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PHARMACOEPIDEMIOLOGY
PHARMACOVIGILANCE
Valentina Meta Srikartika, S. Farm, MPH, Apt

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PHARMACOEPIDEMIOLOGY
A BRIEF INTRODUCTION

PHARMACOEPIDEMIOLOGY
DEFINITION
n

Pharmacoepidemiology is the study of the use and effects of

drugs in large groups of people

Clinical
Pharmacology

Epidemiology

Pharmacoepidemiology

PHARMACOEPIDEMIOLOGY
AND OTHER DICIPLINES

THREE MAIN ISSUES

n

What is the drug use in a spesific population?

What are the determinants of drug use?

What are the outcomes of drug use (beneficial and adverse

effects)?

THE CONCEPT
DETERMINANTS

DRUG USE

HEALTH STATUS/
OUTCOMES

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DETERMINANTS

DRUG USE

Information on drug use in a spesific population

Contoh:
n
n
n
n

Pola peresepan
Pola kepatuhan pengobatan
Pola peresepan rasional
Pemilihan obat OTC

Sumber data:
n

Prescribers

Dispensers
Drug user

HEALTH STATUS/
OUTCOMES

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DETERMINANTS
n

DRUG USE

HEALTH STATUS/
OUTCOMES

Knowledge about the factors that determine drug choice or

adherence to drug is ESSENTIAL
RATIONAL

DRUG USE
INTERVENTION in drug use can be adequately targeted
n

For examples:
n

Why adolescents are less likely to adhere their insulin therapy

than other diabetic patients

Why women use more benzodiazepines than men

Etc

Age, gender, socioeconomic status, etc

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DETERMINANTS

and adverse effects

For examples:
n
n
n

HEALTH STATUS

The outcomes of drug use

Beneficial

DRUG USE

Are the drugs effective in treating the disorder for which they
have been prescribed?
Can we establish risk estimates for the adverse effects associated
with their use?
Can we define sub-populations for which drugs are less
appropriate?

Provide the basis for decision-making at several levels of

health care: prescribing, drug formularies, and market
approval

BASIC APPROACH IN
PHARMACOEPIDEMIOLOGY

EXPOSURES

DETERMINANTS

OUTCOMES

DRUG USE

HEALTH STATUS

LARGE COMPUTERIZED DATABASE for

PHARMACOEPIDEMIOLOGY STUDY
n

Pharmacies, prescribers, commercial institution, health

insurance companies, and others started to collect and store
their health care data electronically

Research with these databases relatively inexpensive and

quickly

EXAMPLES OF LARGE
COMPUTERIZED DATABASE

MEASURING DISEASE
FREQUENCY
PREVALENCE
n

DEFINITION
n

The number of EXISTING cases of a disease in a defined

population at a given point in time or over a defined time period,
divided by the total population at a given point in time

For example:
n
n

Prevalence of dementia in X nursing home

Nursing home with 500 residents, the number of people with
dementia is 175
175/500 = 0.35 or 35%

Typically, the prevalence is a proportion

It can give us information about how common the disease is

MEASURING DISEASE
FREQUENCY
INCIDENCE
n

DEFINITION
n

The number of NEW cases of a disease that develop over a

defined time period in a DEFINED POPULATION AT RISK, divided
by the number of people in that POPULATION AT RISK in that
same time period

For example:
Tahun 2004, sebuah studi menginvestigasi frekuensi terjadinya
kanker serviks di suatu daerah terpencil di banjarbaru. Total 132
wanita berpartisipasi dalam studi ini. Hasil tes pap smear
mendeteksi 2 kasus kanker serviks. Studi ini melakukan follow up
kepada partisipan selama 1 tahun. Dalam periode ini, 1 orang baru
terdeteksi menderita kanker serviks.

MEASURING DRUG USE

n

The frequency of drug use can be calculated in a similar

manner to disease frequency

For example:
n

250 residents of 500 residents of nursing home use laxative for

more that 10 months per year

Prevalence?

For drug utilization between studies or between countries, a

classification system was needed

WHO (1990) developed a hierarchical drug coding system

the ATC classification system

ATC system (AnatomicalTherapeutic-Chemical)

STUDY DESIGN

STUDY DESIGN

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PHARMACOVIGILANCE
A BRIEF INTRODUCTION

PHARMACOVIGILANCE
DEFINITION
WHO:
n The

detection,
assessment, and
prevention of adverse
drug effects in human

Another definition:
n The

study of the safety

of marketed drugs
under the practical
condition of clinical
usage in large
communities

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Not all
hazard can
be known
before a
drug is
marketed

HISTORICAL EXAMPLES OF ADR

THALIDOMIDE tragedy (1961-1962)

n

Safe and effective hypnotic and antiemetic

Caused major birth defects (10000

children)

Phocomelia was a characteristic

feature

HISTORICAL EXAMPLES OF ADR

Sulfanilamide tragedy: Elixir sulfanilamide was an

improperly prepared sulfanilamide medicine that caused
mass poisoning in the United States in 1937. It caused the
deaths of more than 100 people.

Thalidomide disaster led to the establishment of the drug

regulatory mechanism

New drug shall be licensed by the well-established

regulatory authorities before being introduce into clinical
usage

PHARMACOVIGILANCE RATIONALE
CLINICAL DEVELOPMENT OF MEDICINES

LIMITATIONS OF PREMARKETING
CLINICAL TRIALS
n

Short Duration

Small Sample Size

Narrowly defined population

Narrow set of indications

Post Marketing Surveillance/Phase IV

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REACTIONS
TYPE A
n

Typically dose-related

Associated with the drugs pharmacological action

Common, predictable, and less serious than other types of

ADR

Example: Phenothiazine VS extra-pyramidal symptoms

+ DIAGNOSING ADVERSE DRUG

REACTIONS
TYPE B
n

From an allergy-type reaction to the drug

Usually very severe, often life threatening

Usually drug must be discontinued when such an ADR

happens

Example: anaphylactic shock after penicillin use

This type of event is rare, and it is usually not detected at the

phase of clinical trials

+ DIAGNOSING ADVERSE DRUG

REACTIONS
TYPE C
n

The most difficult to detect

Occur at random intervals or after a long induction time,

involve dose accumulation, and although relatively common
can be serious

Connection between the drug and the adverse event can be

difficult to prove

For example: breast cancer VS oral contraceptive

CURRENT METHODS OF
PHARMACOVIGILANCE
HYPOTHESIS-GENERATING
METHODS

HYPOTHESIS-TESTING
METHODS

HYPOTHESIS-GENERATING METHODS
SPONTANEOUS REPORTING SYSTEMS
n

To perform post-marketing surveillance of drugs

Mostly voluntary

Able to detect serious and unexpected drug reactions

Relatively inexpensive early warning systems

Weaknesses:
n
n

Under-reporting frequency of ADRs may be underestimated, the

delayed detection of ADRs, usually selective
Provide a numerator only, no information about the number of people
that have used a certain drug

UK: Yellow Card, the BNF, United States: the MedWatch form

YELLOW CARD

YELLOW CARD

The MedWatch

HYPOTHESIS-TESTING METHODS

RCTs

Cohort

Case-Control

PROSPECT?