PHARMACY PRACTICE-II

COMMUNITY PHARMACY
EPIDEMIOLOGY & ITS CONTROL

DR.RABIA GUL
 EPIDEMIOLOGY
Epidemiology is the study of “WHERE AND WHEN”
diseases occur & “HOW” they are transmitted within
population
OR
Epidemiology is the study and analysis of the
distribution and determinants of health related events
or states in specified population.
Application of epidemiological studies is to control
health related problems
 Disease
frequency
Disease frequency

Distribution

Incidence Prevalence
Determinants

Number of new cases of the Total number of cases (both new

disease in a given area or and already existing cases) in a
population during a given period given area or population during
of time given period of time
Distribution
Distribution of frequencies and patterns of health events

Determinants causes or factors that are associated with increased

risk or probability of disease
Epidemiological studies
• Research to study the dynamics of diseases in population
• Basic science of public health and based on principles of
statistics and research methodologies.

PURPOSE OF EPIDEMIOLOGICAL STUDIES

• To identify causes of diseases in a given population
• Developing measures to prevent or control disease
transmission
Issues epidemiology can address
• Disease
• Mortality
• Morbidity
• Hospitalization
• Disability
• Natality
• Quality of Life
• Health Status
IMPORTANT DEFINITIONS
• Endemic: Occurs routinely in a given area or population
• Disease that normally occurs continually (at moderately regular
intervals) at relatively stable incidence within a given population or
geographical area is said to be endemic to that area
• E.g. AIDS endemic in Africa
• Malaria, Hepatitis, Polio, Tuberculosis are endemic in Pakistan
• Epidemic: Whenever a disease occurs at a greater frequency than
usual for an area or population the distribution is said to be epidemic
• Epidemic is outbreak of a disease or an unexpected event
• E.g. Dengue fever in Pakistan (2011)
• SARS in China (2002)
• Hemolytic uremic syndrome by E.coli in 2011 in Germany
• Ebola in West Africa (2013–2016)
• Pandemic: A pandemic is an epidemic of infectious disease that has
spread across a large region; for instance multiple continents, or even
worldwide
• Pandemic is the worldwide spread of a new disease.
E.g.
• AIDS
• Tuberculosis
• SARS
• Malaria
• Leprosy
• Swine Flu in 2009
• Sporadic: When only a few scattered cases occurs within an area or
given population
• E.g. meningitis
• Alzheimer
• Crimean-Congo hemorrhagic fever (sporadic cases in rural areas of
Pakistan)
Descriptive studies
• Descriptive epidemiology, it is concerned with observing the distribution
of disease in human population and identifying the characteristics with
which the disease seems to be associated
• Careful tabulation of data concerning a disease
• Relevant information includes the Location and time of cases of the
disease as well as information about the patient such as age, gender,
occupation, health histories, socioeconomic groups etc.
• Because time course and chain of transmission of a disease are important
part so there is need to identify INDEX CASE (first case) in a given
population
• E.g. in 1854 John Snow studied Cholera outbreak in London
• By mapping the locations of cholera cases he found cases cluster around
broad street water pump
• So he concluded cholera spreads by contamination of drinking water
Procedure in descriptive studies
1. Defining the population to be studied
• whole population or a representative sample
• Define population in terms of characteristics i.e. age, gender,
occupation, socioeconomic status etc.
2. Defining the disease under study
3. Describing the disease by
OCCURANCE
• Time
AND
• Place DISTRIBUTION
• Person
4. Measurement of disease
5. Comparing with known indices
6. Formulation of etiological hypothesis
1. Defining the population to be studied
• Descriptive studies are investigations of population.
• A defined population should not only be in terms of total number but
also in terms of age, gender, occupation, etc.
• The defined population
a) could be a whole geographic region or a representative sample
b) could be a specially selected group- based on age, gender,
occupation, etc.
c) should be large enough so that it is meaningful
d) should be stable without migration into or out
e) should not be different from other communities in the region.
2. Defining the disease under study
• The epidemiologist defines the disease which can be measured and
identified in the defined population with a degree of accuracy.
• This is different from the clinician’s definition of a disease
 3. Describing the disease
Time Place Person
• Year, • Climatic zones • Age • Birth order
• Season • Country, • Gender • Family size
• Month, • Region • Marital • Height
• Week • Urban/Rural state • Weight
• Day, • Local • Occupation • Blood pressure,
• Hour of onset community • Social • Blood
• Duration • Towns status, cholesterol,
• Cities • Education • Personal habits
• Institutions
A: Short term fluctuations
• An epidemic is the best known short term fluctuation. It is defined as “ The
occurrence in a community or region of cases of an illness or other health
related events clearly in excess of normal expectancy
Types:
• 1) Common source epidemics
i) Single/Point exposure
ii)Continuous/Multiple exposure
2) Propagated epidemics
i) person to person
ii)arthropod vector
iii)animal reservoir
3) Slow(modern) epidemics
Common source epidemics
1) Single exposure:
It can occur due to an infectious agent or as a result of contamination
of the environment and develops within one incubation period. Eg:
Bhopal gas tragedy,
The epidemic curve rises and falls rapidly, usually has one peak
• It tends to be explosive (i.e. clustering of cases within a short time)
2. Continuous/Multiple exposure
• It is when the exposure from the same source is prolonged and the
epidemic continues over more than one incubation period.
• The epidemic reaches a sharp peak, but tails off gradually over a
longer period of time.
• Eg: A well of contaminated water or food; water borne cholera.
• nationally distributed vaccine (polio vaccine)
Propagated epidemics
• Types- person to person, arthropod, animal
• The epidemic shows gradual rise and tails off over a much longer
period of time
• It is more likely to occur where there is
i) regular supply of new susceptible individuals- Births, Immigrants
ii) lowering herd immunity
B) PERIODIC FLUCTUATIONS
1) Seasonal trend-
Seasonal variation is characteristic of many communicable diseases. Eg:
Measles, upper respiratory tract infections(seasonal rise during winter),
Malaria, etc.
Non-infectious diseases and conditions may sometimes exhibit
seasonal variation.
Eg: Sunstroke, hay fever.
2. Cyclic trends
• Some diseases occur in cycles spread over short periods of time
(days, weeks, months or years) .
Eg: Influenza pandemics are known to occur at intervals of 7-10 yrs due
to antigenic variations.
• Non-infectious conditions may also occur in this trend. Eg:
Automobile accidents in the US are more frequent on weekends
C) LONG TERM TRENDS
• It refers to changes in the occurrence of disease over a long period of
time.
Eg: Coronary disease, diabetes showing consistent upward trend and a
decline in TB, polio in developed countries during the past 50 yrs.
INTERNATIONAL VARIATION
• Descriptive studies have shown that the pattern of a disease is not
the same everywhere
• Eg: Cancer of the stomach is very common in Japan, but unusual in
the US.
NATIONAL VARIATION
• There are variations in disease occurrence within countries.
• Eg: The distribution of endemic goiter, malaria, nutritional
deficiencies show variations in their distribution in Pakistan.
RURAL-URBAN VARIATIONS
• Due to differences in population density, levels of sanitation,
deficiencies of medical care, education and environment factors,
there exists a rural-urban variation
• Chronic bronchitis, cardiovascular diseases, accidents are more
frequent in urban than rural areas.
• Skin and zoonotic diseases and soil transmitted helminths may be
more frequent in rural than urban areas.
LOCAL DISTRIBUTIONS
• These variations can be studied with the help of “spot or shaded”
maps. If the map showed clustering, it may suggest a common source
of infection.
• Eg: Study of Cholera epidemic by John Snow in 1854
MIGRATION STUDIES
• The use of migrant studies is a way of distinguishing genetic and
environmental factors.
• Carried out in 2 ways-
1) Study of genetically similar groups but living under different
environmental conditions. Eg: Twins
2) Study of genetically different groups living in a similar environment.
Eg: Men of Japanese origin living in USA have higher rate of coronary
heart disease than the Japanese in Japan
PERSON DISTRIBUTION
• The disease can be characterized by defining a person who develops a
disease based on age, gender, occupation, marital status, social
factors, habits and other host factors.
• A) AGE
• Certain diseases are more frequent in certain age groups than others.
Eg: Measles in childhood, cancer in middle age and atherosclerosis in
old age.
• Many chronic and degenerative diseases show a progressive increase
in prevalence with advancing age.
• BIMODALITY
• There may be two separate peaks
instead of one in the age incidence
curve of a disease. This is known as
bimodality as seen in Hodgkin’s
lymphoma, breast cancer.
• It indicates that there are two
different sets of causative factors
even though the clinical and
pathological manifestations of the
disease is the same in all ages.
• B) gender
• Variations occur due to-
• 1) Biologic difference like sex linked genetic inheritance
• 2) Cultural and behavioral differences between the gender groups in
social settings.
• Eg: 4:1 male to female ratio in lung cancer due to cigarette smoking.
• ETHNICITY
• Differences in racial and ethnic origin.
• Eg: Tuberculosis, sickle cell anemia
• OCCUPATION
Occupation may alter the habit pattern of a employees (Sleep, alcohol,
smoking, etc)
• Workers in a particular occupation are exposed to certain types of
risk. Eg: Workers in coal mines are likely to suffer from silicosis
SOCIAL CLASS
• Health and diseases are NOT equally distributed in social classes.
• Certain diseases show higher prevalence in upper class (Diabetes,
Coronary heart disease, hypertension)
• BEHAVIOUR
• Behavioral factors such as smoking, sedentary life, over-eating, drug
abuse lead to certain diseases (Coronary heart disease, Cancer, etc)
• Factors like mass movement (Eg: Pilgrimages) may also lead to
transmission of infectious diseases.
• STRESS
• The effects of stress are seen based on the patient’s response
(Susceptibility to disease, Exacerbation of symptoms, etc)
STEP 4: MEASUREMENT OF DISEASE
• Types-
1) Cross sectional studies-
• Prevalence can be obtained.
• it is based on a single examination of a cross section of population at
one point in time.
• More useful for chronic diseases
• Longitudinal studies-
• Incidence can be obtained.
• The observations are repeated in the same population over a
prolonged period of time by means of follow up examination.
• Longitudinal is more useful, but it is time consuming.
STEP 5: COMPARING WITH KNOWN
INDICES
• Comparisons are made with known indices to arrive at clues to the
disease’s etiology
STEP 6: FORMULATION OF A
HYPOTHESIS
• A hypothesis is a supposition, arrived at from observation or
reflection
• An epidemiologic hypothesis should specify-
• The population- characteristics of the people to whom the hypothesis
applies
• Specific cause
• Expected outcome-the disease
• Dose response relationship-The amount of the cause needed to lead
to the stated incidence of the effect.
• Time response relationship-Time period between exposure to the
cause and observation of the effect.
USES OF DESCRIPTIVE EPIDEMIOLOGY
• It provides data regarding the magnitude of the disease load and
types of disease problems in terms of morbidity and mortality rates
and ratios.
• It provides clue to disease etiology and help in the formulation of an
etiological hypothesis.
• It provides background data for planning, organizing and evaluating
preventive service.
• Contribute to research by describing variations in disease occurrence
by time, place aand person.
ANALYTICAL EPIDEMIOLOGY
• Second major type of epidemiology.
• Focus on individual within population unlike descriptive
epidemiology..
• Objective not to formulate hypothesis but to test hypothesis
CASE CONTROL STUDY
• Retrospective study
Distinct features:
1. Both exposure and outcome have occurred before the start of
disease
2. Study proceed backward from effect to cause
3. Uses a control or comparison group to support or refute an
inference.
STEPS
1. Selection of cases and controls
2. Matching
3. Measurement of exposure , and
4. Analysis and interpretation.
SELECTION OF CASES AND CONTROL
A. Selection of case B. Selection of control

Definition of a case:
I). diagnostic criteria:
ii). Eligibility criteria
Sources of controls:
i)Hospital
controls(common
source of selection bias)
ii) Relatives
iii) General population

Sources of cases:
Number of
i) Hospital
controls/c ontrol groups
ii) General population
MATCHING
 Define as ”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 confounded the result”.
 CONFOUNDING FACTOR
 MEASUREMENT OF EXPOSURE
 Definition and criteria about exposure are just as
important as those used to define cases and controls.
 This may be obtained by :
 Interviews
 Questionnaires
 Studying past record of cases such as hospital records,
employment records etc.
 Clinical or laboratory examination.

Investigator should not know whether a

subject is in case or control group.
ANALYSIS AND INTERPRETATION
• The final step is analysis, to find out:
a) Exposure rates among cases and controls to suspected
factors

b) Estimation of disease risk associated with exposure

(ODD RATIO)
EXPOSURE RATE
Example of case control study of tobacco chewing and oral cancer

Cases Controls
(with oral cancer) (without oral cancer)
Tobacco
chewers 33 (a) 55(b)

Non-chewers 2 (c) 27(d)

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

EXPOSURE RATES
a. Cases =a/(a+c) = 3 3 / 3 5 = 94.2%
b. Controls = b / ( b + d ) = 5 5 / 8 2 = 67.0%
62
 CASE CONTROL STUDY

ADVANTAGES: DISADVANTAGES:
1. Relatively easy to carry out. 1. Problem of bias since it
2. Rapid and inexpensive relies on past memory or
3. Require fewer subjects. past records.
4. Suitable for investigation of 2. Difficulty in selection of
rare diseases. appropriate control group.
5. No risk of subject. 3. Can not measure
6. Allows the study of several incidence only RR.
different etiological factors. 4. Doesn’t distinguish
7. Risk factor can be identify between cause and
8. No attrition problem associated factors.
because do not require 5. Not suited for the
follow up. evaluation of therapy or
9. Minimal ethical problem. prophylaxis of disease.
Cohort study
Cohort study
 Prospective ,longitudinal, incidence and forward-
looking study

 Distinguishing features:
a) The cohorts are identified prior to the appearance
of the disease
b) The study groups, so defined, are observed over a
period of time to determine the frequency of disease
among them
c) Study proceeds from cause to effect.
Indication of cohort study
 When there is good association between exposure and
disease.
 When exposure is rare, but the incidence of disease is high
among exposed.
 When attrition of study population can be minimized.
Prospective cohort study
• Outcome has not yet occurred the time of investigation
begins.

Exposed Outcome

Measure exposure
and confounder
variables

Non-exposed Outcome
Baseline
time
Study begins here
Retrospective cohort study
• Outcomes have all occurred before the start of the investigation.

Exposed Outcome

Measure exposure
and confounder
variables

Non-exposed Outcome
Baseline
time
Study begins here
Element of a cohort study
1. Selecting of study subject
2. Obtaining data on exposure
3. Selection of comparison group
4. Follow up
5. analysis
 2.Obtaining data on
1. Selecting of study exposure
subject
Information about exposure may
When exposure or cause of be obtained directly f r om : -
death is fairly frequent in the
population

i. Select group –
Professional group (
doctors,nurses )

ii. Exposure group-High risk

situation (eg.radiologist
exposed to x-ray)

7
 4. Follow up
3 Selection of comparison
group  Main problem
a. Internal comparisons:-  Procedures to obtain data
for assessing the outcome
 Comparison groups are in built are:
(eg. Smoking, bp etc.) within
same cohort group. a. Periodic medical checkup
b. Reviewing hospital records
b. External comparisons:- c. Routine surveillance of
 Eg. Smoker and non smoker, death records
radiologists with d. Mailed questionnaries,
opthalmologists. telephone calls, periodic
home visits.
c. With General population:-
 If none is available, mortality of
exposed group with general
population
Analysis
Incidence rates of outcome among exposed and non-exposed:

RISK FACTOR DEVELOPED DID NOT TOTAL

(TOBACCO) ORAL CANCER DEVELOP

PRESENT 45 (a) 9955 (c) 10000 (a + c)

(CHEWERS)
ABSENT 5 (b) 9995 (d) 10000 (b + d)
(NON CHEWERS)

Incidence rates:
1. Among tobacco chewers: = 45/10000 = 4 .5 per 1000
2.Among non chewers = 5 /1 0 0 0 0 = 0.5 per 1000
b. Estimation of risk
A. Relative risk (RR):

= incidence of disease among exposed

incidence of disease among non-exposed

= 4.5/0.5
= 9

 It implies 9 times higher risk of development

of oral carcinoma in tobacco chewers
compared to non chewers.
B. Attributable risk (AR) Or “risk difference”:

Incidence of disease rate among exposed -incidence among non exposed

Incidence rate among exposed
= 4.5 – 0.5
4.5
= 88.9%

 Indicates to what extent the disease under study can be attributed

to the exposure.

7
 Advantages of cohort study
1. Incidence can be calculated
2. Several possible outcomes related to exposure can
be studied simultaneously.
3. Provide a direct estimate of RR.
4. Dose response ratios can be calculated.
5. Since comparison groups are formed before disease
develops, certain forms of bias can be minimized like
misclassification of individual.
 disadvantages of cohort study
1. Unsuitable for investigating uncommon disease.
2. Long time to complete study and obtain results.
3. Administrative problem –
 Extensive record keeping

4.Expensive
5. Alter people behavior
 Stop or decrease smoking

 Loss of interest

 migration

5. Ethical problem of varying important

1 Start disease :effect Start people: cause
cause effect.

2 First approach to test Reserved for testing precisely

hypothesis. formulated hypothesis.
3
Involve fewer subject. Involve larger number of
subjects.
4 Yield result quickly. Results are delayed due to
long follow up.
5 Suitable for studying rare Unsuitable for studying for
disease. rare diseases.

6 Gives RR only. Yield RR and AR.

7 Relatively inexpensive. Expensive
Does not give information Can give information more
8
about diseases other than that than one disease.
selected for the disease. 33
a
EXPERIMENTAL
EPIDEMIOLOGY
• Experimental or intervention studies are similar in approach to
cohort studies excepting that the conditions in which the study is
carried out are under the direct control of the investigator.
• It involves some action, intervention or manipulation such as
deliberate application or withdrawal of a suspected cause or
changing one variable in the causative chain in the experiment
group while making no change in the control group and observing
and comparing the outcome of the experiment in both the group.
Experimental epidemiology;
• Aim of experimental studies:
• To provide scientific proof of etiological factors which may permit the
modification or control of those disease.
• 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
Randomized Control Trial
• Randomisation is the process of assigning a trial participant randomly
(by chance) to treatment or control groups.
• Different tools are used to randomise (closed envelopes, computer
sequences, random numbers).
• There are two components to randomisation:
a) the generation of a random sequence
b) Implementation of the random sequence, ideally in a way so that
participants are not aware of the sequence.
Randomized Control Trail
Randomized Control Trail (RCT):
• In 1747, James Lind performed a human experiment (clinical trail) in
which he added different substances to diet of 12 soldiers who were
suffering from Scurvy.
• He divided his patient in to 6 pairs and supplemented the diets of
each pairs with cider, elixir vitriol (aromatic Sulphuric acid), vinegar,
sea water, a mixture of nutmeg, garlic, mustard and tamarind
(dates) in barley water and two oranges and one lemon.
• All the subjects were studied for 6 days, at the end of 6 days the
LIMEYS recovered from Scurvy and found fit for duty.
Randomized control trail;
The basic steps in conducting a RCT includes the following;
1) Drawing up a protocol.
2) Selecting reference and experimental populations.
3) Randomization.
4) Manipulation or intervention.
5) Follow up.
6) Assessment of outcome.
1) Drawing up a protocol;
One of the essential features of RCT is that the study is conducted
under a strict protocol. The protocol aims at preventing bias and to
reduce the source of error in the study.
It specifies the aims and objectives of the study, questions to be
answered, criteria for the selection of study and control group,
sample size, the procedure for the allocation of subjects into the
study and control group, treatment to be applied etc.
2) Selecting reference & experimental
populations;
Ideally it should be randomly chosen from the reference population
so that it has the same characteristics as the reference population. If
it differs it may not be possible to generalized the findings of the
study to the reference population. The participants must fulfill the
following criteria:
a) They must give informed consent
b) They should be the representative of the population to which they
belong.
c) They should be qualified or eligible for the study.
3) Randomization;
It is a statistical procedure by which the participants are allocated
into groups usually called study and control group to receive or not to
receive an experimental intervention.
It ensures that the investigator has no control over allocation of
participants to either study or control group thus eliminating
“selection bias”. By random allocation, every individual gets an equal
chance of being allocated into either group.
Randomization is done only after the participant has entered the
study, that is after having being qualified and has given informed
consent
4) Manipulation or intervention;

Having formed the study and control groups, the next step is to
intervene or manipulate the study group by the deliberate application
or withdrawal or reduction of the suspected causal factor. (e.g this
may be a drug, vaccine dietary component, a habit etc.) as laid down
in protocol.
This manipulation creates an independent variable e.g. drug, vaccine
whose effect is then determined by measurement of the final
outcome, which constitutes the dependent variable e.g. incidence of
disease, survival time, recovery time.
5) Follow-up;

This implies examination of the experimental and control group

subjects at defined interval of time, in a standard manner, with equal
intensity, under the same given circumstances, in the same time
frame till final assessment of outcome. The duration of the trail is
usually based on the expectation that a significant difference
(mortality) will be demonstrable at a given point in time after the
start of the trail.
Some losses to follow up are inevitable due to factors such as death,
migration and loss of interest. This is known as attrition.
6) Assessment of outcome;
The final step is assessment of the outcome of the trail in terms of
Positive health; that is benefits of the experimental measure such as
reduced incidence or severity of the disease, cost to the health
services or other appropriate outcome in the study and control group.
Negative results; that is, severity and frequency of side effects and
complication, if any, including death.
The incidence of positive/negative results is rigorously compared in
both groups, and the differences, if any, are tested for statistical
significances.
Bias;
Any systematic error that results in an incorrect estimation of the association b/w an
exposure and the outcome is called bias.
This may be from three sources;
Subject variations; There may be bias on the part of the participants, who may report
improvement if they knew they receiving a new form of treatment.
Observer bias; The investigator measuring the outcome of the trail may be influenced if
he knows beforehand the particular procedure.
Evaluation bias; The investigator may subconsciously may give a favorable report of the
outcome of the trail.
In order to reduce these problems, a technique known as Blinding is adopted.
 Blinding;
Blinding can be done in three ways;
1) Single blind trail; The trail is so planned
that the participant is not aware whether
he belongs to the study or control group.
2) Double blind trail; The trail is so planned
that neither the researcher nor the
participant is aware of the group
allocation & the treatment received.
3) Triple blind trail; This goes one step
further. The participant , the investigator
and the person analyzing the data are all
blind.
ideally the triple blind should be used but
the double blinding is the most frequently
used method when a blind trail is conducted.
Non-randomised controlled trials
• In a non-randomised study, participants are allocated into control or
treatment arms by a method that is not random. The investigator
defines and manages the alternatives.

• It is appropriate to use a non-randomised controlled trial design when

randomisation may be unethical, not suitable due to legal or political
challenges or when it is impractical in terms of cost and convenience.

• There are many possible types of non-randomised controlled trials

that do not use appropriate randomisation strategies (sometimes
called quasi-randomised studies).
Non-randomised controlled trials
Non-randomised controlled trials have the potential to study two
groups that are not strictly comparable. However, there are different
types of controls that can be used in non-randomised trials:
• Concurrent controls: the treatment and control group participants
are matched based on demographic and other characteristics. They
receive different treatments at the same time.
• Historical controls: the investigators compare outcomes among a
group of participants who are receiving a new treatment
(experimental group) with outcomes among participants who
received standard treatment in a previous period (control group).
APPLICATIONS OF EPIDEMIOLOGY
The epidemiology is useful in:
1. Search of risk factors/causes of diseases in community.
2. Helps to describe the health status of population or
groups.
3. Helps to discover and bridge gaps in natural history of
diseases.
4. Helps in controlling/Preventing the diseases. To break the
weakest link in chain of transmission of communicable
diseases and reducing non communicable diseases.
To study the cause (or etiology) of disease(s), or
conditions, disorders, disabilities, etc.
To determine the primary agent responsible or causative factors
To determine the characteristics of the agent or causative factors
To define the mode of transmission
To determine contributing factors
To identify and determine geographic patterns
To determine, describe, and report on the natural course of disease,
disability, injury, and death
5. Helps in planning of health programs on evidence basis and
setting up of health priorities. It provide administrative and planning
data
6. Helps to evaluate health programs and interventions
7. Helps to determine the chances or probability of occurrence
of disease/ deaths and disability
8. Helps in better management of health services and hospital
services.
9. Helps to set-up cut-off levels between normal and abnormal
population and establish trigger levels for action or
intervention.
10. Syndrome identification in specified group or population
Pharmacoepidemiology
Pharmacoepidemiology is the study of the use and effects of
drugs in large numbers of people
This provides a bridge between clinical pharmacology and
epidemiology.
The increasing demand for real-world evidence of the
safety, efficacy and utility of medicinal products has focused
greater attention on pharmacoepidemiological research.
 Pharmacoepidemiological studies PHARMACOEPIDEMIOLOGY
focuson
 Global trends inprescribing
 Appropriateness of druguse Demos –
Pharmakon Epi – uponor Logos -
 Medication adherence - Drug among
People or
Study
district
 Identification of predictors
for medication use
Lifestyle effects on drug The application of epidemiologic
therapy knowledge, methods, and
Special population (Elderly, reasoning to the study of the
Pediatric, etc.)drug
therapy effects (beneficial
Drug Interactions and adverse) and use of drugs in
 Predictable ADRs human populations.”
 Uncommon and unpredictable
ADRs
• The International Society for
Pharmacoepidemiology (ISPE) is a non-profit
international professional membership organization
dedicated to advancing the health of the public by
providing a forum for the open exchange of scientific
information and for the development of policy;
education; and advocacy for the field of
pharmacoepidemiology, including
pharmacovigilance, drug utilization research,
outcomes research, comparative effectiveness
research, and therapeutic risk management.
• ISPE convenes an International Conference on
Pharmacoepidemiology each year, as well as a
regional Conference on Pharmacoepidemiology in
Asia
 Taste of Raspberries, Taste of Death The
1937 Elixir Sulfanilamide Incident
• 1932: 1st sulfadrug
• Elixir of Sulfanilamide – chemist Watkin’s creation, a liquidated
sulfanilamide for children.
• 10% sulfanilamide, 72% diethylene glycol (DEG), 16% water, “elixir
flavor”, raspberry extract, saccharin solution, amaranth, and
caramel.
• 107 deaths, 208 survivors.
• Cause of death – Renal failure.
1938: Food, Drug & Cosmetic(FD&C) Act
• Requires new drug pre-marketing safety studies – Origin of what is
now thepharmacoepidemiology
• Prohibits false therapeutic claims
• Authorizes factory inspections
• Allows FDAto request court injunctions (previously: only seizures &
prosecutions)
• Extends control to cosmetics anddevices
• Requires safe tolerances for unavoidablepoisonous substances
1961:Thalidomide tragedy
• introduced in the 1960s
• marketed asContergan®
• used to control nausea inpregnancy
• reports of limbabnormalities
• Dr. William McBride of Australia reported increased frequency of birth defects
(seal limbs) with thalidomide usage, that left 10,000 babies disabled for life.
• Kefauver-Harris Amendments
• “Proof of Efficacy” required
• Adverse events reporting to FDA required
• “Informed consent” for clinical studies
• Drug advertisement must disclose side effects
• 2-year inspection mandate
• Recent data indicate that 100000 Americans die each year from
Adverse Drug Reactions, and 1.5 million US hospitalizations each year
result from Adverse Drug Reactions;
• yet, 20- 70% of Adverse Drug Reactions may be preventable.
• The harm that drugs can cause has led to the development of the
field of pharmacoepidemiology.

Pharmacovigilance is an area unique to pharmacoepidemiology and it

is a type of continual monitoring of unwanted effects and other safety-
related aspects of drugs.
ADR REPORTING
(pharmacovigilance)
• a case report of a patient treated with minoxidil that was
discovered to stimulate the hairgrowth.
• Subsequently a topical formulation of minoxidil was developed to
take advantageof that effect
• Eg: Krishnamoorthy and king reported on the adverse effects
associated with the use of olanzapine in 5 children with severe
behavioural problems.
• Adverse events includes: wt. gain(3/5 children)sedation(2/5
children) and akathisia (2/5 children).
Caseseries
• Advantages
Useful for hypothesis generation
Informative for very rare disease with few established risk
factors
Usually of short duration.

• Disadvantages
Cannot study cause and effect relationships
Cannot assess disease frequency
• Cerivastatin (Baycol), an effective and inexpensive lipid lowering drug,
was introduced in 1997. It was removed from the market in 2001
because of reports of fatal cases muscle breakdown
(rhabdomyolysis).
Cross sectional descriptive study
• Eg: cross-sectional studies was published by Dua and colleagues, who
examined inappropriate sale of antibiotic use in pharmacies in
Nagpur.

• Such studies can identify problem areas and suggest where remedial
action should be directed
DRUG UTILIZATION REVIEW
• Aims to evaluate factors related to the prescribing, dispensing,
administering and taking of medication, and its associated events
(either beneficial or adverse).
• Since the early 1960’s the interest in Drug Utilization Studies has
been increasing, first with market-only purposes, then for
evaluating the quality of medical prescription and comparing
patterns of use of specificdrugs.
• The increasing importance of drug utilization studiesas a valuable
investigation resource in pharmacoepidemiology has been bridging
it with other health related areas, such as public health,
pharmacovigilance, pharmacoeconomics, eco- pharmacovigilance
or pharmacogenetics.
• Drug utilization research is thus an essential part of
pharmacoepidemiology as it describes the extent, nature and
determinants of drug exposure. Incommon use, the distinction
between these two terms has become less sharp, and they are
sometimes used interchangeably.
Insights into the following aspects
ofdrug use and drugprescribing
• Pattern of use:
• extent and profiles of druguse
• trends in drug use and costs over time.
• Quality of use:
• Audits comparing actual use to national and regionalprescription guidelines or
local drug formularies.
• Quality indices of drug use may include the
• choice of drug
• drug cost
• drug dosage
• drug interaction awareness
• ADRawareness
• proportion of patients being aware of/unaware of the cost/benefit of the
treatment, etc.
Special applications of
Pharmacoepidemiology
• Studies of Drug Utilization
• •Evaluating and improving physicianprescribing
• •Drug Utilization Review
• Special methodologic issues in PE studies of Vaccine Study
• •PE studies of Devices
• Studies of Drug induced birth defects
• •PE and Risk management
• •Use of PE tostudy Medication Errors
• •Hospital PE
Impact of pharmacoepidemiology
• population based drug related studies
• rare drug adverse events
• drug efficacy
• drug interactions
• patterns of use
Studying drug interactions in
pharmacoepidemiology
–drug interaction studies usually small human studies
in vitro studies
soft end-points
–usually look at soft outcomes
–clinical significance of interaction-unknown Eg., cimetidine vs. P-450
inhibition
not all interactions clinicallysignificant