Introduction, Definition & Scope

1. Epidemiology is the study of the distribution and determinants of diseases in populations

2. Epidemics is the study of chronic/ infectious diseases in large populations
3. Pharmacoepidemiology is the application of the principles of epidemiology to drug effects
and drug use. Hence, Pharmacoepidemiology is the study of the use of and the effects of
drugs in larger population
4. It involves the examination of a single individual or large groups of people followed for many
years
5. It involves gathering & analysis of information in order to identify possible causation &
related factors, that can be applied in clinical practice to group of people & also to individuals
undergoing treatment.
In general, Pharmacoepidemiology examines the relationship between the drug exposure and health
outcomes in a defined population.

Origin & evolution.

1. ADRs to drugs were as old as modern pharmacotherapy which was developed in 20 th century.
2. Drug resistance, drug abuse & variations in rates of clinical effectiveness were the other
therapeutic problems which emerged.
3. In 1961, the case reports of maternal use of thalidomide with malformations in offspring results in
awareness of the potential for drugs to cause ADRs.
4. Since then, a greater attention was focused on the detection, prevention & management of ADRs
& the era of Pharmacoepidemiology has began.
5. The important ADRs detected through these systems include,
Grey baby syndrome due to Chloramphenicol
Vaginal cancer in off springs of women who took diethylstilbestrol during pregnancy
Isotretinoin induced birth defects
Triazolam induced CNS disturbances
Suicidal ideation with Fluoxetine
Deaths with Fenoterol
Venous thromboembolism with OCs.
6. ISPE was formed, to obtain more data on risk & benefits of drugs in population and to discuss,
develop & disseminate information about Pharmacoepidemiological methods
7. In early 1960, the related field of drug utilization was developed along with the study of ADRs
8. Previously, DU studies were conducted mostly for marketing purposes and data were not
available for use by health authorities
9. As a result of wide variations in the pattern & extent of drug prescribing, growing concern about
ADRs & cost of the drugs, the Pharmacoepidemiological methods were developed
10. According to WHO, DU is the marketing, distribution, prescription & use of drugs in a society
with special emphasis on the resulting medical, social & economic consequences
11. In Europe, DU research developed at the national & international level with a common
methodology for comparative DU studies using a relatively economic & readily available drug
statistical sources

In NA, DU research was developed on a smaller scale & was most emphasized on the qualitative
aspects of prescribing (antibiotics)
12. DUR is an authorized, structured & continuing program that reviews, analyses & interprets
patterns of drug use against predetermined standards
13. In Europe, the medical audit concept was implemented & was defined as a searching
examination of the way in which drugs are used in clinical practice carried out at intervals
frequent enough to maintain generally accepted standard of prescribing
14. It was mainly focused on medical practitioners with aim of improving the Rational Drug
Usage(RDU)
Why Pharmacoepidemiology?
1. Lack of alternative models to investigate some drug events
E.g.: to evaluate teratogenic effects of a new medicine
2. Clinical Trials (CTs) are inadequate to answer questions about drug safety, as they lack adequate
statistical power
3. If at all adequate for establishing effectiveness, the sample size are inadequate to detect less
common ADRs
4. CTs are conducted on highly selected patients without any co-morbidities & who taking no other
medications.
5. CTs does not involve elderly, paediatric or pregnant patients
6. CTs investigate the single indication
7. Hence, CTs fail to provide adequate information related to safety & efficacy of a drug under nontrial conditions & in other indications
In contrast, Pharmacoepidemiological models provide alternative approaches to evaluate drug
effects.
Aims of PEY
1. Signal generation:
Identification of new, sometimes serious ADRs
Also helps to detect new applications of a drug
Ex: Minoxidil is used as Antihypertensive and Hirsutism
2. Risk quantification:
PEY models can be applied for risk quantification which make use of The rule of three
indicates if an event occurs in 1 of every 5000 exposed persons, 3 5000, People would be
needed in a sample to be 95.
3. Hypothesis testing:
It requires the use of comparison groups to determine whether there are differences in
variables of interest

Applications of PEY
1. Estimation of the risks of drug use:
The risk involved in drug use can be quantified
The benefits & risks of use of a drug may be weighed

Risk estimation also helps to identify risk situation

Ex:
Case reports of triazolam induced psychiatric disturbances appeared soon after its
introduction to market
The drug was withdrawn in some countries . The reaction was likely due to dose related,
hence the problem was abated by recommending a lower dose
2. Use in patient counseling:
Collection & analysis of observational data from other studies may help to address
certain issues through counseling the patients
Ex: A pregnant patient may wish to terminate pregnancy if there is a substantial risk for
producing a seriously malformed child, but would also wish to proceed with the pregnancy if
the risk is low.
3. Formulation of public health policy decisions:
Qualitative as well as quantitative information from PEY studies helps to address many
issues
Ex: If an inappropriate prescribing is observed among prescribers, regulatory agencies
may require educational intervention or may impose restrictions on specific drugs or on
practitioners
PEY studies also helps the policy makers to assess whether a drug should be withdrawn from the
market or allowed to remain
4. Facilitation of pharmacoeconomic evaluations:
Data from PEY studies can be used to measure the effects of drugs on overall health care costs &
resource consumption
Ex: Hospitalization due to serious adverse effects of a drug leads to more expenses as well as
resource consumption, which could be avoidable.