Epidemiology is the study of occurrence, distribution and determinants of health and diseases

or disorders in man and its applications in controlling health problems. Clinical Pharmacy is
the study of effect of drugs in humans. The core of pharmacoepidemiolgy lies at the
intersection of clinical pharmacology and pharmacoepidemiolgy
DEFINITION:
The term Pharmacoepidemiology first appeared in the medical literature in a British Medical
Journal editorial by Lawson in 1984. Pharmacoepidemiology is the study of the use and
effect of medicines in large number of people. It falls within the area of clinical
pharmacology and epidemiology and can be seen as the application of principles of
epidemiology to drug effects and drug use. The focus of studies may range from a single
individual (as in case reports of a rare ADR) to huge group of people being followed for
several years.

ORIGIN & EVOLUTION:

As the modern effective drugs became increasingly available and used in large populations,
there was concomitant increase in realisations of their potential for producing ADRs as well
as other therapeutic problems including drug resistance, abuse and variations in clinical
effectiveness.
The

traditional

clinical

pharmacology

was

focussed

on

pharmacokinetics

and

pharmacodynamics of drug covering ADME of the drugs. Such studies usually involves small
number of people and often ranges from 6 to 25and were conducted mainly for determining
the frequency of administration of new drugs in the treatment of patients. They were mainly
aimed at approval processes of new drugs and were of little use in providing information
regarding new medicines after their marketing.
In 1906, the US law- the Pure Food and Drugs Act was passed in response to excessive
adulteration and in 1937, over 10 children died due to renal failure caused by sulphanilamide
syrup marketed by Massengil Company leading to the passing of Food, Drugs and Cosmetics
act in 1938. However, not much attention was paid to the adverse events of drugs until early
1950s, when it was found that chloramphenicol could cause aplastic anemia

Thalidomide tragedy (1961): Thalidomide was marketed under the name Countergan and was
used as a sleeping pill devoid of the serious side effects of barbiturates. Maternal use of
thalidomide lead to foetal malformations. Though it was not the first drug to cause ADR, it
brought into attention the seriousness of the events and attention was focused from thereon to
the detection, prevention and management of ADRs. It was epidemiological studies which
established the relationship between the syndrome and in-utero exposure to thalidomide. It
lead to the beginning of era of Pharmacoepidemiology.
Different countries have evolved different surveillance system to identify ADRs and results
of such system have led to identifications of Grey baby syndrome associated with
Chloramphenicol, vaginal cancer in adolescent offspring of women who took
diethylstilboestrol during pregnancy.
Recent events of concern: association of birth defects with isotretinoin, CNS disturbance
with triazolam, suicidal identification with fluoxetine, VTE with OCAs.
In some situations, these drugs have either been re-introduced or reserved for special
situations.
Eg: Clozapine: at the time of withdrawal, it was estimated to cause agranulocytosis in 1 in
every 5000 patients and later was found to produce severe neutropenia in 1 in 200. But this
was a manageable risk and clozapine was found to have unique benefits. Summarising, the
risk size was so low that the relevance of withdrawal was questioned.
Sometimes drugs which are having negative risk-benefit ratio are left to remain in market due
to lack of data to warrant their removal
To discuss, develop and disseminate information about pharmacoepidemiological methods,
an international society called the International Society for Pharmacoepidemiology (ISPE)
was formed.
The virtual explosion in the marketing of new drugs, the wide variation in the patterns and
extent of prescribing, the growing concerns about ADRs and the cost of drugs lead to the
development of field of drug utilization.
According to WHO, drug utilization is the marketing, distribution, prescription and use of
drugs in a society, with special emphasis on the resulting medical, social and economic
consequences.

Drug utilization review has been defined as an authorized, structured and continuing
programme that reviews, analyses and interprets patterns of drug use against predetermined
standards.
Audit in drug use is defined as a searching examination of the way in which drugs are used
in clinical practice carried out at intervals frequent enough to maintain a generally accepted
standard of prescribing.
SCOPE OF PHARMACOEPIDEMIOLOGY
Observational methods used in pharmacoepidemiolgy helps in:

investigation of some drug events which are not possible by other means as in case of

pregnancy.
Detecting less common ADRs as RCTs are not powerful enough statistically to

answer questions about drug safety.

Establishing safety of drugs in non-trial conditions as in case of patients with renal

and hepatic failureS

Retrospective analysis utilizing more than single source of data

(A) Information which supplements the information available from premarketing studies
better quantitation of the incidence of known adverse and beneficial effects
(a) Higher precision
(b) In patients not studied prior to marketing, e.g., the elderly, children, pregnant women
(c) As modified by other drugs and other illnesses
(d) Relative to other drugs used for the same indication
(B) New types of information not available from premarketing studies:
(1) Discovery of previously undetected adverse and beneficial effects
(a) Uncommon effects
(b) Delayed effects
(2) Patterns of drug utilization
(3) The effects of drug overdoses
(4) The economic implications of drug use
(C) General contributions of pharmacoepidemiology:

(1) Reassurances about drug safety

(2) Fulfillment of ethical and legal obligations