All information regarding measures of risk in simple, understanding way

1. CONCEPT OF RISK IN
PHARMACOEPIDEMIOLOGY
Dr. Yuva Sri Sai Anumula
Assistant Professor
Department of pharmacy practice

2. • 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.

3. • 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.
CONCEPT OF RISK

4. 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

5. 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.

6. RELUCTANTLY
ASSUMED RISK
RISK PURSUED AS
OPPORTUNITY
RISK FOR WHICH
NO CHOICE
FREELYACCEPTED
RISK
Personal risk continuum.

7. Flow of Risk in Epidemiology:
TRUE RISK
PHARMACOEPIDEMIOLOGICAL
CONSIDERATIONS
STATISTICAL CONSIDERATIONS
(Sampling, models, etc)
(Bias, confounding etc)
MEASURED
ESTIMATED RISK

8. 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 to
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.

9. 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.
8

10. 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

11. 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.

12.  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.

13. The calculation of this measure assumes that
occurrence of disease in the unexposed group
represent the baseline or expected risk for that
disease.

14. 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.

15. The attributable proportion is the amount of the
disease in the exposed group attributable to the
exposure.
7

17.  One is considered exposed and another unexposed.
AR = R - Rexposed non-exposed
where R is the rate of the outcome of the interest or the
Incidence.
Attributable Risk = Incidence in exposed – Incidence in unexposed
%AR = 100 * R – Rexposed non-exposed
R
exposed

18. 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

19. 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.
41

20. RELATIVE RISK
 Relative risk or risk ratio (RR) is the ratio of the probability of
an event occurring ( eg:developing of anADR 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

21. Risk Ratio (RR)=
Risk of disease in group of primary interest
Risk of disease in comparison group
11

22. Relative Risk Calculations

23.  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 of
events in control group.
 RR above 1 indicates treatment/exposure is associated with th
outcome and below 1 means that the treatment is negatively
associated with the outcome.

24.  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.

25. RR of more than
RR of 1.0 1.0RR less than 1.0
Indicates a decrease
Indicates identical Indicates anrisk for the exposed
risk among the
two groups.
increase risk for
the group in the
numerator
group.
Indicating that
perhaps exposure
actually protects
against disease
occurrence.
usually the
exposed group.
12

26. 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.
14

27. T.B + T.B - Total
a=28 b=129 a + b=157East Wing
West Wing
Total
c= 4 d=133 c + d=137
a+c=32 b+d= 262 a+ b+ c+ d=294
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

28. 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..?
16

29. Varicella + Varicella - Total
152
7
Vaccinated
Unvaccinated
Total
18
3
134
4
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
17
as were unvaccinated children.

30. • 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.
42

31. Relative risk is valuable in etiologic studies of disease.
Attributable risk is useful for Public Health guidelines and
planning.
43

32. ODDS RATIO

33. • 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).

34. 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

35. In simpler term, an odds of an event can be
calculated as:
Number of events divided by number of non-events
23

36. 24
ODDS RATIO IN COHORT STUDIES:

37. 25
ODDS RATIO IN CASE-CONTROL STUDIES:

38. Example
Disease+ Disease-
1900
Total
2000
8000
10000
Exposed 100
Not Exposed 80
Total 180
7920
9820
OD= 100X7920 / 1900X80 = 5.2
26

39. 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. ?
28

40. Cases Controls Total
Lung Cancer Without Lung Cancer
Daily Smokers
Nonsmokers
Total
33
2
55
27
82
88
29
35 117
Odds Ratio = 33X 27 / 2X55 = 8.1
Daily Smokers showed risk of having lung cancer 8.1 times that of
nonsmokers.
29

41. 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.
.

42. • 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.

43. • 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.