CONCEPT OF RISK

IN
PHARMACOEPIDEMIOLOGY

Mrs. Rihana Begum P

Assistant Professor
Department of Pharmacy Practice
• Epidemiology determine the relationship
or association between a given exposure and
frequency of disease in population.

• Epidemiology does not determine the cause

of a disease in a given individual.
 CONCEPT OF RISK
• Risk is the likelihood or the probability of experiencing
some type of harm, or losing something that one values.
• Risk factors are variables or characteristics (biological -
genetic disorder/ageing, environmental-air/water pollution/
passive smoking or psychosocial- workload/deadlines)
associated with an individual that make it more likely that he
or she, as opposed to another person randomly selected from
the population, will develop a problem.
RISK FACTORS:
• Exists before a disorder or problem;
• Maybe time – limited or may continue over time;
• Can derive from the individual, the family, the community,
institutions or the general environment; and
• Can play a causal role or be a marker for a problem (BRAC)

CHARACTERISTICS OF RISKS:
1. Risk is not certain.
• Risk is based on probability. Therefore, not everyone who is
exposed to a risk condition or factor will have an adverse
outcome. Risk factors are “linked to” and “associated with”
negative outcomes.
• E.g. psychosocial outcomes v/s biological outcomes
• Teratogenic drug – thalidomide, environmental toxin – lead
2.Risk is a relative concept.
• Risk factors range from those that are only markers to
minimally harmful situations to those that are markers to life –
threatening situations.
• (Social continuum of risk/personal risk continuum)
• Risk is not a neutral concept. It involves determining what are
acceptable or unacceptable consequences.
• Risk factors work together over time to influence the
likelihood of a negative outcome.
• The longer the exposure to risk factors, the greater the
likelihood the health problem will occur.
• Risk Identification – Exist as a social context. The
identification of risk will be partially based upon their values,
biases, experience and knowledge.
 RELUCTANTLY
ASSUMED RISK

RISK PURSUED AS RISK FOR WHICH

OPPORTUNITY NO CHOICE

FREELYACCEPTED
RISK

Personal risk continuum.

Flow of Risk in Epidemiology:

TRUE RISK

PHARMACOEPIDEMIOLOGICAL STATISTICAL CONSIDERATIONS

CONSIDERATIONS (Sampling, models, etc)
(Bias, confounding etc)

MEASURED
ESTIMATED RISK
Risk in Pharmacoepidemiology:

• Health research involves the estimation of risk.

• In the case of drug related research, it is important to
understand the concept of risk.
• It is the probability of developing an outcome when exposed t
a drug.
• A drug is approved for human use only after measuring the
risks and benefits associated with it.
• HCP/Pharmacists should know the magnitude and frequency
of the risk involved in the drug in use.
• Each drug outcome has its own risk.
• It is a probability and depends on a variety of factors like age,
sex, physical conditions, food habits, other diseases, other
medicines, kinetics of drugs etc.
Measures of association:

• The key to epidemiological analysis is

comparison.

• Ameasure of association quantifies the

relation ship between the exposure and disease
among the comparison groups.

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 Measurement of risk
The risk of an ADR is expressed in many ways:
1. Attributable risk
2. Relative risk
3. Odds ratio
4. Time-risk relationship
 Attributable risk
• Useful approach to express the magnitude of
problems also called as the risk difference or
excess risk
• It is the difference between the risk in the
exposed group and the baseline risk in
unexposed population
• Thus, it is the risk in excess of the baseline risk
that may be attributed to exposure to the drug.
 Mostly calculated in Cohort Studies, where individuals
are assembled on exposure status and followed over a
period of time.
Investigators count the occurrence of the diseases.

The Cohort is then subdivided by the level of exposure

and the frequency of disease is compared between
subgroups.
Is a measure of the public health impact of a causative
factor.
 The calculation of this measure assumes that
occurrence of disease in the unexposed group
represent the baseline or expected risk for that
disease.
 It assumes that if the risk of disease in the exposed
group is higher than the risk in the unexposed group,
the difference can be attributed to the exposure.
The attributable proportion is the amount of the
disease in the exposed group attributable to the
exposure.

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 One is considered exposed and another unexposed.
AR = Rexposed - Rnon-exposed

where R is the rate of the outcome of the interest or the

Incidence.

Attributable Risk = Incidence in exposed – Incidence in unexposed

 Example
Astudy of smoking and lung cancer, the lung cancer
mortality rate among nonsmokers was 0.07 per 1,000
persons per year. The lung cancer mortality rate
among who smoked 1-14 cigarettes per day was 0.57
lung cancer deaths per 1,000 persons per year.
Calculate the attributable proportion?

40
Attributable proportion = (0.57 – 0.07) / 0.57X
100%= 87.7%

About 88% of the lung cancer among smokers of 1-14

cigarettes per day might be attributable to their
smoking.

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 RELATIVE RISK
Relative risk or risk ratio (RR) is the ratio of the probability of
an event occurring ( eg:developing of an ADR to a drug) in an
exposed group to the probability of the event occurring in non-
exposed group. (OR)
• Compares the risk of a health event among one group with the risk
among another group.

Includes 2 features:
i. A comparison of risk between two “exposure” puts
risks in context , and
ii. “exposure” is ensured by having proper denominators
for each group representing the exposure
Risk Ratio (RR)=

Risk of disease in group of primary interest

Risk of disease in comparison group

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Relative Risk Calculations
 RR = incidence in exposed
Incidence in non-exposed

It is a ratio of two risks, the risk of the outcome/event in the

treated group compared with the outcome in those not
exposed(control group).

RR = Proportion of events in experimental group/proportion o

events in control group.

RR above 1 indicates treatment/exposure is associated with t

outcome and below 1 means that the treatment is negatively
associated with the outcome.
 When the rate in the exposed group is equal to the rate in the
comparison group RR will be equal to 1.

An RR of 2 means that the rate in the exposed group is twice

that in the non-exposed group.

An RR of 0.5 means that the rate in the exposed

persons is half that of non-exposed persons.
 RR of more than
RR less than 1.0 RR of 1.0 1.0
Indicates a decrease Indicates identical
risk for the exposed
Indicates an
group. risk among the increase risk for
two groups. the group in the
Indicating that
perhaps exposure numerator
actually protects usually the
against disease exposed group.
occurrence.

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 Example

In outbreak of T.B among prison inmates in South

Carolina in 1999, 28 of 157 inmates residing on the
east wing of the dormitory developed T.B, compared
with 4 of 137 inmates residing on the west wing.

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 I

Risk of T.B among East Wing residents= 28/157 X100= 17.8%

Risk of T.B among West Wing residents=4/137X100= 2.9%

RR= 17.8/2.9= 6.1

The inmates who resided in the East wing of the dormitory were 6.1 times as likely to
develop T.B as those who resided in the West wing. 15
 Example

In an outbreak of varicella in Oregon in 2002,

varicella was diagnosed in 18 of 152 vaccinated
children compared with 3 of 7 unvaccinated
children. Calculate the risk ratio..?

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 Varicella + Varicella - Total
Vaccinated 18 134 152
Unvaccinated 3 4 7
Total 21 138 159

Risk of varicella among vaccinated children= 18/152 X100=11.8%

Risk of varicella among unvaccinated children= 3/7X100= 42.9%
RR=11.8/42.9=0.28

The vaccinated children were only approximately as one fourth to develop varicella
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as were unvaccinated children.
• Relative risk and odds ratio are important as measures of the
strength of association
– Important for deriving causal inference.

• Attributable risk is a measure of how much disease risk is attributed

to a certain exposure
– Useful in determining how much disease can be prevented.

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Relative risk is valuable in etiologic studies of disease.

Attributable risk is useful for Public Health guidelines and

planning.

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ODDS RATIO
• Is another measure of association that
quantifies the relation ship between an exposure
with two categories and health problem.
• In a case-control study the RR is called an
odds ratio (OR).
In statistics, an odds of an event is the ratio of:
the probability that the event WILL occur to
the probability that the event will NOT occur
In simpler term, an odds of an event can be
calculated as:

Number of events divided by number of non-events

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ODDS RATIO IN COHORT STUDIES:
ODDS RATIO IN CASE-CONTROL STUDIES:
 Example

Disease+ Disease- Total

Exposed 100 1900 2000
Not Exposed 80 7920 8000
Total 180 9820 10000

OD= 100X7920 / 1900X80 = 5.2

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 Example
A case control study was conducted in Hamad
Hospital to compare 35 lung cancer cases to controls
to determine the associated factors related to lung
cancer. Out of 117 subjects in the sample, 88 were
daily smokers. Only two cases were found to be
nonsmokers.

Calculate the Odds Ratio and interpret it. ?

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 Cases Controls Total
Lung Cancer Without Lung Cancer

Daily Smokers 33 55 88
Nonsmokers 2 27 29
Total 35 82 117

Odds Ratio = 33X 27 / 2X55 = 8.1

Daily Smokers showed risk of having lung cancer 8.1 times that of
nonsmokers.

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TIME RISK RELATIONSHIP:

• The outcome of an exposure to a drug is related to

the time.
• It is also true with risks associated with medicines.
• There is always a time related association of risk in
pharmacoepidemiology.
• Certain events like anaphylactic reactions happen
immediately after taking an injection while certain
other risk events occur after days or months or
even years.
.
 • Eg: prazosin , an alpha blocker has main effect in dilation of
veins and arteries which leads to reduction in BP. It is
sometimes also used for BPH. To minimize the impact of first
dose effect, prazosin is normally taken at bedtime. Other
drugs of same family, doxazosin and terazosin, can also
cause this phenomenon, though less frequently

• Delayed reactions to medications commonly begin more than

6 hrs after exposure but sometimes occur days after exposure.

Eg: delayed ADR to amoxicillin classically start between 7 to 10

days of exposure and may even begin 1 to 3 days after the
patients had stopped taking the medicine.
• Medications that cause delayed reactions include heparin, quinine,
sulphonamides, vancomycin, gold compounds, beta lactam antibiotics
and NSAIDs.
• Lomustine is an anticancer drug used in different types of cancer which
has an adverse effect of producing leucopenia that occurs 6 weeks after the
dose.

• The above mentioned aspects of medicine demonstrate that the exposure

time must always be considered and the risk should be expressed as a
function of time wherever possible in pharmacoepidemiology.