Pharmacoepidemiology involves applying epidemiological methods to study drug use and effects in large populations. It is primarily concerned with post-marketing drug safety surveillance but also analyzes patterns of drug use and assesses effectiveness. Pharmacoepidemiological studies use large healthcare databases and are important for identifying adverse drug reactions, determining risk factors, and improving appropriate medication use. Common study designs include cohort studies, case-control studies, and randomized controlled trials. Pharmacoepidemiology plays a key role in drug regulation, marketing, clinical practice, and public health policy.

1. Pharmacoepidemiology
Dr Lateef M Khan

2. Introduction
Application of epidemiological methods to the clinical use and
effects of drugs in a large population is called as
Pharmacoepidemiology.
Pharmacoepidemiology was primarily concerned with post-
marketing studies of drug safety.
Pharmacoepidemiology research is often based on large health care
utilization databases using non experimental study of intended and
unintended drug effects outside of randomized controlled trials.
In addition to identifying adverse events, one of the key objectives of
Pharmacoepidemiology is to identify reasons that may explain the
adverse events. These questions can include:
Pharmacoepidemiology.

3. Are the events dose related?
Does the pharmaceutical interact with other
medications or substances to promote adverse events?
Are there high-risk subpopulations or pertinent
lifestyle factors that can be identified as being related to
the event?
Are drugs being used differently than originally
intended

4. Furthermore, it also define patterns of physicians’ prescription and
patients’ use and compliance of medications.
Analyze the influence of health system factors (policies, coverage
and reimbursement differences) on the quality of medication use.
Design, implement, and test innovative programs to improve the
appropriateness of medications prescribed by physicians and used
by patients.

6. Short duration Premarketing studies are limited in time. Effects that develop
following chronic use or those that have a long latency period
cannot be detected
Small sample size Few drugs are studied in more than 4,000 subjects before FDA
approval. Effects that occur with a frequency of less than
1/1,000 are difficult to detect.
Narrowly defined
population
Premarketing studies generally do not include special
populations such as children, women of childbearing
age, or the elderly.
Narrow set of
indications
Manufacturers pursue specific indications for use during
premarketing studies.
Limited
comparison
groups
The comparison group is often limited to placebo.
Limitations of Premarketing Clinical Trials

7. • About 20% of drugs get new “black box”
warnings after marketing
• About 4% of drugs are ultimately
withdrawn for safety reasons
Consequences of Limitations of Pre-marketing
Trials

8. •Suicidal tendency increased tendency associated to the use of fluoxetine and other
SSRI antidepressants
•Tardive dyskinesia associated with long-term use of metoclopramide and many
antipsychotic
•Stroke or heart attack associated with sildenafil (Viagra) when used with
nitroglycerine
•Cerivastatin. Treatment of hypelipdeimeia
•Introduced in 1990s, withdrawn in 2001
•Why ? , 52 deaths were reported from rhabdomyolysis and its resultant renal
failure
•The story of thalidomide is well known
•Chloramphenicol and Grey Baby Syndrome
•Gynaecological cancer in offspring of women receiving Diethyl Stilboestrol
•Oculomucocutaneous syndrome with practolol
•Liver disease from benoxaprofen
•Valvular heart disease from Dexfenfluramine
•Cardiac arrhythmias with terfenadine
Despite the rigorous process for drug approval and regulation, several
important medications have been removed from the market because of serious
ADEs over the past 30 years as a result of Pharmacoepidemiological studies

9. Pharmacoepidemiological consulting services on numerous projects
also provided supportive evidences. Some examples include:
Cardiovascular risk among women using dietary supplements
Liver failure risks among users of anticonvulsants
Clinical and economic impacts on asthma and COPD of a new
respiratory bronchodilator
Costs associated with complications after cataract surgery
Effectiveness of adding omega-3 supplements to diet
Projection of future needs, clinical trends, and economic impact for
knee and hip replacement surgery
Assessment of potential patient population size for proposed orphan
drug application and filing of Pediatric Investigation Plan
Epidemiologic evaluation of factors influencing patterns of care in
chemotherapy treatment for common female cancers,
Beneficial findings of Pharmacoepidemiological studies

10. Aim of Pharmacoepidemiology
• Signal Generation: Most commonly associated with
ADR but also use to detect new applications
– E.g Minoxidil 1st indicated for hypertension but
case report (signal generation) soon identified it
causes hirsutism in a number of patients, side
effect was investigated and now it is marketed for
purpose mainly stimulation of hair growth
• Risk Quantification: of ADR often require large
sample size

11. Hypothesis testing
Require the use of comparison group to determine
whether there are difference in variable of interest (risk
factor, trait, characteristic, drug exposed, or clinical
conditions)
Statistical methods are used to assess whether the
observed difference could have occur by chance alone
 Conclusions about relation b/w exposure to a drug and
clinical event thus based on the ability to reject the null
hypothesis, postulating that the 2 group are no difference
with regard to either the drug exposure or the clinical
event

12. Example: Signal identified via spontaneous reporting
confirmed by a formal Pharmacoepidemiology study.
Background-
•Phenylpropanolamine (PPA)- ingredient used in OTC and
prescription cough and cold medications as a decongestant, and
in OTC weight loss products.
•In 1984, FDA received reports of Hemorrhagic stroke (bleeding
into brain or into tissue surrounding brain) in association with
PPA.
•In addition, there were published reports in literature.
•Question-
•Is the use of PPA-containing products associated with
hemorrhagic stroke?

13. Approach-
To confirm this signal, an ad-hoc case-control study was
conducted
Results
The study demonstrated a statistically significant increased risk of
hemorrhagic stroke among both appetite suppressant users and
first-time users of PPA as cough/cold remedy
Outcome-
FDAAdvisory Committee meeting discussed the case-control
study and recommended that PPA be considered not safe for
OTC use
FDA then took steps to remove PPA from all drug products and
requested all drug companies to discontinue or reformulate PPA-
containing products.

14. Reasons to perform PE studies:
(A) Regulatory
(1) Required to obtain earlier approval for marketing
(2) As a response to question by regulatory agency
(3) To assist application for approval for marketing elsewhere

15. (B) Marketing
(1) To assist market penetration by documenting the safety of the
drug
(2) To increase name recognition
(3) To assist in repositioning the drug
(a) Different outcomes, e.g., quality-of-life and economic
(b) Different types of patients, 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

16. (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 identify the frequency of adverse reactions
(2) Hypothesis generating—need depends on:
(a) whether 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

17. Thus, the decision to conduct a PE study can be viewed as similar
to the regulatory decision about whether to approve a drug for
marketing or the clinical decision about whether to prescribe a
drug.
In both cases, decision making involves weighing the costs and
risks of a therapy against its benefits.

18. Application of Pharmacoepidemiology
• Estimation of risk of drug use
• Use in patient counseling
• Formulation of public health policy decision
• Formulation of therapeutic guidelines and discovery
of new indications
• Facilitate thepharmaco-economic evaluation

21. Pharmacoepidemiology in Practice
• The basic idea of pharmacoepidemiology is to
measure the source, use, and effects of drugs in a
population and to determine the frequency and
distribution of drug use outcomes in that population

22. The focus of this type of research includes
(1) what is being used (an assessment of specific
drugs being used in certain situations)
(2) How it is being used (an assessment of the
patterns of use, including how much, where and
when, and by whom); and
(3) Why it is being used (an assessment of the reasons
for drug-taking behaviors and the functions that
drugs serve in society).

23. World Health Organization
WHO focuses its pharmacoepidemiological efforts on ensuring the
quality, safety, and efficacy of drugs and their use in specific
populations and studies are performed to :
1) Describe current patterns of drug use in specific patient
populations
2) Determine changes in drug use over time
3) Measure the effects of information, education, promotional
activities, media accounts, and price on drug use
4) Detect inappropriate drug use and associated problems
5) Estimate drug needs in terms of disease patterns and outbreaks
6) Plan the selection, supply, and distribution of drugs.

24. Research methods used most often by
pharmacoepidemiologists
• Cross-sectional study: a prevalence survey of health
and illness in the population at one point in time
• Case-control study, a retrospective analysis comparing
subjects with the condition (cases) to those without it
(controls) with respect to possible risk or causative
factors
• Cohort study, an incidence study that follows a
population free of health problems over time,
examining subsequent development of problems and
factors associated with them.
• Clinical trials, an experimental approach that tests the
value of a new treatment or intervention compared
with a standard treatment or a placebo, are also
considered to be an epidemiological method

25. Thus, Pharmacoepidemiology relies on the same study designs
(cohort, case control, case-crossover, case-cohort studies), as other
branches of epidemiology.
The field also offers unique challenges in:
 Controlling For Confounding Factors
Addressing The Limitations Of Health Care Databases
 Obtaining Accurate Assessment Of Drug Exposure And Use
 Accounting For Potential Selection Bias Concerns.
Common research methods used by Pharmacoepidemiologists –
Cont’d
Moreover, Pharmacoepidemiological studies provide "real
world" assessments of potential short-term and long-term
adverse drug events in the general population with a wide range
of health status and demographic characteristics and with a
much longer follow-up period than clinical trials, which
evaluate initial drug efficacy and safety.

26. Sources of Data on Drug Use
• Institutional record systems and databases
– Drug utilization studies
– Hospital-based medical audits (inpatient)
• System wide databases
– Institutionally based reviews (outpatient)
– Health insurance groups and third-party payers
– Pharmaceutical organizations
– Commercial vendors of marketing studies and
sales data

27. • National databases
– government-sponsored studies
– essential drug lists and inventory data
– pharmacoepidemiological surveillance systems
• Field data
– records of drug dispensers, sellers, and distributors
– drug-taking behaviors of individuals and small
groups
• Experimental data
– clinical trial results
Sources of Data on Drug Use- Cont’d

28. Problem Solving with Pharmacoepidemiology
Medical drug use
 Beneficial effects of drug therapy
 Risks (e.g., adverse reactions, side effects) of drug
therapy
 Inappropriate prescribing behaviours
 Patient noncompliance
 Irrational self-medication practices
 Poor drug use outcomes
 Cost-effectiveness of drug therapy

29. Problem Solving with Pharmacoepidemiology- Cont’d
Nonmedical drug use
Social-recreational drug use and associated
problems
Acute incidents of drug toxicities (e.g., overdoses)
Chemical dependencies
Outbreaks and sources of drug epidemics

30. Conclusion
All drugs have adverse effects and Pharmacoepidemiology will
never succeed in preventing them.
It can only detect them, hopefully early, and thereby educate health -
care providers and the public, which will lead to better medication
use.
The net results of increased activity in pharmacoepidemiology will
be better for industry and academic world but, most importantly, for
the public’s health.
The next drug disaster cannot be prevented by
pharmacoepidemiology. However, pharmacoepidemiology can
minimize its adverse impact by detecting it early.
The past few decades have demonstrated the utility of this new
field.
With good fortune, the next few years will see the utility is
accentuated and the problems will be improved.