Pharmacoepidemiology is the study of the use and effects of drugs in large populations. It combines clinical pharmacology and epidemiology to study drug use, benefits and risks. Pharmacoepidemiology uses observational studies, experimental studies, and quantitative synthesis to generate and test hypotheses about drug risks and benefits. Common study designs include cohort studies, case-control studies, randomized controlled trials, meta-analyses and decision analyses. Pharmacoepidemiology aims to optimize the benefit-risk balance of drugs.

1. PHARMACOEPIDEMIOLOGY (PE)
PREPARED BY: MRS. SHITAL REVAN KALEKAR
ASSISTANT PROFESSOR
YADAVRAO TASGAONKAR INSTITUTE OF
PHARMACY, CHANDAI, BHIVPURI ROAD, KARJAT,
MAHARASHTRA, INDIA

2. Contents
• Definitions of PE
• What is PE?
• Evolution of PE
• Introduction
• Reasons to perform PE studies
• Study designs of PE
• Drug utilization study
• Applications of PE

3. Definitions of PE
• “The study of the use and effects of medications in large
numbers of people.” (By Strom)
• “The application of epidemiologic knowledge, methods and
reasoning to the study of the effects (beneficial and adverse)
and use of drugs in human populations.” (By Porta and
Hartzema)
• “The study of drugs as determinants of health and disease in
the general unselected ppopulation.” (By Spitzer)

4. What is PE?
• Pharmacoepidemiology is the application of epidemiologic
knowledge, methods, measurements, analysis, and reasoning to
study the uses, beneficial and adverse effects of drugs
(including biologics, vaccines, and therapeutic devices) in
defined human populations.
• Pharmacoepidemiology integrates with therapeutic risk
management to minimize risks throughout the whole life cycle
of a drug (i.e., from the time when it is first discovered or
synthesized until it is no longer sold as a drug), and optimize
its benefit/risk balance.

5. Evolution of PE
• Each year in America due to medicinal side effects 100,000
people lose their lives and 1.5 million people are hospitalized.
It has been stated that 20 to 70 % of these hospitalizations are
preventable cases.
• These disservices caused by medicinal side effects have
resulted in the development of the field of
pharmacoepidemiology which investigates drug use by, and
medicinal effects on, large numbers of people and drug costs.

6. INTRODUCTION
• Pharmacoepidemiology is the study of the use and effects of drugs in large
numbers of people.
• Pharmacoepidemiology combines clinical pharmacology with epidemiology.
• Pharmacology is the study of the effects of medications in humans. It
pertains to using pharmacokinetics and pharmacodynamics of a patient to
predict the drug effect on a patient.
• Epidemiology is the study of the factors that determine the occurrence and
distribution of diseases in populations. Epidemiologists study how much
disease is in a given area, who gets it, and what specific factors put
individuals at risk. Epidemiology can often be divided into infectious and
chronic disease epidemiology.
• By combining the interest of pharmacology and epidemiology, a
pharmacoepidemiologist applies epidemiology principles to study the effects
of medications in human populations.
• Pharmacoepidemiologists make use of epidemiological causes, methods and
knowledge to increase drug benefits and decrease risks.

7. Reasons to perform
pharmacoepidemiology studies
(A) Regulatory
(1) Required
(2) To obtain earlier approval for marketing
(3) As a response to question by regulatory agency
(4) To assist application for approval for marketing elsewhere
(B) Marketing
(1) To assist market penetration by documenting the safety of the drug
(2) To increase name recognition
(3) To assist in re-positioning the drug
(a) Different outcomes, e.g., quality of life and economic
(b) Different types of patient, e.g., the elderly
(c) New indications
(d) Less restrictive labeling
(4) To protect the drug from accusations about adverse effects
(C) Legal
(1) In anticipation of future product liability litigation

8. Reasons to perform
pharmacoepidemiology studies
D) Clinical
(1) Hypothesis testing
(a) Problem hypothesized on the basis of drug structure
(b) Problem suspected on the basis of preclinical or premarketing human data
(c) Problem suspected on the basis of spontaneous reports
(d) Need to better quantitate the frequency of adverse reactions
(2) Hypothesis generating- need depends on whether
(a) it is a new chemical entity
(b) the safety profile of the class
(c) the relative safety of the drug within its class
(d) the formulation
(e) the disease to be treated, including
(i) its duration
(ii) its prevalence
(iii) its severity
(iv) whether alternative therapies are available

9. Types and methods(Study design) of
Pharmacoepidemiology
• PE/ Epidemiological studies can be divided into two types:
1. Observational study
A. Descriptive study
a. Case report study
b. Case series study
c. Cross sectional study
d. Ecological study
B. Analytical study
a. Case control study
b. Cohort study
2. Experimental/Interventional study
a. Randomized control trial or clinical trial
b. Non randomized trial
1. Field trial
2. Community trial
C. Quantitative synthesis study
1. Meta analysis study
2. Decision analysis study

11. Observational VS Experimental
Studies
• Observational studies: Allow nature to take its cause; the investigator measures
but does not intervene
• Descriptive study: focuses on the description of the occurrence of a disease in a
population
• Analytical study analyses relationships between health status and other variables
• Experimental studies involve an active attempt to change a disease determinants
(e.g. an exposure or a behaviour) or the progress of a disease (through treatment)
• The studies are based on a group which has had the experience compared with
control group which has not had the experience.
• Observational studies are operationally simple, shorter in time duration and less
costly as compared to experimental studies.
• Observational studies are useful to prove the effectiveness of drugs at times
e.g. the pivotal study conducted on 30,569 patients in Canada that assessed the
effect of corticosteroids in asthma, which showed 21% less mortality in the
patients who were given corticosteroids.

12. Purpose of descriptive epidemiology
• To generate hypothesis
• To permit evaluation of trends in health and disease and
comparisons among countries and subgroups within countries.
• To provide a basis for planning, provision and evaluation of
health services
• To identify problems to be studied by analytical methods and
to suggest areas that may be fruitful for investigation.

13. Case report and case series
• Case reports: documents unusual medical occurrence and can
represents the first clues to the formulation of hypothesis , generally
report a new or unique findings and previous undescribed disease. It
is an event seen in single patient.
• Ex. Zappacosta presented a case report of a patient treated with
minoxidil that was discovered to stimulate the hair growth.
Subsequently a topical formulation of minoxidil was developed to
take advantage of that effect.
• Case series: collection of individual case reports which may occur
within fairly short time and experience of a group of patients with
similar diagnosis.
• Ex. Krishnamoorthy and king reported on the adverse effects
associated with the use of Olanzapine in 5 children with severe
behavioural problems . Adverse events includes: weight gain in 3/5
children, sedation in 2/5 children and akathisia in 2/5 children.

14. Case series
• Advantages :
1. Useful for hypothesis
generation
2. Informative for very rare
disease with few
established risk factors
3. Usually of short duration
• Disadvantages
1. Cannot study cause and
effect relationships
2. Cannot assess disease
frequency

15. Cross sectional study
• It is also called prevalence study
• It describes data collected on a group of subjects at one point
in time rather than over a period of time i.e. they survey
exposure and disease at a single point in time.
• Both exposure and outcome and variables are been evaluated
at the same point in time(without any inbuilt directionality).
• Study the distributions of drug use and disease in a
populations.
• Most sophisticated descriptive study.
• It answers the question “what is happening right now?”
• There is no direction of enquiry.

16. Cross sectional study
• Ex. 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.
• Advantages:
o Relatively quick
o Inexpensive
o Valuable to estimate prevalence of drug use and disease
• Disadvantages:
o Only snapshot at a time leading to a misinformation.
o Response rate may be low, with result not representative of
the population

17. Ecological studies
• It is also called as analyses of secular trends (or correlational studies).
• It examine trends in exposure (drug use) and outcomes when they
coincide over time for groups (i.e., communities, countries or population
level) or across geographic boundaries.
• The measure of association for an analysis of secular trends is
correlation.
• Measures that represent characteristics of entire populations are used to
describe the disease in relation to some factor of interest (such as age,
calendar time, food consumption, drug use and utilization of health
services)
• Analyses for secular trends are useful for rapidly providing evidence for
hypothesis generation and preliminary research.
• For example, Dales et al. conducted a study in California, US to
determine if a correlation exists between measles-mumps-rubella (MMR)
immunization coverage among young children and autism occurrence
between 1980 and 1994. The study did not find a positive correlation
between MMR immunization and autism occurrence among young
children.

18. Ecological studies
• Advantages:
o Can provide rapid answers
o Relatively quick and inexpensive
o Compares events among nations
• Disadvantages:
o No control of confounding
o Ecologic fallacy: doesn’t compare individuals, so it might lead
to overgenerallization
o Changes in diagnosis, coding systems overtime

19. Analytical studies
• It is type of observational study
• To test hypothesis
• There must be a comparison group
• No control no conclusion (NCNC)
• Two basic designs:
 Case control or retrospective study
 Cohort or prospective study

20. Case control study
• Case-control studies are analytic observational studies that compare
cases with a disease (or an adverse event) to controls without the
disease, looking for differences in preceding drug(s) use.
• The common sources for selecting cases with the outcome of interest
include case-control surveillance and registries.
• It is critical to select representative controls that have the same risk of
exposure as cases.
• Poor choice of controls can lead to both wrong results and possible
medical harm.
• Controls can be recruited from known or unknown study populations
(or study group or base).
• For example, since endometriosis needs an operation for the
diagnosis, investigators frequently select women having laparoscopy
or laparotomy without diagnosis of endometriosis. But women
having operations are unlikely to be representative of all those at risk
of developing endometriosis, since operations do not occur at
random.

22. Case control study
• Advantages:
o Can study multiple
exposures
o It is rapid, inexpensive and
relatively easy to carry out
o It requires comparatively
few subjects
o There is no risk to the
subjects.
o It can assist one in studying
different etiological factors.
o One does not need an
ethical clearance.
• Disadvantages:
• It introduces bias
• It may be difficult to
distinguish between the
cause of a disease and an
associated factor.
• To select an appropriate
control could be difficult.
• Recall limitation, recall
bias, selection bias,
temporal bias

23. Cohort study
• Cohort studies are essential to pharmacoepidemiology since they
form the basis for the quantification of drug risk and benefit
assessments.
• These studies identify subsets of a defined population, based on the
presence or absence of a particular drug use, and follow them over
time, looking for differences in the outcome of interest.
• Cohort studies generally are used to compare drug-exposed patients
to unexposed patients, but they can be used to compare one drug use
to another drug or treatment.
• The major sources of information about drug exposures are billing
claims or automated databases, physicians (e.g., sent questionnaires
in the prescription event monitoring in UK), pharmacies (e.g.,
pharmacy-based surveillance), and self-reports from patients.
• Cohort studies can be performed prospectively, retrospectively or
ambispectively.

24. Cohort study design

25. Cohort study design
• Advantages:
oThere is no bias
o Risk can be calculated
because the incidence
can be calculated
o Effective for studying
rare exposures
o Allows the study of the
natural history of the
disease
o Assists in determining
the temporal relationship
between the etiological
factor and the disease
• Disadvantages:
o It takes a long time
o It is expensive
o Large number of subjects
are needed
o There could be changes in
the standard methods or
diagnostic criteria
o Time-consuming if done
prospectively

26. Experimental studies
• Studies in which one group is deliberately subjected to an
experience compered with a control group with similar
experience
• The gold standard in medicine because it proves causality
• Can be controlled or uncontrolled

27. Uncontrolled experimental study
• Intervention is not compared with a control
• The aim is to confirm that the intervention made a difference

28. Controlled experimental study
• In this study, a drug or procedure is compared to:
1. Another drug
2. Procedure
3. Placebo
4. Previously accepted standards for treatment
5. The aim is to prove the difference due to standards for
treatment

29. Experimental study design

30. Randomized control trial
• A RCT is an experimental study in which investigators control
the intervention and randomly allocate patients among the
study groups.
• The major strength of this approach is random assignment,
which is the only way to ensure that the study groups are
comparable in potential unknown or unmeasurable
confounding variables.
• RCTs are considered to be the most scientifically rigorous
method for hypothesis testing.
• RCTs are emerging as a part of post-marketing surveillance.
• Allow to estimate absolute risk.

31. Randomized control trial (RCTs)

32. Experimental study design
• Advantages:
• Best study type
• Greatest prove of causality
• Gold standard for other
design
• Least bias
• Proves best standard for
treatment or procedure
efficacy
• Disadvantages:
• Long duration
• Most expensive
• Limited generalizability
• Logistically most difficult
• Ethical objections for
proven therapies

33. Quantitative synthesis study
• Meta-analysis and decision analysis have in common that they
synthesized knowledge.
• Each method takes parts of the medical literature or clinical
experience and, based on this information, attempts to create a
whole answer to a defined problem.
• In addition, they are quantitative, using statistical and
numerical analysis, aims to resolve uncertainty and facilitate
decision making.
• Each plays a prominent role in the formulation of clinical and
public policy in health care.

34. Meta analysis study
• Characteristics:
o Aims to resolve uncertainty and facilitate decision making
o Systematically assess and combine the results of previous
studies in order to draw conclusions about the body of research
• Measures of association:
o For RCTs: Absolute risk (Number needed to treat/Number
needed to harm), Relative risk;
o For observational studies: Relarive Risk or Odds Ratio
• Main Application/Ex.:A meta-analysis on the effectiveness and
safety of atypical antipsychotic medications for off-label uses
in adults

35. Meta analysis study
• Advantages:
o Increasing sample size and
power to detect benefits
and harms
o Good source for evidence
based clinical decision
making
o Ability to assess subgroups
effects and rare events
o Save time/resources/
money
• Disadvantages:
o Susceptibility of the
original studies to bias
o Publication bias,
dissemination bias
o Practical difficulties of
combining results
o May have paradoxical
results
o Potential biased results
from manipulation of study
selection and analytic
strategies

36. Decision analysis study
• Characteristics:
o Aims to resolve uncertainty and facilitate decision making •
o 4 types of economic decision analyses: costminimization,
costbenefit, costeffectiveness, and costutility analyses.
• Measure of association:
o Incremental Cost Effectiveness Ratio (ICER)for cost
effectiveness analysis; International Cost Utility Ratio (ICUR)
for cost-utility analysis
• Ex. A cost-utility analysis of the effects of aspirin therapy,
statin therapy, combination therapy with both drugs, and no
pharmacotherapy for the primary prevention of CHD events in
men

37. Decision analysis study
• Advantages:
• Assist health care
professionals having a better
understanding the risk-benefit
trade-off of different treatment
options
• May incorporate patients’
values into decision when
utilities are obtained from
patients (e.g., visual analog
• Disadvantages:
• Difficult to represent all
choices and chance
occurrences in the model
• Patients cannot experience
multiple outcomes at the
same.
• May require some events only
occur for a set and limited
amount of time
• Obtaining utilities from
patients can be challenging
• The assumptions which were
made from the diverse and
imprecise data influence the
quality and results

38. Drug utilization study
• It aim 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, 1st with market then for evaluating the
quality of medical prescription and comparing patterns of use
of specific drugs.
• The increasing importance of drug utilization studies as a
valuable investigation resource in PE has been bridging it with
other health related areas, such as public health,
pharmacovigilance, pharmacoeconomics, eco-
pharmacovigilance or pharmacogenetics.
• Drug utilization research is thus as essential part of PE as it
describes the extent, nature and determinants of drug exposure.

39. Drug utilization research and PE provide insights into the
following aspects of drug use and drug prescribing:
• Pattern of use: Extent and profiles of drug use and trends in drug use
and costs over time
• Quality of use: audits comparing actual use of drug to national ad
regional prescription guidelines or local drug formularies. Quality
indices of drug use may include the choice of drug (compliance to
recommended assortment), drug cost (compliance to budgetary
recommendations), drug dosage (awareness of inter individual
variations in dose requirements and age dependence), drug
interaction awareness, ADR awareness, proportion of patients being
aware of/ unaware of the cost/ benefit of the treatment, etc.
• Outcome of use: Health outcomes (benefits and adverse effects) and
economic consequences.
• Determinants of use: User characteristics (e.g. socio-demographic
parameters, attitude towards drugs), prescriber characteristics (e.g.
specialty, education and factors influencing therapeutic decisions),
and drug characteristics (e.g. therapeutic properties, affordability)

40. Applications of PE
• PE studies are useful to take regulatory decisions and are often
required by regulatory agencies to answer specific queries.
• PE studies support market penetration by documenting the safety of
the drug and protect the drug from “accusations” about adverse
effects.
• They also support marketing strategies to increase name recognition
and assist in repositioning the drug (e.g., quality-of-life and economic
advantages, effects in special populations, or study of new
indications).
• PE studies are performed in anticipation of future product liability
litigation.
• Use of PE to study medication errors
• Studies of drug utilization
• Evaluating and improving physician prescribing
• Studies of drug induced birth defects
• PE studies of vaccines and devices

41. References
• Parthasarthi, “A Textbook of Clinical Pharmacy Practice”,
Edition-2001, page no. 466-482
• Stanley K. Design of randomized controlled trials. Circulation.
2007 Mar 6;115(9):1164e1169. 2.
• Guidance for Industry Good Pharmacovigilance Practices and
Pharmacoepidemiologic Assessment available on
http://www.pharmacoepi.org/riskmgmt/fda_pv-pharmacoepi_
050324.pdf
• Hennessy S. Post marketing drug surveillance: an
epidemiologic approach. Clin Ther. 1998
• Strom BL, Kimmel SE. Textbook of Pharmacoepidemiology.
West Sussex, England: John Wiley & Sons Ltd; 2006.