Fundamentals of Epidemiology,

Epidemiologic Methods, Design and

Conduct of Clinical Trials

Faraza Javed

Ph.D Pharmacology

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Introduction

The term epidemiology is derived from the Greek wordepidemic.

Epi means-Among, upon,

Demos means study population or people and

Logos means scientific study.

So

It is the scientific study of the disease pattern in humanpopulation.

In broad sense, it is the study of effects of multiple factorson human health.

It is multidisciplinary subject involving those of thephysician, Biologists, Public Health experts, Healtheducators etc.

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The science of the mass phenomena of infectious

diseases or the natural history of infectious diseases.

(Frost 1927)

The science of infective diseases, their prime causes,

propagation and prevention. (Stallbrass 1931)

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The widely accepted definition of epidemiology is:

“The study of the distribution and determinants of

health related states or events in specified

population and the application of the study to

control of health problems”

(J.M. Last 1988)

Aims of Epidemiology

According to the International Epidemiological Association(IEA) Epidemiology has three main aims.

To describe and analyze diseases occurrence anddistribution in human populations;

To identify etiological factors in the pathogenesis ofdiseases;

To provide the data essential to the planning,implementation and evaluation of services for theprevention, control and treatment of diseases and to thesetting up of priorities among those services.

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Components of Epidemiology

Disease frequency:

The core characteristics of epidemiology are tomeasure the frequency of diseases, disability or deathin a specified population. it is always as the rate, ratioand proportion.

Much of the subject of epidemiology are matter ofmeasurement of diseases and health related eventsfalls in the domain of biostatistics, which is a basictool of epidemiology. This helps in development ofstrategies for prevention or control of health relatedproblems.

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Distribution of Diseases:

Health events occur in pattern in community andthis pattern varies from community to community.

Also health events or diseases condition affectpopulation at various age groups, different genders,different subgroups of population.

Distributions of events are based on time, place, andperson. We can analyze whether any increases ordecreases occur for a particular condition.Epidemiology addresses itself to a study of thesevariations or patterns, which may suggest or lead tomeasure to control or prevent the diseases. Animportant outcome of this study is formulation ofetiological hypothesis.

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Determinants of Diseases:

Epidemiology helps in identifying the causative

agent or the risk/predisposing factors of diseases.

This is one of the real uses of epidemiology.

Understanding the factors leading to any programs

for the control of those diseases.

How to study the disease in the

community?

Clinical Method: Studied subject is a patient

(individual person) and decision on his/her

treatment requires a clinical diagnosis (based

on the history, examination, laboratory tests,

etc.).

Epidemiological Method: Epidemiology

studies not only an individual, but also a

whole population. Community diagnosis is

essential and can be expressed in terms

of rates.

Basic Measurement

Prevalence Rate

Incidence rate

Case fatality rate

Mortality rates(age specific/cause specific)

Attack rate

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Prevalence vs. Incidence

Prevalence: frequency of existing cases

Incidence: frequency of new cases

New cases are called incident cases.

Existing cases are called prevalent cases.

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PREVALENCE RATE

No. of people with disease at specified time/No. of

people in Population at risk at specified time

x 1000

Prevalence rate is often used to measure the occurrence of

chronic (long lasting) diseases or diseases with gradual

onset (such as diabetes, sclerosis multiplex, tuberculosis

etc.)

Ex: The Percentage of under five children

with acute malnutrition in Africa in March

2008

INCIDENCE RATE

Incidence Rate is defined as the no. of NEW cases occurring

in a defined population during a specified time period.

No. of new cases of specific disease during a given time

period/ Population at risk during that period

X 1000

Incidence rate is often used to measure the occurrence of

acute (short-term) diseases or diseases with exactly defined

onset (such as acute intestinal diseases, poisonings, car

accidents, strokes, etc.)

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For example , if there had been 500 new cases of

an illness in a population of 30,000 in a year, the

incidence rate would be :

500/30000 x 1000 = 16.7

Incidence rate refers to only new cases.

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ATTACK RATE

The attack rate, or case rate, refers to the

cumulative incidence of infection over a period

of time. This is typically used during an

epidemic. The time period may not be indicated,

but would typically refer to the period of the

outbreak.

Ex:

Outbreak of cholera in country X in March 1999

Number of cases = 490,

Population at risk = 18,600

Then the Attack rate = 2.6%

CASE FATALITY RATE

Measure of the severity of a disease which defined as the

proportion of cases of a specified disease or condition

which are fatal within a specified time

= no. of death from a disease in a specified period

no. of diagnosed cases of disease in same period

X 100

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The proportion of people with a specified condition who

die within a specified time. The time frame is typically

the period during which the patient is sick from the

disease. This works for an infectious disease but can be

problematic for a chronic disease like a cancer that may

remit for a period and then prove fatal after a

recurrence. In such instances we tend to speak of

mortality or survival rates rather than case fatality.

MORTALITY RATE

The number of deaths per thousand population per

year: in effect, the incidence of death in a

population. It can refer to all causes of death, or

can be a cause-specific mortality rate.

It expresses the no. of death due to a particular cause (or in

a specific age group) per 100 (or 1000) total deaths

No. of deaths from the specific disease in a year x 100

Total deaths from all causes in that year

EPIDEMIOLOGICAL STUDIES

When we need to obtain more precise or detailed data, it

may be necessary to undertake a special survey.

Planning of the study:

Definition of the aim of the study and type of the

study.

Determination of the studied population (target

population)-to exactly define the attributes of

individuals belonging to this population (including

and excluding criteria)

Case definition – to define a tool for discrimination

positive and negative cases. This tool (method)

should be cheap, simple and readily available.

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Epidemiologic Study Designs

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Study Design

Study design is the arrangement of conditions for the

collection and analysis of data to provide the most accurate

answer to a question in the most economical way.

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Types

1. Cross-sectional studies

2. Case-control studies

3. Cohort studies

4. Experimental studies

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Cross-sectional Studies

In this study design information about the status of an

individual with respect to presence/absence of exposure

and diseased is assessed at a point in time.

Cross-sectional studies are useful to generate a hypothesis

rather that to test it

For factors that remain unaltered overtime (e.g. gender,

race, blood group) it can produce a valid association

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Cross-Sectional…

Comparison groups are formed after data collection

The object of comparison are prevalence of exposure or

disease

Groups are compared either by exposure or disease status

Cross-sectional studies are also called prevalence studies

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Cross-sectional…

Types of cross-sectional studies

1. Single cross-sectional studies

Determine single proportion/mean in a single

population at a time

2. Comparative cross-sectional studies

Determine two proportions/means in two

populations at a time

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Cross-sectional…

Advantages of cross-sectional studies

Less time consuming

Less expensive

Provides more information

Describes well

Generates hypothesis

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Cross-sectional…

Limitations of cross-sectional studies

Antecedent-consequence uncertainty

“Chicken or egg dilemma”

Data dredging leading to inappropriate comparison

More vulnerable to bias

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Case-Control Studies

Subjects are selected with respect to the presence (cases)or absence (controls) of disease, and then inquiries aremade about past exposure

We compare diseased (cases) and non-diseased (controls)to find out the level of exposure

Exposure status is traced backward in time

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Case-control…

Steps in conducting case-control studies:

Define who is a case

Establish strict diagnostic criteria

All who fulfil the criteria will be “case population

Those who don’t fulfil will be “control population”

Individuals are divided according to presence of the

disease: studied group (disease present, e.g. lung

cancer) and control group (disease absent, e.g.

without lung cancer). Occurrence of suspected risk

factor in history is compared in both groups (e.g.

proportion of smokers) (studies focused from

consequence to cause)

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Case-control…

Advantages of case-control studies

Optimal for evaluation of rare diseases

Examines multiple factors of a single disease

Quick and inexpensive

Relatively simple to carry out

Guarantee the number of people with disease

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Cohort studies

Subjects are selected by exposure and followed to see

development of disease

Two types of cohort studies

1. Prospective (classical)

Outcome hasn’t occurred at the beginning of the

study

It is the commonest and more reliable

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Cohort…

2. Retrospective (Historical)

Both exposure and disease has occurred before the

beginning of the study

Faster and more economical

Data usually incomplete and in accurate

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Cohort…

Steps in conducting cohort studies

Define exposure

Select exposed group

Select non-exposed group

Follow and collect data on outcome

Compare outcome b/w exposed & non-exposed

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Cohort…

Advantages of cohort studies

Valuable when exposure is rare

Examines multiple effects of a single exposures

Allow direct measurement of risk

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Cohort…

Limitations of cohort studies

Expensive

Time-consuming

Loss to follow-up creates a problem

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Experimental studies

Individuals are allocated in to treatment and control

groups by the investigator. If properly done,

experimental studies can produce high quality data.

They are the gold standard study design.

They included studied group (intervention, e.g.

vaccinated children), control group (without

intervention, e.g. non-vaccinated children)

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Experimental…

The quality of “Gold standard” in experimental

studies can be achieved through

Randomization

Blinding

Placebo

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Experimental…

Randomization: random allocation of study subjects in to

treatment & control groups

Advantage: Avoids bias & confounding

Increases confidence on results

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Experimental…

Single blinding: Study subjects don’t know to which

group they belong

Double blinding: Physicians also don’t know to which

group study subjects belong

Triple blinding: Data collectors also don’t know

allocation status

Advantage: Avoids observation bias

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Experimental…

Placebo: An inert material indistinguishable from active

treatment

Placebo effect: Tendency to report favourable response

regardless of physiological efficacy

Placebo is used as blinding procedure

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Screening

Screening refers to the presumptive identification of a

disease/defect by application of tests, examinations or

other procedures in apparently healthy people.

Screening is an initial examination

Screening is not intended to be diagnostic

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Aims of screening program

Changing disease progression efficiently

Altering natural course of disease

Protecting society from contagious disease

Allocating resources rationally

Selection of healthy people for job

Studying the natural history of disease

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Criteria for establishing screening

program

The problem should have public health importance

There should be accepted treatment for positives

Diagnostic & treatment facilities should be available

Recognized latent stage in the time course

Test is acceptable, reliable & valid

Natural history of the disease should be well

understood

Case-finding is economical and continuous

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In general, a screening test should be

Reliable & valid

Sensitive & specific

Simple & acceptable

Effective & efficient

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Thank you!