Epidemiology

Historical Events of Epidemiology

If we trace back the origin of epidemiology in modern medicine, the following events have their
pioneer position:
Hippocrates have mentioned in his book on " air, water and places and also about seasons,
winds, rising sun, etc. somewhere about twenty five centuries back. Some physician said that
Hippocrates used the word ' consider ' not ' count ', but definitely Hippocrates have the pioneer
place, when today we talk about relationship between man and environment.
John Grant while working on the bills of mortality in London in 1662, made an attempt
to give numerical value to the events.
Not only science but the total development of human beings is due to their keen observation
in the natural events of their surroundings. It may be the observation of Newton about falling an
apple on earth or it may be an observation of John Snow about disease of cholera, who formulated
his hypothesis in the year 1849 before the invention of microscope or even knowledge about
microscope, that cholera is related with drinking contaminated water and signs and symptoms are
due to lesions in the intestine.
Mr. Lind tried fresh fruits in the treatment of scurvy in 1747.
Jenner's experiment in 1796 with cowpox vaccine is a landmark in the field of
immunization.
In 1905 Fletcher assessed the protective effect of curd rice against beri - beri in Kuala
Lumpur lunatic asylum, which was previously considered a contagious disease.
Goldberger inducted the pellegra by deficient diet in 1915.
Definition of Epidemiology
Epidemiology has been defined by Jhon M. Last in 1988 as-
“The study of the distribution and determinants of health-related status or events in specified
populations, and the application of this study to the control of health problems”.
Or
Epidemiology is the study and analysis of the distribution, patterns and determinants of health
and disease conditions in defined population. It is a cornerstone of public health, and shapes
policy decisions and evidence-based practice by identifying risk factors for disease and targets
for preventive healthcare.

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Modern Epidemiology

Modern epidemiology deals with, in addition to chronic diseases, the other health related states
that is not a medical condition but can give rise to health consequences. The concept has started
with the search for non - communicable diseases and its horizon towards genetic epidemiology,
pharmaco-epidemiology, immuno - epidemiology, social epidemiology etc.

Modern epidemiology has entered the most exciting phase of its evolution. By identifying risk
factors of the chronic diseases, evaluating treatment modalities and health services, it has provided
new opportunities for prevention, treatment, planning and improving effectiveness and efficiency
of health services.

Aims of Epidemiology
According to the International Epidemiological Association (IEA), epidemiology has three
main aims:
1. To describe the distribution and magnitude of health and disease problems in human
population.
2. To identify etiological factors (risk factors) in the pathogenesis of diseases and
3. Provide data essential to planning, implementation and evaluation of services for the
prevention, control and treatment of disease and to the setting up of priorities among
those services.

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 The ultimate aim of epidemiology is to lead to effective action:
1. To eliminate or reduce the health problem or its consequences; and
2. To promote the health and well-being of society as a whole.

Purpose of Epidemiology
1. To provide a basic for developing disease control and prevention measures for groups at
risk. This translates into developing measures to prevent or control disease.
2. To investigate nature / extent of health - related phenomena in the community / identify
priorities.
3. To study natural history and prognosis of health related problems.
4. To identify causes and risk factors.
5. To recommend / assist in application of / evaluate best interventions (preventive and
therapeutic measures).
6. To provide foundation for public policy.

Measurements of Epidemiology
1. Measurement of mortality.
2. Measurement of morbidity.
3. Measurement of disability.
4. Measurement of natality.
5. Measurement of presence or absence of attributes.
6. Measurement of health care need.
7. Measurement of environmental and other risk factors.
8. Measurement of demographic variables.

Objectives of Epidemiology
1. To identify the etiology, or cause, of a disease and its relevant risk factors (i.e., factors that
increase a person’s risk for a disease).
2. To intervene to reduce morbidity and mortality from the disease
3. To develop a rational basis for prevention programs based on identified etiologic or causal
factors
4. To work on to reduce or eliminate exposure to those factors
5. To develop appropriate vaccines and treatments, which can prevent the transmission of the
disease to others.
6. To determine the extent of disease found in the community.
7. To help plan health services and facilities for effective health care facilities
8. To study the natural history and prognosis of the disease.

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 9. To define the baseline natural history of a disease in quantitative terms so that as we
develop new modes of intervention, either through treatments or through new ways of
preventing complications
10. To help compare the results of using new modalities with the baseline data to determine
whether new approaches have truly been effective.
11. To evaluate both existing and newly developed preventive and therapeutic measures and
modes of health care delivery
12. To help provide the foundation for developing public policy relating to environmental
problems, genetic issues, and other social and behavioral considerations regarding disease
prevention and health promotion.

Scope of Epidemiology
Epidemiology, as defined by ' Last ', concerns not only disease and death components but also
other health related events. In this way, it also gives indication to improve upon the situation after
knowing the distribution and determinants of disease or events. So in this way, epidemiology is a
basic medical science with the goal of improving the health of populations.
The scope of epidemiology can be:
1. Causation of disease: The knowledge of distribution of disease in terms of time, place and,
person provides hypothesis and this is further tested and confirmed by various epidemiological
studies. These causative factors may be genetic or environmental or it may be causation of both
which leads to ill health.
2. Natural history of disease: Epidemiology is a very important and significant tool to study the
natural history of any disease. Epidemiologists study the disease pattern in the community in
relation to agent, host and environmental factors. One can study a complete pattern of disease
starting from good health, subclinical disease, clinical disease, disability and recovery from
disease or even death.
3. Classification of disease: The epidemiological observations suggest that various diseases are
having different determinants and should be classified accordingly, e.g. peptic ulcer group should
not include gastric and duodenal ulcer as one, as they are different in etiology. Similarly vehicle
and vector borne diseases are classified according to their key determinant. These provide an
insight for further management.
4. Description of health status of population: Epidemiology is often used to describe the health
status of population groups. Knowledge of the disease burden in population is essential for health
managers who guide us, in relation to limited resources for the best possible effect.

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5. Evaluation of intervention: These days epidemiologist are involved in evaluating the
effectiveness and efficiency of health services by determining the appropriate length of stay in
hospital or community interventions for specific conditions under national health programmes.
 Treatment regimen for blood pressure in diabetes
 Efficiency of sanitation measures to control diarrheal diseases.
 Input of vitamin A supplement, iron and folic acid tablets.
 Utilization of health services, i.e. knowing about OPD attendance.
6. Planning: The planning of any community or country is the hallmark of development. Similar
is the case with health planning.
 Epidemiology provides indices, which is important to know the load of problems. In its
first step, it provides a list of problems.
 Planning starts when the magnitude of problem is in hand. Then these problems are
prioritized, keeping in view the resources of the country.

Uses of epidemiology
1. Establishing the dimensions of morbidity and mortality as a function of person , place
and time
2. Quantifying risks of developing morbidity
3. Identifying and defining syndromes
4. Describing the full clinical spectrum of disease and illness
5. Describing the natural history of disease
6. Identifying factors which influence or predict clinical course
7. Identifying causes of disease , disability and mortality
8. Evaluating methods of disease prevention and control

Function of epidemiology
Core epidemiologic functions: in the mid- 1980s, five major tasks of epidemiology in public
health practice were identified-
1. Public health surveillance
2. Field investigation
3. Research
4. Evaluation and
5. Policy development.

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The success/Achievements in epidemiology

The health of the public has markedly improved in the twentieth century, through direct and
indirect benefits from health-related research. The top public health accomplishments of the 21st
century as published in the CDC’s Morbidity and Mortality Weekly Report are:

1. Vaccine-preventable diseases
2. Prevention and control of infectious diseases
3. Tobacco control
4. Maternal and infant health
5. Motor vehicle safety
6. Cardiovascular disease prevention
7. Occupational safety
8. Cancer prevention
9. Childhood lead poisoning prevention
10. Improved public health preparedness and response.

Types of epidemiological studies

1. Observational studies
a. Descriptive studies
b. Analytical studies
i) Ecological
ii) Cross - sectional
iii) Case control
iv) Cohort
1. Experimental studies Intervention studies
a. Randomized controlled trial
b. Field trials
c. Community trials

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 Descriptive study
A descriptive study is concerned with conditions or relationships that exist, opinion that are help,
processes that are going on, effect that are evident, or trends that are developing. It is primarily
concerned with present, although it often considers past events and influences as they relate to
current conditions. They are limited to the description of a disease only and no comparison is
made with the reference population.

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 and identifying the characteristics with which the disease in question
seems to be associated. Such studies basically ask the questions.

a. When is the disease occurring? - Time distribution

b. Where is it occurring? - Place distribution
c. Who is getting the disease? - Person distribution

Descriptive studies: These are presented in terms of-

 Disease in community
 Community in disease

Disease in Community

It means who are affected, which areas are affected and at what time it shows maximum effect.
They basically answer three questions who, when and where or we can say they center around
time, place and person.

Community in Disease

It means health status of community, i.e. which are the major diseases in the community? Which
is the disease of significant severity in terms of disability? Which section of the community are
the worst effected?

This type of interpretations about health and disease of community is also known as '
community diagnosis '.

Person, Place and Time Variation

Descriptive studies primarily aim at describing the disease or health related events by time, place
and person. This is done by collection of data or by already collected data.
One must remember that this is just sorting of data or grouping of variables according to time,
place and person characteristics and this must not be interpreted as any One must remember that
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this is just sorting of data or grouping of variables according association of causal factors. It can
also be understood as the first clue towards the causal relationship which initiates for further
queries or further designing of the more detailed studies. The purpose of categorizing the disease
must be kept in mind, i.e. the categorization should be purposeful, so that the inference leads to
some scientific designing of next step, i.e. analytic study and fruitful intervention.
Person Variation
Person can be described in terms of either their inherent or acquired characteristics such as age,
sex, race, religion, occupation, marital status, socio - economic status, etc.
These characteristics determine to a large extent that which persons are at greatest risk of acquiring
a specific disease.
1. Age: It is the most important variable which must be considered in epidemiological studies.
For most diseases the variation in frequency that occurs normally due to increasing age are
greater than those to be found in association with any other variables . Each infectious
disease has its own characteristics age incidence, e.g. measles and whooping cough have
their highest incidence between the age group of 1-5 years, while diphtheria and mumps
are more common in school going children.
Association of disease frequency is measured by relating the number of cases in each
group to the population in the same group and deriving age specific incidence or prevalence
rates.
Age grouping should be kept relatively small to detect differences. Large groups are
likely to hide the age specific incidence in the distribution of cases.
Age is related with maturity of organ system, efficiency of defense mechanisms and
rate of health decline.
Age indicates the cumulative outcome of a lifelong agent - host interaction. This must
be kept in mind that environmental factor is not same in all individual and so is the agent -
host interaction.
Sometimes there may be two separate peaks instead of one in the curve of diseases as
in the case of Hodgkin's disease, leukemia and female breast cancer. It holds special value
which indicates that either the data collected is not homogenous or the two different causal
factors are operating in the two modes.
2. Sex: The study of sexwise distribution of cases and deaths due to a particular disease is a
time tested epidemiological practice. Some diseases for obvious anatomical reasons are sex
specific. In others an excess of incidence in one sex depends upon more subtle differences
in the constitute make up of sexes. But the circumstantial differences are also indicative of
the difference in disease incidence.

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Disease like thyrotoxicosis, cholecystitis, diabetes, obesity, arthritis and psychoneurosis are more
frequent in women while diseases like peptic ulcer, lung cancer, coronary heart disease and
various kinds of accidents are more common in men.
Cultural and behavioral factors also influence the health and disease. Of course the group of
diseases related to reproductive health of women especially of pregnancy and childbirth are
exclusive to females
3. Race / groups / ethnicity / religion / nativity: The basic point in this is the sharing of same
living environment for a long time. They not only share some biological characteristics but also
social mechanisms. The grouping of disease according to these groups is more, so it is a stimulus
for further studies, that whether the diseases are related to genetic constitution or environmental
factors.
4. Occupation: The general condition under which a person works (apart from exposure to
specific physical and chemical agents) may play an important part in determining his disease
experience. For example workers working in the coal mines likely to suffer from silicosis,
similarly diabetes and hypertension are more among people, which are working as an executive
or have office jobs.
Occupation also influences the pattern of habits of employees, e.g. sleep, night shifts,
tobacco and alcohol consumption and their eating patterns. It is now well evident that workers of
call centers are showing new set of diseases. Occupation of a person is also used as an index of
his socio - economic status and it has its own impact on health and disease.
5. Marital Status: When mortality rates among married and unmarried are studied, they show
that mortality is less among married. As the married persons feel secure and have a sense of
responsibility towards family so they live more. Unmarried people are tense; feel socially
unacceptable, so indulge in unhealthy health practices. On the other hand cancer cervix is more
among married women. It is almost absent in nuns.
6. Socio - economic Status: Socio - economic status is reflection of occupation, education and
income of an individual. It, of course, affects the health and disease due to purchasing power of
individual, his / her social status in the community and life style due to education and occupation.
There is definite and significant difference between various socio - economic groups or different
social classes as far as the disease pattern is concerned. It is certain that nutrition, housing,
sanitation, stress are various other determinants which are entirely different in all these groups.
7. Lifestyle: In present day scenario, a new group of diseases is coming up which has been given
the name of lifestyle diseases. It is linked with behavior of human beings. The factors which have
proved to be linked with this group of diseases are cigarette smoking, sedentary life style, altered
dietary habits, i.e. more inclination towards fast food, ready to eat food, feel good foods and stress
.

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 Place Variation
Place Distribution (Geographical comparisons)
Studies of the geography of disease (or geographical pathology) is one of the important
dimensions of descriptive epidemiology. By studying the distribution of disease in different
populations we gain perspective on the fascinating differences (or variations) in disease patterns
not only between countries, but also within countries. The relative importance of genes versus
environment; changes with migration; and the possible roles of diet and other aetiological factors.
In short geographical studies have profoundly influenced our understanding of disease, its nature,
its detriments and its relation to subsequent pathology. The geographic variation in disease
occurrence has been one of the stimulants to national and international studies.
Geographic patterns provide an important source of clues about the causes of the disease. The
range of geographic studies include those concerned with local variations. At a broader level,
international comparisons may examine mortality and morbidity in relation to socio - economic.
factors, dietary differences and the differences in culture and behavior. These variations may be
classified as-
1. International variations
2. National variations
3. Rural-urban variations
4. Local distributions
International variations
Descriptive studies by place have shown that the pattern of disease is not the same everywhere.
For example, we know that cancer exists all over the world. There is, however, a marked
difference between the incidences of each cancer in different parts of the world. Thus cancer of
the stomach is very common in Japan, but unusual in US. Similarly, there are marked international
differences in the occurrence of cardiovascular diseases. These variations have stimulated
epidemiologists to search for cause - effect relationships between the environmental factors and
disease. The aim is to identify factors which are crucial in the cause and prevention of disease.
National variations
It is obvious that variations in disease occurrence must also exist within countries or national
boundaries. For example the distribution of endemic goitre, lathyrism, fluorosis, leprosy, malaria,
nutritional deficiency diseases have all shown variations in their distribution in India, with some
parts of the country more affected and others less affected or not affected at all. Such situations
exist in every country. One of the functions of descriptive epidemiology is to provide data
regarding the type of disease problems and their magnitude in terms of incidence, prevalence and
mortality rates. Such information is needed to demarcate the affected areas and for providing
appropriate health care services.
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Rural - urban variations
Rural / urban variations in disease distribution are well known. Chronic bronchitis, accidents, lung
cancer, cardio vascular diseases, mental illness and drug dependence are usually more frequent in
urban than in rural areas. On the other hand, skin and zoonotic diseases and soil - transmitted
helminths may be more frequent in rural areas than in urban areas. Death rates, especially infant
and maternal mortality rates, are higher for rural than urban areas. These variations may be due to
differences in population density, social class, deficiencies in medical care, levels of sanitation,
education and environmental factors.
Local distributions
Inner and outer city variations in disease frequency are well known. These variations are best
studied with the aid of 'spot map ' or 'shaded maps’. These maps show at a glance areas of high or
low frequency, the boundaries and patterns of disease distribution. For example if the map shows
"clustering" of cases , it may suggest a common source of infection or a common risk factor shared
by all the cases.
Importance
 These results stimulate to search for cause - effect relationships between the environmental
factors and disease so that preventive can be initiated.
 They also provide the region wise magnitude of the problem within the country. .
 Urban - rural differences can reflect the deficiency in medical care, levels of education,
sanitation, environmental factors, and social class. This can provide a ' high risk group ' for
the administrators to work with.
 It is also evident that with the knowledge of agent, host and environment interaction, the
scenario of disease in terms of distribution of disease pattern has dramatically changed.

Time Variation
Time is another important aspect, which gives clue in the epidemiological investigation.
We can understand the concept of time according to the length of time necessary for the
changes to develop in progression of disease.
It can be studied in following types-
 Diurnal variation
 Seasonal variation
 Cyclic or periodic variation
 Secular or long term variation

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1. Diurnal Variation
They are the variations shown by a disease within a day, e.g. blood pressure or glaucoma.

2. Seasonal Variation
It is the tendency to high or low incidence shown by many diseases at certain times of the year
such as diarrhea in summer season and measles or ARI in winter season. Other vector borne
diseases like malaria, dengue, filarial, etc. May and June are known as malaria months.
Allergic diseases like hay fever and asthma also show seasonal trends. These are related to
the environmental factors, which changes with climate like breeding and feeding habits of
disease vectors, housing seasons, indoor and outdoor living pattern of the population.

3. Cyclic Variation
Some diseases show a tendency of periodic recurrence after a fixed period. This trend is
related with the herd immunity of a particular area, which decreases to certain level after a
fixed period and makes the population prone / vulnerable for that disease.

4. Secular Variation
These changes refer to changes that occur gradually over long periods of time and usually
imply changes in disease frequency measured over a period of several years or decades. This
trend can be upward or downward as we see in case of diabetes, CVD, obesity, cancers that
there is increase in number of cases in last three - four decades. We can also observe that
polio, typhoid, tuberculosis and other communicable diseases that are towards decline. This
change in either direction can be due to awareness among people and implementation of
national health programmes.
Importance
Analysis of cases by time enables the formulation of hypothesis concerning the time and source
of infection, mode of transmission and causative agent as well as incubation period. Cases of a
particular disease recorded according to date, month, year, etc. also provide definite knowledge
about the period of incubation as well as the likely future trend. All these are necessary for
planning appropriate preventive and control measures.

Epidemic Trends
Definition: The "unusual" occurrence in a community or region of disease, specific health -
related behaviour (e.g., smoking) or other health - related events (e.g. traffic accidents) clearly in
excess of "expected occurrence".
The term "outbreak" is used for a small, usually localised epidemic in the interest of minimizing
public alarm, unless the number of cases is indeed very large.

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Types of Epidemic
There are three major types of epidemics –
1. Common - source epidemic.
 Single exposure or "point source" epidemics.
 Continuous or multiple exposure epidemics.
2. Propagated Epidemic
 Person to person
 Arthropod vector
 Animal reservoir
3. Slow (modern) epidemics.
Epidemic Curve
A graph of the time distribution of epidemic cases is called the "epidemic curve".
The epidemic curve may suggest:
i. A time relationship with exposure to a suspected source.
ii. A cyclical or seasonal pattern suggestive of a particular infection, and com source
propagated spread of the disease.
Common - source, single exposure epidemics Exposure
These 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. Time The exposure to the disease agent is brief and essentially simultaneous, the
resultant cases all develop within one incubation period of the causative agent, e.g., an epidemic
of food poisoning.
Main features of Common - source, single exposure epidemic and its curve:
i. The epidemic curve rises and falls rapidly, with no secondary waves.
ii. The epidemic tends to be explosive, there is clustering of cases within a narrow interval
of time.
iii. All the cases develop within one incubation period of disease.
Propagated epidemics
 These are most often of infectious origin and result from person to person transmission of
an infectious agent, e.g., epidemics of hepatitis A and polio.
 The speed of spread of propagated epidemics depends upon herd immunity, opportunities
for contact and secondary attack rate.

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  Propagated epidemics are more likely to occur where large number of susceptibles are
aggregated, or where there is a regular supply of new susceptible individuals (e.g., birth
or immigrants) lowering herd immunity.
Or, Propagated Epidemic
 It is from person to person.
 Gradual rise in cases
 Sustained plateau.
 Gradual fall
 More likely to occur where large number of susceptible cases are gathered or new
susceptible cases arrive regularly
 For example , viral hepatitis , poliomyelitis

Cross – sectional studies

Cross - sectional studies can be categorised as:
 Snap Shot
 Portrait of Community
 Measurement of Exposure
 Effect of Exposure
Cross - sectional studies measure the prevalence of disease and are often called prevalence
studies. They are carried out at a single point of time. So they present the snapshot or a portrait
of community.
In cross - sectional studies the measurement of exposure and effect are made at the same
time, so they are relatively easy.
Design of Cross - sectional Study
Following steps are taken:
1. Defining study population
2. Defining the disease or event
3. Observation and analysis
4. Bias and limitations
5. Advantages and disadvantages
Limitation
It is not easy to assess the reasons for association demonstrated in the study.

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The data collected is not much useful for comparison of two situations as there is lack of
standardized techniques of interviews. The design of questionnaire and sample should be planned
and appropriate to have better comparisons.
Uses / Advantages
 These are relatively easy and economical to conduct.
 Useful for investigating the exposure which is the fixed characteristics of individuals as
socioeconomic status, blood groups etc.
 It is the most convenient first step for investigating the cause during sudden outbreak.
 Data collected in these studies is helpful in assessing the healthcare needs of population.

Case control study

Case control studies, often called "retrospective studies are a common first approach to test causal
hypothesis. In recent years, the case control approach has emerged as a permanent method of
epidemiological investigation. The case control method has three distinct features:
i. Both exposure and outcome (disease) have occurred before the start of the study
ii. The study proceeds backwards from effect to cause; and
iii. It uses a control or comparison group to support or refute an inference.

By definition, a case control study involves two populations - cases and controls. In case control
studies, the unit is the individual rather than the group. The focus is on a disease or some other
health problem that has already developed.
Case control studies are basically comparison studies. Cases and controls must be comparable
with respect to known "confounding factors" such as age , sex , occupation , social status , etc.
Basic steps
There are four basic steps in conducting a case control study:

1. Selection of cases and controls

2. Matching
3. Measurement of exposure, and
4. Analysis and interpretation.

1. Selection of cases and controls

The first step is to identify a suitable group of cases and a group of controls. While identification
of cases is relatively easy, selection of suitable controls may present difficulties. In this
connection, definite guidelines have been laid down such as the following.
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(1) Selection of Cases
(a) Definition of a case: The prior definition of what constitutes a "case" is crucial to the case
control study. It involves two specifications: (i) Diagnostic Criteria: The diagnostic criteria of the
disease and the stage of disease, if any (e.g. breast cancer Stage I) to be included in the study must
be specified before the study is undertaken. Supposing we are investigating cases of cancer, we
should be quite clear that we have, for our cases, a group histologically the same. Once the
diagnostic criteria are established, they should not be altered or changed till the study is over. (ii)
Eligibility Criteria: The second criterion is that of eligibility. A criterion customarily employed is
the requirement that only newly diagnosed (incident) cases within a specified period of time are
eligible than old cases or cases in advanced stages of the disease (prevalent cases).
(b) Sources of cases: The cases may be drawn from (i) hospitals, or (ii) general population. (i)
Hospitals: It is often convenient to select cases from hospitals. The cases may be drawn from a
single hospital or a network of hospitals, admitted during a specified period of time. The entire
case series or a random sample of it is selected for study. (ii) General Population: In a population
- based case control study, all cases of the study disease occurring .within a defined geographic
area during a specified period: of time are ascertained, often through a survey, a disease registry
or hospital network . The entire case series or a random sample of it is selected for study. The
cases should be fairly representative of all cases in the community.
(2) Selection of Controls
The controls must be free from the disease under study. They must be as similar to the cases as
possible, except for the absence of the disease under study. As a rule, a comparison group is
identified before a study is done, comprising of persons who have not been exposed to the disease
or some other factor whose influence is being studied. Difficulties may arise in the selection of
controls if the disease under investigation occurs in subclinical forms whose diagnosis is difficult.
Selection of an appropriate control group is therefore an important prerequisite, for it is against
this, we make comparisons, draw inferences and make judgements about the outcome of the
investigation.
Sources of controls: The possible sources from which controls may be selected include hospitals,
relatives, neighbors and general population. (1) Hospital Controls: The controls may be selected
from the same hospital as the cases, but with different illneses other than the study disease. For
example, if we are going to study cancer cervix patients, the control group may comprise patients
with cancer breast, cancer of the digestive tract, or patients with non - cancerous lesions and other
patients. (ii) Relatives: The controls may also be taken up from relatives (spouses and siblings).
Sibling controls are unsuitable where genetic conditions are under study. (iii) Neighbourhood
Controls: The controls may be drawn from persons living in the same locality as cases, persons
working in the same factory or children attending the same school. (iv) General Population:
Population controls can be obtained from defined geographic areas, by taking a random sample

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of individuals free of the study disease. We must use great care in the selection of controls to be
certain that they accurately reflect the population that is free of the disease of interest.
2. Matching
The controls may differ from the cases in a number of factors such as age, sex, occupation, social
status, etc. An important consideration is to ensure comparability between cases and controls. This
involves what is known as "matching". Matching is defined as the process by which we select
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 disease and which, if not
adequately matched for comparability, could distort or confound the results.

There are several kinds of matching procedures. One is group matching. This may be done by
assigning cases to sub - categories (strata) based on their characteristics (e.g., age, occupation,
social class) and then establishing appropriate controls. The frequency distribution of the matched
variable must be similar in study and comparison groups. Matching is also done by pairs. For
example, for each case, a control is chosen which can be matched quite closely. Thus, if we have
a 50 year old mason with a particular disease we will search for 50 year old mason. without the
disease as a control. Thus one can obtain pairs of patients and controls of the same sex, age,
duration and severity of illness etc.
3. Measurement of exposure
Definitions and criteria about exposure (or variables which may be of aetiological importance)
are just as important as those used to define cases and controls. Information about exposure should
be obtained in precisely the same manner both for cases and controls. This may be obtained by
interviews, by questionnaires or by studying past records of cases such as hospital records,
employment. records etc.

4. Analysis
The final step is analysis, to find out-

(a) Exposure rates among cases and controls to suspected factor

(b) Estimation of disease risk associated with exposure (Odds ratio)
(a) Exposure Rates
With this data we calculate exposure rate as:
Exposure rate among
i. Case = a / (a + c) x100

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ii. Control = b / (b + d) × 100
In CVD patients, type A personality and disease, the following is the data in a particular study .
Exposure rate among
i. Cases: 33/35 x 100 = 94.2 %
ii. Control: 55/82 x 100 = 66 %
So, we can observe that CVD is more among patients with type A personality as compared to
other types of personality.
Table: Distribution of cases and control in relation to type of personality
Case Control
Type A personality 33 55
Other 02 27
Total 35 82

RISK RATE: (Strength Of Association)

This is calculated as:
Risk rate = incidence among exposed / incidence among non - exposed
Table: Distribution of cases and control in relation to total serum cholesterol
Level Total serum Disease present Disease absent
cholesterol
0 < 220 132 211
1 220-260 138 81
2 > 260 24 02

As we know that in case control study , incidence cannot be calculated , because there is no
proper denominator or we can say , exact number of population at risk is not known so in this
case , to know the strength of association , we calculate odd's ratio .
ODD'S RATIO ( OR )
It is ratio of exposure among cases and control
OR = chance of exposure among cases / chance of exposure among control
( factor present and disease present ) x ( factor absent and disease absent )
ODDS ratio =
( factor present and disease absent ) x ( factor absent and disease present )
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 axd
OR =
bxc

It is also known as cross - product ratio. As it is not real, it is also known as 'pseudo relative risk’
In the study of CVD cases the following data was obtained.
CVD patient and level of total serum cholesterol
Comparing (calculating zero level and one level)
OR = 138 x 211/132 x 81 = 27
Calculating zero level and two level
OR = 211 x 24 / 132 x 2 19.18
So , it is evident that if the total serum cholesterol level is increased to 1st level as compared to
normal ( zero level ) the risk increase 2.7 fold and if it increases to 2nd level ( > 260 ) , the risk
increases 19.18 times .
There are so many tests available in biostatistics and according to the acquired data these
are applied.
Here in this case ' chi - square test ' is applied to ascertain whether the relation between
total serum cholesterol and CVD is significant or not. For this, P value ' is calculated, which tells
us whether the probability of association between the disease and suspected factor has occurred
by chance or by real fact. If the P - value is 0.05 or less than that, the relation is considered
significant. The lesser the P - value higher is the significance.
Bias And Limitations
There are following bias observed in case - control study
a. Selection bias
b. Memory bias / recall bias
c. Interviewer bias
d. Confounding bias
e. Berkesonian bias
f. Unacceptability bias

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a. Selection Bias
It is bound to occur in case control studies as the cause - effect phenomenon has already occurred.
If response rates are different, even then selection bias can occour. It can be reduced by the method
that cases and controls should be drawn from different population, but after proper matching.
Multiple controls should be drawn from variety of sources.
b. Memory / recall Bias
There are two reasons for this bias:
Cases and control have different types of reporting due to their exposure, which has
resulted in illness in one and none in other.
There may be faulty memories of an individual.
c. Interviewer Bias
In this case, the interviewer knows who the case is and who the control is. So the approach towards
the case is different and towards control it can be casual. A more detailed history is sorted from
cases while controls are not devoted so much time. This can be reduced by preparing the series of
queries and questions and asking all relevant questions to either group or the interviewer should
not be disclosed about the status of cases and control.
d. Confounding Bias
It has already been discussed that how confounding produces the bias. Confounding means a
factor which provides misleading estimates of effect.
It can be removed by proper matching.
e. Berkesonian Bias
It is a special type of bias observed by Dr. Berkesonian. It is a selection bias as the control and
cases are taken from hospital and there is different rate of admission to hospital for different people
with different diseases.
f. Unacceptability Bias
People may not give correct information about their personnel, sensitive issues like sexual
practices, drugs, etc. This can be reduced by formulating a questionnaire which is of indirect
nature.
Advantages of case control studies
1. Relatively easy to carry out.
2. Rapid and inexpensive (compared with cohort studies).
3. Require comparatively few subjects.

20 | P a g e (Prepared by Sharmin Akter Sumi, Lecturer, NHS, JUST)

 4. Particularly suitable to investigate rare diseases or diseases about which little is known.
But a disease which is rare in the general population (e.g. leukaemia in adolescents) may
not be rare in special exposure group (e.g. prenatal X - rays).
5. No risk to subjects.
6. Lesser subjects (people) are required.
7. No issues with of diagnostic criteria, administrative setup, as follow up is not required.
8. Allows the study of several different aetiological factors (e.g. smoking, physical activity
and personality characteristics in myocardial infarction).
9. Risk factors can be identified. Rational prevention and control programmes can be
established.
10. No attrition problems, because case control studies do not require follow - up of
individuals into the future.
11. Ethical problems minimal.
Disadvantages of case control studies
1. Problems of bias relies on memory or past records, the accuracy of which may be
uncertain; validation of information obtained is difficult or sometimes impossible.
2. Selection of an appropriate control group may be difficult.
3. Incidence rate cannot be measured, and can only estimate the relative risk.
4. Attributable risk cannot be calculated , so prophylaxis evaluation is not possible
5. Do not distinguish between causes and associated factors.
6. Not suited for evaluation of therapy or prophylaxis of disease.
7. Another major concern is the representativeness of cases and controls.
8. Recall bias is a main problem.
Cohort study
Cohort study is known by a variety of names as follows:
 Prospective study
 Longitudinal study
 Incidence study
 Forward - looking study.
Cohort study is a type of analytical (observational) study which is usually undertaken to obtain
additional evidence to refute or support the existence of an association between suspected cause
and disease.
Distinguishing Features of Cohort studies-
1. The cohorts are identified prior to the appearance of the disease under investigation.

21 | P a g e (Prepared by Sharmin Akter Sumi, Lecturer, NHS, JUST)

 2. The study groups ("study cohort" and "control cohort") are observed over a period of time
to determine the frequency of disease among them.
3. The study proceeds forward from "cause to effect ".
4. Cohort studies are done to test a precisely formulated hypothesis.
What is Cohort?
The term "cohort" is defined as a group of people who share a common characteristic or
experience (e.g. age, occupation, exposure to a drug or vaccine, pregnancy, insured persons etc.)
within a defined time period. For example, persons exposed to a common drug, vaccine or
infection within a defined period form an "exposure cohort".
Indications of cohort studies
1. To measure the incidence of disease.
2. To find out the cause of disease.
3. If there is good evidence of an association between clinical observations and supported by
descriptive and case control studies.
4. If exposure is rare, but the incidence of disease is high among the exposed persons. For
example, special exposure groups in certain industries, or exposure to X - rays, etc.
5. If attrition of study population can be minimised, e.g. follow - up is casy, cohort is stable,
co - operative and easily accessible.
6. If adequate funds are available.
Types of cohort Studies
There are three types of cohort studies on the basis of the time of occurrence of disease in relation
to the time of investigation is initiated and continued:
1. Prospective cohort studies.
2. Retrospective cohort studies
3. A combination of retrospective and prospective cohort studies
Prospective cohort studies ("Current" cohort study)
 This is one in which the outcome (e.g., disease) has not yet occurred at the time the
investigation begins.
 Most prospective cohort studies begin in the present and continue into future to investigate
the outcome (e.g., disease) in exposed and non - exposed cohorts.
Retrospective cohort studies ("Historical" cohort study)
 This is one in which the outcome (e.g., disease) has occurred before the start of the
investigation.

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  The retrospective cohort studies go back in time sometimes 10 to 30 years. The study
groups are selected from existing records of past medical or other records which are traced
forward through time from a past date fixed on the records, usually up to the present.
 This type of study is also known as prospective study in retrospect and non - concurrent
prospective study.
Combined retrospective and prospective cohort studies
 This is one in which both the retrospective and prospective elements are combined.
 The cohort is identified from past records, and is assessed of date for the outcome. The
same cohort is followed up progressively into future for further assessment of outcome.
 A cohort study begins with a group of people who are free of disease, and who ae classified
into subgroups (e.g., exposed and non exposed) according to exposure to a potential cause
of disease or outcome.
 Variables of interest are specified and measured and the whole cohort is followed up to see
how the subsequent development of new cases of disease (or other outcome) differs
between the groups with and without exposure.

Figure: Design of a cohort study.

Elements of cohort study-
(i) Selection of study subjects
(ii) Obtaining of data on exposure
(iii) Selection of comparison groups
(iv) Follow up
(v) Analysis

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 Selection of study subjects
The subjects of a cohort study are usually selected is one of two ways - tither from general
population or special groups of the population.
a) General population: Cohort may be selected from the general population of a defined
geographical area, when the exposure or case of death is fairly frequent in the population.
If the population is very large, an appropriate sample is taken from both the exposed and
unexposed segments of the population.
b) Special groups: These may be-
 Select groups- may be professional groups (e.g., doctors, nurses, lawyers etc.), insured
persons, obstetric population, government employees etc. These groups are usually a
homogeneous population.
 Exposure groups- may be selected due to special exposure to physical, chemical and other
disease agents. For example, workers in industries and those employed in high risk
sanitations (eg., radiologists exposed to X - rays).
Obtaining Data on Exposure
Data may be obtained directly from the following sources:
a) Cohort members: Through personal interviews or mailed questionnaires. The mailed
questionnaires offer a simple and economic way to obtain data
b) Review of records: e.g. medical records, hospital records etc.
c) Medical examination or special tests
d) Environmental surveys.
Information about exposure (or any other factor related to the development of the disease being
investigated) should be collected in a manner that will allow classification of cohort members as
follows:
i. according to exposed or not - exposed to the suspected factor, and
ii. according to the level or degree of exposure in the case of special exposure groups.
Selection of Comparison Groups
The ways of selecting comparison groups are –
i. Internal comparisons: Single cohort enters the study, and its members are classified into
several comparison groups according to the degrees or levels of exposure to risk (e.g.
smoking, blood pressure, serum cholesterol) before the development of the disease in
question. The groups so defined, are compared in terms of their subsequent morbidity and
mortality rates.

24 | P a g e (Prepared by Sharmin Akter Sumi, Lecturer, NHS, JUST)

 ii. External comparisons: Outside comparison group is necessary to evaluate the experience
of the exposed group when information on degree of exposure is not available. For
example, smokers and non - smokers.
iii. Comparison with general population rates: When nothing is available, the mortality
experience of the exposed group is compared with the mortality experience of the general
population in the same geographic area as the exposed people. For example comparison of
frequency of lung cancer among uranium mine workers with lung cancer mortality in the
general population where the miners resided.
Rates for disease occurrence in sub - groups of the control cohort by age, sex, and other
variables may be applied to the corresponding sub - groups of the study cohort (exposed
control) to determine the values in the absence of exposure.
The ratio of "observed" and "expected" values provides a measure of the effect of the factor
under study.
Follow - up
Methods of regular follow - up include:
 Periodic medical examination of each member of the cohort.
 Reviewing records of hospital and physician.
 Routine surveillance of death records.
 Mailed questionnaires, telephone calls, periodic home visits- preferably on an annual
basis.
Analysis
The data are analyzed in terms of:
i. Incidence rates of outcome among exposed and unexposed. In a cohort study, incidence
rates can be determined directly in those exposed and those not exposed.
ii. Estimation of risk in terms of two well - known indicates, e.g., (a) relative risk, and (b)
attributable risk.
Relative Risk (RR) / Risk Ratio
It is the ratio of the incidence of the disease (or death) among exposed and the incidence among
non - exposed.
Incidence of disease (or death) among exposed
RR =
Incidence of disease (or death) among non - exposed

25 | P a g e (Prepared by Sharmin Akter Sumi, Lecturer, NHS, JUST)

 A relative risk ( RR ) of 1 indicates no association, a RR greater than I suggests "positive"
association between exposure and the disease under study; RR = > 2 indicates that the incidence
rate of disease is 2 times higher in the exposed group as compared to the unexposed.
Attributable Risk (AR) / Risk Difference
It is the difference in incidence rates of disease (or death) between an exposed group and non -
exposed group, which is expressed as a percent.

Incidence of disease rate among exposed –

Incidence of disease rate among non - exposed
AR = X 100
Incidence rate among exposed

AR indicates to what extent the disease under study can be attributed to the exposure.
Population - Attributable Risk ( PAR )
It is the incidence of the disease (or death) in the total population minus the incidence of disease
(or death) among those who were not exposed to the suspected casual factor, which is expressed
as percent.
Incidence of disease (or death) in total population –
Incidence of disease (or death) in non - exposed.
PAR = X 100
Incidence of disease (or death) in total population

Differences between Relative risk and Attributable risk

Features Relative risk ( RR ) Attributable risk ( AR )
Definition The ratio of the incidence of the disease The difference in incidence rate of
(or death) among exposed and among non disease (or death) between an exposed
- exposed. group and non - exposed group.
Expression It is expressed in number times of It is expressed as a percent.
occurrence.
Measure / Index / It is direct measure or index of the It indicates to what extent the disease
Indicator “strength” of the association between the under study can be attributed to the
suspected cause and effect. exposure.
Suggestion It suggests the etiological role of causal It suggests the amount of disease that
factor in occurrence of disease might be eliminated if the factor under
(or death). study could be controlled or eliminated.

26 | P a g e (Prepared by Sharmin Akter Sumi, Lecturer, NHS, JUST)

Public health It is used in assessing the likelihood that It is used to reduce the risk of disease
an association represents a causal by elimination or control of a particular
relationship effect relationship. exposure So, if gives an idea about the
impact of successful preventive or
public health programme in reduction
of health problem.

Differences between Case control and Cohort studies (between Retrospective and
Prospective study)
Case control Study ( Retrospective study ) Cohort study ( Prospective study )
1. Proceeds from 'effect to cause'. 1. Proceeds from ' cause to effect.
2. Starts with the disease. 2. Starts with people exposed to risk factor or
suspected cause.
3. Tests whether the suspected cause occurs more 3. Tests whether disease occurs more frequently in
frequently in those with disease than among those those exposed than in those not similarly exposed.
without the disease.
4. Usually the first approach to the testing of a 4. Reserve for testing of precisely formulated
hypothesis. hypothesis.
5. Involves fewer number of subjects. 5. Involves larger number of subjects.
6. Yields relatively quick results. 6. Long follow up period often needed, involving
delayed results.
7. Suitable for the study of rare disease. 7. Inappropriate when the disease is rare.
8. Only estimates relative risk (RR). 8. Yields incidence rates, RR as well as attributable
risk.
9. Can't yield information about more diseases 9. Can yield information about more than one
other than that selected for study. disease outcome.
10. Relatively inexpensive. 10. Expensive.

Advantages and Disadvantages of Cohort study

Advantages
1. The incidence of the disease can be calculated.
2. Direct calculation of risk ratio (relative risk).
3. Dose - response ratio can also be calculated.
4. Particularly important for investigation of rare cause.
5. Several possible outcomes related to exposure can be studied simultaneously. For example,
cohort studies designed to study the association between smoking and lung cancer also
showed association of smoking with coronary heart disease, peptic ulcer, cancer
oesophagus etc.
6. Certain forms of bias can be minimized.
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 7. Strongest observational design to establish cause and effect relationship.
Disadvantages
1. Not suitable to study uncommon diseases or diseases with low incidence in the population.
2. Takes a long time to complete the study and obtain results (20-30 years or more in cancer
studies).
3. Often requires a large sample size. It is difficult to keep a large number of individuals under
medical surveillance for indefinite period.
4. A substantial proportion of the original cohort may be lost due to migration, lost of interest
in the study or refusal to participate in the study.
5. Selection of comparison groups which are representative of the exposed and unexposed
segments of the population is a limiting factor.
6. Expensive to do cohort studies.
7. The study itself may alter behaviour of the study population, which may influence in the
outcomes of the study.
8. With any cohort study there are ethical problems of varying importance.
9. In a cohort study, practical considerations dictate that must be concentrated on a limited
number or factors possibly related to disease outcome.

EXPERIMENTAL EPIDEMIOLOGY
Experimental epidemiology is also known as intervention epidemiology.
Experimental or interventional studies are carried out in such conditions that are under the direct
control of the investigator. Experimental or interventional studies involve experiment in two
groups: experimental group and control group. There are some actions, interventions or
manipulations in these studies, which are strictly determined by laid down protocol or plan.
Aims of experimental studies
i. To provide scientific proof of aetiological (or risk) factors which may permit the
modification or control of those diseases; and
ii. To provide a method of measuring the effectiveness and efficiency of health services for
the prevention, control and treatment of disease and improve the health of the community.
Types of experimental studies
i. Randomized controlled trials (i.e. those involving a process or random allocation ); and
ii. Non - randomized or "non - experimental" trails (i.e. those departing from strict
randomization for practical purposes, but in such a manner that non - randomization does
not seriously affect the theoretical basis of conclusions).

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 Randomized Controlled Trials
A randomized controlled trial is experiment designed to study the effects of a particular an
epidemiological intervention.
To ensure equivalent comparison of the groups, subjects (patients) are allocated to them randomly,
i.e , by chance into groups , usually called treatment and control groups . The results are assessed
by comparing the outcome in the two or more groups. If the initial selection and randomization of
the groups is done properly, this ensures that control and treatment group will be comparable at
the start of an investigation.
Steps of RCT
1. Drawing up a protocol
2. Selection of study population
3. Selection of suitable participants by defined criteria as per plan.
4. Randomization of participants
5. Treatment group or study group and control group
6. Intervention or manipulation
7. Follow - up
8. Assessment of outcome, (disease / no disease)

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Field Trials
This involves healthy populations who are free from disease but are at risk. For example: infants
and young children who are at risk of developing measles in the community.
Trial of vaccine is an example of field trial. It is conducted on healthy children or healthy
population in the field. According to protocol the study population is defined and participants are
chosen and assigned to experimental and control groups and intervention is done. One group is
immunized and other is non - immunized. These two groups are followed for a defined period
(say one year or longer) and the outcome or incidence of disease occurrence in both groups is
recorded and the results are compared in two groups.
Disadvantage of field trials
Field trials causes huge undertaking involving major logistics and financial considerations.

Community trials
In these studies, the treatment groups are communities rather than individuals.
The best example of community trials is supply of iodized salt to community and reduction of
prevalence of the problem of goiter in the community.

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