Measures of Association

Berhe Beyene(Email: berhebeyene2005@gmail.com)

Berhe Beyene
 Measure of association(1)
 The occurrence of disease in a group of people exposed to a risk
factor is compared to that observed in an unexposed
group in order to establish causal relationships, and to
identify effective interventions

 The most outstanding contribution of epidemiology is the study

of association and causation in health and disease

 This is also difficult, since it is often not easy to tell whether an

observed association between a condition and a risk factor
represents a cause-and-effect relationship

Berhe Beyene
 Measure of association(2)
Reasons for establishing or excluding causality
 To understand the determinant factors of disease
occurrence, distribution and outcome

 To identify the links in the chain of causality that are

amenable to intervention through general or specific
intervention program and

 To relate the output and impact of intervention

program to their input, i.e. a causal evaluation
Berhe Beyene
 Measure of association(3)
Definition of Association
An association is said to exist between two variables
when a change in one variable parallels or coincides
with a change in another variable

It is also called ‘co-variation’ or ‘correlation’

An association or co-variation may be positive or
negative
An association is a “Statistical relationship between
two or more events, characteristics, or other variables

Berhe Beyene
 Measure of association(4)
Statistical relationship between exposure and
disease
 Association is not causation!

 An association is said to be causal when it is

proved a change in independent (exposure)
variable produces a change in the dependent
(outcome) variable

Berhe Beyene
 Measure of association(5)
Strength of the Association
Cause/Risk factor/exposure Effect/Disease/Outcome

“Is there a relationship between the exposure

and outcome of interest? ”

“How strong is the relationship between a study

factor and an outcome?”

Berhe Beyene
 Measure of association(6)
Variables can be related or unrelated to one
another

 If they have relation, it can be: positively or

negatively, strongly or weakly (one variable can
have large or small effect on the other)
significantly or not significantly related

Berhe Beyene
 Measure of association(7)
Variables may have statistically significant
association.
Statistically significant association is that the
association is not likely due to chance
It is dependent on the strength of the
association and sample size

Berhe Beyene
 Measure of association(8)
 The key to epidemiologic analysis is comparison group.

 Measures of association summarizes the frequency

measures of two variables into a single summary
parameter that estimates the degree of association.

 Requires comparing two groups:

-Exposed Vs Unexposed
- Cases Vs non cases/controls

Berhe Beyene
 Measure of association(9)
 Commonly, the strength of the association is measured by the
Relative risk (RR) Odds Ratio (OR), attributable risk (AR), population
attributable risk (PAR) and its percents

 Epidemiologic data are often presented in the form of a

two-by-two table or contingency table

 two-by-two tables used to summarize frequencies of

disease and exposure and used for calculation of association

 Generally we can have r-by-c table

Berhe Beyene
 Measure of association(10)
Disease status total
Exposure Yes No

Yes a b a+b
No c d c+d
Total a+b b+d a+b+c+d
a+c – total number with disease
b+d - total number with no disease
a+b – total number exposed
c+d - total number unexposed
a+b+c+d – grand total/total population
Berhe Beyene
 Measure of association(11)
RELATIVE RISK [RR]
 Risk: The probability of an event occurring overtime
 Risk Ratio: The ratio of the risk of disease incidence in
exposed group compared to the risk in those unexposed
 Often, a measure of association between incidence of
disease and exposure of interest
 RR estimates the magnitude (size) of an association
between exposure and disease.
 It indicates the chance of developing the disease in the
exposed group relative to the non exposed group for a
factor
Berhe Beyene
 Measure of association(12)
RR= incidence of a disease among exposed group (Ie)
incidence of disease among non-exposed group (Io)
RR= IE/IO or CIE/CIO Exposure Disease Total
status status
Yes No

Yes (+) a b a+b

No (-) c d c+d
Total a+b b+d a+b+c+d

This is usually used in cohort and experimental studies

Berhe Beyene
 Measure of association(13)
Example of cohort study
Table 1: data from a cohort study of oral
contraceptive (OC) use and bacteriuria among
women aged 15-49 years
Current OC Bacteriuria total
use
Yes No
Yes 27 455 482
No 77 183 260
Total 104 638 742
Berhe Beyene
 Measure of association(14)
Calculate RR?

RR = Ie/Io or
RR = a/a+b
c/c+d

= (27/482)x1000 = 1.4
(77/1908)x1000
 Interpretation: women who used oral contraceptive had 1.4
times higher risk of developing bacteriuria when compared
to non-users.
Berhe Beyene
 Measure of association(15)
Example 2:
Given:
 Crude incidence rate of exposed group
population = 72 per 10,000 Person year and
 Crude incidence rate Non-exposed group Popn = 58 per
10,000 Person year

Calculate RR=?

Interpretation: The exposed group are 1.24 times more likely

to develop the disease than are the non-exposed group.

Berhe Beyene
 Measure of association(16)
More Examples
Incidence per
Have CHD Free of CHD 1000/ year

Smokers 84 2916 3000

Non-smokers 87 4913 5000
Total 171 7829 8000

Incidence in smokers = ?
Incidence in non-smokers = ?
Relative risk = ?
Berhe Beyene
 Measure of association(17)
 Interpretation: The disease is RR times more likely to occur among
the exposed to the suspected risk factor compared to those with no
such exposure.
 The larger the value of RR, the stronger the association.

 RR > 1, DIRECT relationship between exposure and outcome

(positive association) - indicates increased risk

 RR < 1 indicate a negative association between the risk factor

and the disease.(i.e. protective)- decrease risk

 RR = 1, NO relationship between exposure & outcome

- disease incidence rates are identical between groups

Berhe Beyene
 Measure of association(18)
Guideline for strength of association
RR= 1.0, No association
RR= 1.1-1.3, Weak association
RR= 1.4-1.7, Mild association
RR= 1.8-3.0 Moderate and
RR= 3.0-8.0 Strong association

The further RR away from 1, the stronger the association

between exposure and disease

For inverse associations (incidence rate is less than 1.0), take

the reciprocal and look in above table, e.g., reciprocal of 0.5 is
2.0, which corresponds to a “moderate” association.

Berhe Beyene
 Measure of association(19)
Odds Ratio (OR)
Odds: The probability of an event's occurring to the
probability of its not occurring

Odds Ratio: The ratio of two odds or the ratio of the

odds of exposure in cases compared with the odds of
the exposure in controls

Berhe Beyene
 Measure of association(20)
 The idea behind odds ratio is that if a disease is casually
related with the factor, then the odds of exposure in the
diseased group will be higher compared to the
corresponding odds in the non-diseased group

 Usually applied to cross sectional and case-control

studies but not for incidence studies

 It is an indirect measure of a risk in a disease of rare

disease occurrence

Berhe Beyene
 Measure of association(21)

 Indicates the likelihood of having been exposed among

cases relative to controls

Odds = the chances of something happening

the chances of it not happening

 Let p = the probability of an event

1-p = the probability that the event does not occur
 Odds of the event = p/1-p
OR = Odds of exposure among cases
Odds of exposure among controls

Berhe Beyene
 Measure of association(22)
Exposure Cases Controls
Exposed a b a+b
Not exposed c d c+d
Total a+b b+d a+b+c+d

a = number of persons exposed and with disease

b = number of persons exposed but without disease
c = number of persons unexposed but with disease
d = number of persons unexposed and without disease
a+c = total number of persons with disease (cases/patients)
b+d = total number of persons without disease (controls)
a+c +b+d = grand total
Berhe Beyene
 Measure of association(23)
Then we calculate odds of exposure among cases to that of among controls.

The odds of exposure among cases

= Exposed cases = a/c
Non exposed cases
The odds of exposure among controls
= controls exposed = b/d
Controls not exposed

Odds ratio (OR) is the ratio of the two odds comparing the cases to the
controls:

Berhe Beyene
 Measure of association(24)
E.g1: Data from a case-control study of current oral
contraceptive(OC) use and MI in pre-menopausal
female nurses

Calculate OR=?
Berhe Beyene
 Measure of association(25)
OR =ad/bc= 23x2816 /304x133=1.6

Interpretation: the odds of having MI is 1.6 times higher among

OCP users compared to that of the non OCP users.
Interpretation of OR
 Odds ratio = 1: the odds of disease in the exposed and non
exposed is the same, No association
 Odds ratio > 1: the odds of disease is greater in the exposed ,i.e.
the factor may be a risk factor

 Odds ratio < 1: the odds disease in the exposed is less than the
odds of disease in the non exposed i.e. the factor may be a
protective
Berhe Beyene
 Measure of association(26)

It is used for a rare disease when a and c are very much less
than b and d, respectively i.e. a <<< b, so, a+b ≈ b
c <<< d, so, c+d ≈ d

Berhe Beyene
 Measure of association(27)
Example of Rare Disease
Exposure D+ D- Total
E+ 90 499,950 500,040
E- 10 499,950 499,960
Total a+b b+d a+b+c+d

RR= (90/500040)/ (10/499960) = 9.0

OR=ad/bc= (90x499950)/(499950x10)=9.0
 So OR nearer to Risk Ratio when disease is rare

Berhe Beyene
 Measure of association(28)

Attributable Risk(AR): it is also known as risk difference or

excess risk among exposed groups
The number of cases among the exposed that could be
eliminated if the exposure were removed

 AR = Incidence in exposed - Incidence in unexposed

= a/( a + b) – c/( c+ d)
What is the excess risk among exposed individuals?
 AR quantifies the excess risk in the exposed that can be
attributable to the exposure.
 Indicates the number of cases of the disease among the
exposed that can be attributed to the exposure itself.

Berhe Beyene
 Measure of association(29)

Concept of Attributable risk

 Incidence in the exposed group = incidence not due
to the exposure (background exposure) + incidence
due to the exposure

 Incidence in the non exposed group = incidence not

due to the exposure (background exposure)

Berhe Beyene
Measure of association(30)
Attributable Risk

I= Incidence
Berhe Beyene
 Measure of association(31)
How to Calculate AR ?
 Attributable risk is defined as the difference between the
incidence rates (or cumulative incidence) in the exposed and
non-exposed.
For example, in a cohort study :AR = Ie – Io or AR = CIe – CIo
where Ie = incidence rate in the exposed
Io = incidence rate in the non-exposed

(i)for Static populations: Attributable Risk = CIe – CIo

(ii) for Dynamic populations
Attributable Risk = Ie - Io py
Or it can be generated from RR; AR= (CIo) x (RR-1)

Berhe Beyene
 Measure of association(32)
Assumptions:
 Interpretation of the AR is dependent on the assumption that a
cause-effect relationship exists between exposure and disease.
 If no association between the exposure and disease,Ie – Io= 0 so AR =
0.

Interpretation
 If there is an association between exposure and disease and
AR > 0, the AR is the number of cases of the disease among the
exposed that could be eliminated if the exposure was
eliminated. Thus, the AR is useful as a measure of public health
impact of an exposure.

Berhe Beyene
 Measure of association(33)
Uses of attributable risk estimates
 Are a measure of the absolute effect of the
exposure.
 Are thus a measure of the public health
impact of the exposure.
 Can be calculated in static and dynamic
populations

Berhe Beyene
 Measure of association(34)
Eg 1. Fast driving and Automobile Deaths
Dead Not Dead Risk AR
Fast 100 1900 2000 0.04
Slow 80 7920 8000
Total 180 9820 10000

Ie =100/2000 = 0.05
Io = 80/8000 = 0.01
AR = 0.05-0.01 = 0.04

Berhe Beyene
 Measure of association(35)
• Eg.2: OC use and Bacteriuria

• Interpretation: the excess occurrence of bacteriuria

among OC users attributable to their OC use is 156.6 per
10,000
Berhe Beyene
 Measure of association(36)
Attributable Risk Percent (AR%)
 Attributable proportion, etiologic Fraction
 What proportion of cases is attributed to the actual exposure
among exposed people?
 Allows us to calculate the proportion of the disease among the
exposed that is attributable to the exposure.

 It is an estimate of the proportion of the disease in the exposed

group that could be prevented by eliminating the exposure.
How to Calculate?
AR% = (Ie – Io)/ Ie *100 or AR% = (RR-1)/RR*100 , where RR is
the risk ratio or relative risk of the exposure and disease (cohort
study)
Berhe Beyene
 Measure of association(37)
Recall OC use and bacteriuria example above:
CIe = 27/482 = .0560
CIo = 77/1908 = .0404
AR% = (CIe – CIo)/C Ie*100
= (.05601-.04036)/.05601*100 = 27.96%

Interpretation: If OC use does cause bacteriuria, about

28% of bacteriuria among women who use OCs can be
attributed to their OC use.

Berhe Beyene
 Measure of association(38)
Preventive Fraction
 Exposures associated negatively with outcome variable have
a relative risk below the unity or 1.
 If relative risk is < 1, the exposure is protective
When exposure is preventive (AR is less than 0) then the
analogous figure to the AR is;

PF% = Io - Ie x 100%
Io

Berhe Beyene
 Measure of association(39)
Vaccine efficacy
Vaccine Population Cases Cases/populati RR
on
Vaccinated 301,545 150 0.49 0.28
Unvaccinated
298,655 515 1.72

Total 600,200 665 1.11

PF= Iunexposed-Iexposed PF=(1.72-0.49)/1.72 =72%

Iunexposed 1.72
or PF=1-RR= 1-0.28= 72%
Interpretation : The vaccine has about 72% protective effect
Berhe Beyene
 Measure of association(40)
Population Attributable Risk (PAR)
 Excess risk of disease in total population attributable to
exposure
 What is the excess risk among the general population that is due to exposure
of interest?
 The AR quantifies the excess risk in the “exposed” group.
 The PAR estimates the excess rate of disease in the “total”
study population of exposed and non-exposed that is
attributable to the exposure.

Uses of PAR
 The PAR helps determine which exposures have the most
relevance to the public’s health.
 Can help guide the allocation of resources aimed at
interventions
Berhe Beyene
 Measure of association(41)
How to Calculate?
PAR = It – Io or
PAR = CIt – CIo
where It= incidence rate in the total population
Io =incidence rate in the non exposed
Alternatively, the PAR can be calculated as:
PAR = (AR)*Pe
where AR is the attributable risk and Pe is the proportion of
exposed people in the population

Berhe Beyene
 Measure of association(42)
Population Attributable Risk

Berhe Beyene
 Measure of association(43)
POPULATION ATTRIBUTABLE RISK FRACTION [PAR%]
 What proportion of cases is attributed to the actual exposure
among the general population?
 Estimate the proportion of disease in the study population that is
attributable to the exposure and thus could be eliminated if the
exposure were eliminated.
 expressed as a percentage of total risk in population

 PAR% = Ipopulation - Iunexposed x100

Ipopulation
Measures public health impact of an exposure
 Similar to the AR%, the PAR% is the “proportion” of disease in
the study population that is attributable to the exposure and
could be eliminated if the exposure was eliminated
Berhe Beyene
Measure of association(44)

Berhe Beyene
 Measure of association(45)
In general
1. No association between exposure and outcome
RR/OR= 1 there is no association
AR = 0
2. Positive association between the exposure and the disease
(i.e., more exposure, more disease)
RR/OR > 1, the exposure is risk
AR > 0

3. Negative association between the exposure & the disease

(i.e., more exposure, less disease, the exposure is
preventive)
RR/OR < 1 (but not negative)
AR< 0 (negative )
Berhe Beyene
 Measure of association(46)
4. If confidence interval of RR/OR includes the unity (1),then there
is no significant association

5. If the RR/ OR is far from the unity (1), it is a sign of presence of

significant association

6. AR/ PAR > 0, the exposure is attributing

7. AR/ PAR = 0, there is no attribution

8. AR/ PAR < 0, the exposure is not attributing (it is

preventive)
Berhe Beyene
?
Berhe Beyene