of exposure.

Analysis & interpretation.

SELECTION OF CASES & CONTROLSSELECTION OF CASES :Definition of a case is crucial to a case

control study. It involves two specifications.1.

Diagnostic criteria. 2. Eligibility criteria.

DIAGNOSTIC CRITERIA : Specifies the diagnostic criteria & the stage of the disease.

ELIGIBILITY CRITERIA : Only newly diagnosed individuals with in specified time are eligible.

SELECTION OF A CASES

The sources may be drawn from, 1. Hospitals.2.General Population.HOSPITALS : It is convenient to

select from hospitals or network of hospitals, admitted during a specified period of time.

GENERAL POPULATION : In a population based study all cases within in a defined geographic area are included (entire cases or randomly selected)

SELECTION OF CONTROLS

The controls must be free from the disease under study.

They must be similar to the cases as possible, except for the absence of the disease under study.

Selection of an appropriate control group is an important pre requisite, for it is against this we will be making comparisons.

SOURCES OF CONTROLS1.Hospital controls.2.Relatives.3.Neighbourhood controls.

4.General population.

MATCHINGThe controls may differ from the

cases in a number of factors such as age, gender, occupation, social status, etc.

An important consideration is to ensure comparability between cases & controls.

This involves what is known as “MATCHING”

Matching is defined is to ensure comparability between cases & controls in such a way that they are similar to cases with regard to certain pertinent selected variables e.g. age, which are known to influence the outcome of the disease, or distort or confound the results.

CONFOUNDING FACTOR

A confounding factor is defined as one which is associated both with exposure & disease, & is distributed unequally in study & control groups.

MEASUREMENT OF EXPOSUREThis may be obtained by interviews, by questionnaires or by studying past records of cases & controls -hospital records, employment records.

ANALYSISThe final step is analysis, to find

out :

1. Exposure rates among cases & controls to suspected factor.

2.Estimation of disease risk associated with exposure ( odds ratio )

CONTINGENCY TABLE

Cases (with Ca lung )

Controls (without Ca lung )

Smokers ( < 5 cigarettes a day )

33 (a) 55 (b)

Non smokers

2 (c) 27 (d)

Total 35 (a+c) 82 (b+d)

EXPOSURE RATE CASES = a

a+c

= 33 / 35 = 94.2 %

CONTROLS = b/(b+d) =55/82 = 67 %

ESTIMATION OF RISKThe second analytical step is

estimation of disease risk associated with exposure.

The estimation of disease risk associated with exposure is obtained by an index known as the “Relative Risk” (RR) or “Risk Ratio”, which is defined as the ratio between the incidence of disease among exposed persons & incidence among non exposed.

It is given by the formula :

Relative Risk = Incidence among exposed

Incidence among non exposed

= a/(a+b) c/(c+d)

ODDS RATIO

Odds Ratio (OR) is the measure of the strength of the association between risk factor & outcome.

The odds ratio is the cross product of the entries in table.

Exposed

Not exposed

Disease

Yes

No

a

c

b

d

Odds Ratio = ad/bc = 33 x 27 55 x 2

= 8.1

Odds ratio is a key parameter in the analysis of case control studies

ADVANTAGESRelatively easy to carry out.Rapid & expensive.Suitable to investigate rare

diseases.No risk to subjects.Allows the study of several

different aetiological factors.Risk factors can be identified.No attrition problems.Ethical problems minimal

DISADVANTAGESProblems of bias relies on

previous records.Selection of an appropriate

control group may be difficult.We cannot measure incidence,&

can only estimate the relative risk.

Do not distinguish between causes & associated factors.

Not suited to evaluation of therapies.

Representativeness is a major concern in case of both cases & controls.

COHORT STUDYCohort study is a type of

analytical study.

Cohort study is known by a variety of names: prospective study, longitudinal study, incidence study & forward looking study.

INDICATIONS FOR COHORT STUDYWhen there is a good

evidence of an association between exposure & disease.

When exposure is rare, but incidence is high among the exposed.

When attrition of the study population can be minimized.

When ample funds are available.

FRAME WORK

Exposed

Not exposed

Disease

Yes

No

a

c

b

d

Total

a + bc + d

TYPES OF COHORT STUDY

Prospective cohort study.

Retrospective cohort study.

Combined of retrospective & prospective cohort study

COHORT STUDY

The elements of cohort study are :

1.Selection of study subjects.

2.Obtaining data on exposure.

3.Selectionof comparison group.

4.Follow up.5.Analysis.

1.SELECTION OF STUDY SUBJECTSThe subjects of cohort study are

selected from general population or select groups within the population.

GENERAL POPULATION:When the exposure or cause of

death is fairly frequent in the population, cohorts may be assembled from the general population.

If the population is large appropriate sample is taken from the population

SPECIAL GROUPS :These may be special groups

that can readily be studied.(select groups – these may be professional groups; doctors, nurses, lawyers, college alumni, government employees, volunteers, etc.

These groups are usually homogenous population

EXPOSURE GROUPS :If the exposure is rare, an

economical procedure is to select a cohort of persons known to have experienced the exposure.

2.OBTAINING DATA ON EXPOSURE

Information about exposure may be obtained from :

1.COHORT MEMBERS-personal interviews, mailed questionnaires.

2.REVIEW OF RECORDS3.MEDICAL

EXAMINATION/SPECIAL TESTS.4.ENVIRONMENTAL SURVEYS

Information about exposure should be collected in a manner that will allow classification of cohort members:

1. according to whether or not they have been exposed to the suspected factor.

2. according to the level or degree of exposure, in the case of special exposure groups.

TABLE. 1

Classification of exposure (cigarettes)

No of deaths

Death rate

½ pack1/2 – 1 pack1 -2 pack2 packs +

24 84 90 97

95.2 107.8 229.2 264.2

3.SELECTION OF COMPARISON GROUPS

Comparison may be :

1.Internal Comparison.2.External comparison.3.Comparison with the general population

INTERNAL COMPARISON :The comparison groups are in

built.Single cohorts enter the study &

its members may, on the basis of information obtained, be classified into several comparison groups according to the degree or levels of exposure to risk (table - 1)

EXTERNAL COMPARISON :When information on degree of

exposure is not available, it is necessary to put up an external control, to evaluate the experience of the exposed group.

E.g., smokers with non smokers, cohort of radiologist compared with ophthalmologist.(The study & control cohorts should be similar in demographic & possibly important variables, other than those under study)

COMPARISON WITH GENERAL POPULATION RATES :

If none is available, the mortality experience of the exposed groups is compared with the mortality experience of the general population in the same geographic area.

4.FOLLOW UP

Follow up is an important aspect of the cohort study.

The procedures required comprise :

1. Periodic medical examination of each member of the cohort.

2. Reviewing physician & hospital records.

Routine surveillance of death records.

Mailed questionnaires, telephone calls, periodic home visits – preferably all three on an annual basis.

5.ANALYSIS

The data are analyzed in terms of :

Incidence rates among outcome among exposed & non exposed.

Estimation of risk.

CONTINGENCY TABLE

Cases (with Ca lung )

Controls (without Ca lung )

Cigarette smoking

70 (a) 6930 (b)Yes

3(c) 2997(d)

No

Total

7000 (a+b)3000(c+d)

Incidence rates :

Among smokers = 70/7000 = 10 / 1000.

Among non smokers = 3/3000 = 3 / 1000.

Statistical Significance = P<0.001

ESTIMATION OF RISK : RELATIVE RISK : RR is the ratio of the

incidence of the disease or death among exposed & the incidence among non exposed.

RR = Incidence among exposed Incidence among non exposed.

RR = 10/1=10

(it is the measure of the strength of association between suspected cause & effect

ATTRIBUTABLE RISK

AR is the difference in incidence rates of disease between an exposed group & non exposed group.

AR = Incidence of disease rate among exposed minus incidence of disease rate among non exposed

Incidence rate among exposed

10 -1 10 Attributable risk indicates to what

extent the disease under study can be attributed to the exposure.

90% of the lung cancer among smokers was due to their smoking. This suggests the amount of disease that might be eliminated if the factor under study could be controlled or eliminated

* 100 = 90%

POPULATION ATTRIBUTABLE RISK

Population Attributable Risk is the incidence of the disease in the total population minus the incidence of disease among those who were not exposed to the suspected causal factor

Heavy smokers = 224 (a) exposed

Non smokers = 10 (b) non exposed

Deaths in total population = 74(c)

Individual RR = a/b =224/10 =22.40

Population AR =(c-b)/c = 86%

Deaths per 100,000 persons - years

ADVANTAGES OF COHORT STUDIES

Incidence can be calculated.Several possible outcomes related

to exposure can be studied simultaneously.

Provide a direct estimate of relative risk.

Dose Response ratio can be calculated.

Certain form of bias can be minimized as comparison groups are formed before disease develops

DIFFERENCES BETWEEN CASE CONTOL & COHORT STUDYNo

CASE CONTROL STUDY

COHORT STUDY

1 Proceeds from effect to cause

Proceeds from cause to effect

2 Starts with the disease

Starts with people exposed to risk factor or suspected cause

3 Tests whether the suspected cause occurs more frequently in those with the disease than among those without the disease

Tests whether disease occurs more frequently in those exposed, than in those not similarly exposed

4 First test to test the hypothesis

Reserved for testing of precisely formulated hypothesis

5 Involves fewer number of subjects

Involves larger number of subjects

6 Yields relatively quick results

Long follow up period

7 Suitable for study of rare diseases

Inappropriate when the disease under investigation is rare

8 Generally yields only estimate of RR

Yields incidence rates, RR as well as RR

9 Relatively inexpensive

Expensive

EXPERIMENTAL EPIDEMIOLOGY

Experimental studies are directly controlled & carried out under the investigator.

Experimental epidemiology is often equated with Randomized Control Trials.

Experimental studies involve some action, intervention or manipulation such as deliberate application or withdrawal of the suspected cause.

AIMS OF EXPERIMENTAL STUDIES

1. To provide scientific proof of aetiologic or risk factor.

2. To provide a method of measuring the effectiveness & efficiency of health services for the prevention, control & treatment of disease & improve the health of the community

AREAS OF EXPERIMENTAL STUDIES

1. Animal studies.2.Human experiments.

ANIMAL STUDIESAnimal studies have contributed to our knowledge of anatomy, physiology, pathology, microbiology, immunology, genetics, etc.

Classical animal experiments have given us a wide range of knowledge.

Important application of animal experiments are:

1.experimental reproduction of human disease in animals to confirm etiological hypothesis & to study the patho genetic phenomenon or mechanisms.

2.Testing the efficacy or preventive & therapeutic measures such as vaccines, drugs.

3.Completing the natural history of disease.

ADVANTAGES OF ANIMAL STUDIES

1.Experimental animals can be bred in laboratories & manipulated easily according to the wishes of the investigator.

2.They multiply rapidly & enable the investigators to carry put certain experiments (genetic experiments) which in human population would take several years..

LIMITATIONS

1. Not all human diseases can be reproduced in animals.

2.All conclusion drawn from animal experiments may not be strictly applicable to human beings. There are difficulties encountered in extrapolating findings from animal experiments in man

HUMAN EXPERIMENTS

1. Human experiments are always needed to investigate disease etiology & to evaluate the preventive & therapeutic measures.

2. Before launching human experiments, the benefits of the experiments have to be made aware of all possible consequences of the experiment.

Experimental studies are of two types :

1.RCT.2.Non RCT.

RCTThe design of a randomized controlled

trial is as follows.The basic steps in conducting a RCT

include the following:

1.Drawing up a protocol.2.Selecting reference & experimental

populations.3.Randomization.4.Manipulation or intervention.5.Follow up.6.Assessment of outcome.

DESIGN1. Select suitable population2. Select suitable sample3. Make necessary exclusions4. RANDOMIZE

Experimental group Control group

6.Manipulation & follow up

Not eligibleNo consent

1.THE PROTOCOLThe protocol :

1. Specifies the aims & objectives of the study.

2. Questions to be answered.

3. Criteria for the selection of the study & control groups.

4. Size of the sample.

5. The procedures for allocation of subjects into the study.

6. Treatments to be applied.

7.When & Where & how to what kinds of patients.

8.Standardization of work procedures.

Once the protocol has been evolved, it should be strictly adhered to throughout the study. Preliminary runs may be made to test the feasibility of the study.

2.SELECTING REFERENCE & EXPERIMENTAL POPULATIONS

REFERENCE OR TARGET POPULATIONS:

1. It is the population to which the findings of the trial, if found successful, are expected to be applicable.

2. A reference population may be as broad as a general population.

EXPERIMENTAL OR STUDY POPULATION :1.The study population is derived

from the reference population.

2.It is the actual population that participates in the study.

3.Ideally it should be randomly chosen from the reference population.

4. They must give an informed consent.

5. They should be representatives of the population to which they belong.

6. They should be qualified or eligible for the study.

7. Participants must be fully susceptible to the disease under study.

3.RANDOMIZATION

Randomization is a statistical procedure by which the participants are allocated into groups usually called “study” & “control” groups to receive or not to receive an experimental preventive or therapeutic procedure, manoeuvre or intervention.

1.Randomization is the “heart” of a control trial.

2.It will the greatest confidence that the groups are comparable so that “like can be compared with like”.

3.It ensures that the investigator has no control over the allocation of the participants to either study or control group

4.This eliminates selection bias.(Every individual gets an equal chance of being allocated into either group or any of the trial groups).

5. Randomization is best done by using a table of random numbers.

4.MANIPULATION

The experimental group is intervened or manipulated, by deliberate application or withdrawal or reduction of the suspected causal factor. (drug, vaccine, dietary component as laid down in the protocol).

The manipulation creates an independent variable whose effect is then determined by measurement of the final outcome, which constitutes the dependent variable (incidence of disease)

5.FOLLOW UP1.This implies examination of the

experimental & control group subjects art defined intervals

of time, in a standard manner.

2.The follow up may be short of for a long time.

3. There could be problems of attrition.

6.ASSESSMENT1.The final step is to assess the

result of the intervention.2.It may be a positive outcome or

a negative outcome.

3.The positive or negative result is rigorously compared both with the experimental & control groups.

BLINDINGBlinding can be done in three

ways.SINGLE BLIND : The trial is so

planed that the participant is not aware whether he belongs to the study or the control group.

DOUBLE BLIND TRIAL : The trial is so planned that neither the doctor nor the participant is aware of the group allocation & the treatment received.

TRIPLE BLIND : This goes one step further. The participant, the investigator & the person analyzing the data are all blind.

Ideally the triple blinding should be used.

But, most commonly the double blind is used.

EXPERIMENTAL STUDY DESIGNS1. Concurrent parallel study designs.

2. Cross over type of study designs.

Random assignment

Exposed to specific treatmentUn exposed to specific treatment

Compare OutcomePATIENT

S

Random assignment

PATIENTS

Exposed to specific treatmentUn exposed to specific treatment

TIME

Compare Outcome –Exposed & Un exposed

CONCURRENT PARALLEL STUDY DESIGN

Comparison are made between two randomly assigned groups, one group exposed to specific treatment, & the other group not exposed. Patients remain in the study group or the control group for the duration of the investigation

CROSS OVER STUDY DESIGN In this type of study each patient

serves as his own control

The patients are randomly assigned to the control & the study groups.

The study group receives treatment under consideration.

The control group receives a placebo.

Then patients are in each group are taken off their medication or placebo to allow for the possibility of any “carry over” effects.

After this period of medication the two groups are switched.

TYPES OF RANDOMIZED CONTOLLED TRIALS1.clinical trials.2.preventive trials.3.risk factor trials.4.cessation experiments.5.trial of etiological agents.6.evaluation of health services.

CLINICAL TRIALS

Clinical trials have been concerned with evaluation therapeutic agents, mainly drugs.

A clinical trial is a powerful tool that is carried out before any new therapy, procedure or service is introduced.

PREVENTIVE TRIALSPreventive trial implies trials of primary prevention measures.

These trials are purported to prevent or eliminate on an experimental basis.

The most frequently occurring trials of vaccines

The basic experimental designs are applicable for these trials.

Analysis of a preventive trial must result in a clear statement about:

1.The benefit that the community will derive from the measure.

2. The risks involved.3. The costs to the health

services in terms of man, money, material resources.

RISK FACTOR TRIALS

This is a preventive trial in which the investigator intervenes to interrupt the usual sequence in the development of disease for those individuals who have “risk factor”, for developing disease.

CESSATION EXPERIMENTS

In this type of study, an attempt is made to evaluate the termination of a habit, (or a removal of the suspected etiological factors),which is associated to the causal of disease.

If such action is followed by a significant in the reduction in the disease, the hypothesis if the cause is greatly strengthened.

TRIAL OF ETIOLOGICAL AGENTS

A trial of the etiological agents are under taken & followed up for the development of the effect or the disease.

E.g.,Retrolental fibroplasia as a cause of blindness among pre mature babies.

EVALUATIONOF HEALTH SERVICES.

RCT have been extended to assess the effectiveness & efficiency of health services.

Often choices have to be made between alternative policies of health care delivery services.

The necessity of choice results from the fact that resources are limited & priorities must be set for the implementation of a large number of activities which could contribute to the welfare of the society.

NON RANDOMIZED CONTROL TRIALS

1.Uncontrolled trials.2.Natural experiments.3.Before & after comparisons studies

USES OF EPIDEMIOLOGY

1.To study the natural history of disease in the population.

2.Community diagnosis.3.Planning & evaluation.4.Evaluation of individual’s risks &

chances.

5.Syndrome identification.6.Completing the natural history of

the disease.7.Searching for causes & risk factors.

1.STUDY THE DISEASE LOAD IN THE COMMUNITY1. Epidemiology aims at

closely studying the diseases load in the community

2. Epidemiology provides a means to study disease profiles & time trends in human population.

3.By a study of these trends, we can make useful projections into the future & identify emerging health problems & their correlates.

4.Epidemiology provides information about the disease fluctuations in the community.

2.COMMUNITY DIAGNOSIS

1.Epidemiology helps in diagnosing the health status of the community.

2.It quantifies the health related events in the community in terms of morbidity, mortality, natality , disability & other statistics related to the health events in the population.

3.By quantification of health problems, we lay down priorities in disease control & prevention.

4.Quantification of morbidity & mortality serves as a benchmark for the evaluation of health services. at a later date.

5.Quantification of health problems can be a source of new knowledge about disease distribution, causation & prevention.

6.Community diagnosis has been effectively extended beyond population distributions & profiles of illness to include an understanding of the social, cultural & environmental characteristics of the community.

7.Epidemiology therefore has been described as a “DIAGNOSTIC TOOL”

3.PLANNING & EVALUATION

1.Planning is essential for a rational allocation of the resources.

2.Epidemiologic information about the distribution of health problems over time & place provides the fundamental basis for planning & developing the needed health services.

3.Epidemiology helps in assessing the impact of the health services provided to address people’s problems.

4.The application of epidemiological principles to problems of health care constitutes the “new epidemiology”, E.g. planning facilities for medical care, man power planning.

5.Epidemiology helps in evaluating the health care services outcome.

6.The development of RCT has made it possible to evaluate treatment modalities on a firm scientific basis.

4.EVALUATION OF INDIVIDUAL’S RISKS & CHANCES1.One of the important tasks

of an epidemiologist is to make a statement about the degree of risk in a population.

2.Study of Relative Risk, Attributable Risk,Population Atributable risk, & other parameters related of the strength between cause & association offer us information on risk status of an individual & community.

5.SYNDROME IDENTIFICATION

1.Medical syndromes are identified by observing frequently associated findings in individual patients.

2.Epidemiological investigations can be used to define & redefine syndromes.

3.Epidemiological studies have been able to correct misconceptions concerning many disease syndrome.

6.COMPLETING NATURAL HISTORY OF DISEASEEpidemiology is concerned with

the entire spectrum of disease in a population.

2.The epidemiologist by studying the disease patterns in the community are in a better position to fill the gaps in the natural history of diseases.

3.Epidemiological investigations yield a large amount of data on risk factors in relation to chronic diseases.

7.SEARCHING FOR CAUSES & RISK FACTORS

1.Epidemiology by relating disease to inter population differences & other attributes of the population tries to identify the caused of the diseases.

2.The concept of “risk factors” give us renewed impetus to epidemiologic research.

EPIDEMIOLOGY