Measures of Association

and
Public Health Impact
Ephrem , BSC, MPH, PhD fellow
 Learning Objectives

 List common measures of association and

measures of public health impact

 Calculate and interpret risk ratio and odds

ratio and describe their use

 Calculate and interpret attributable risk

percent and vaccine efficacy and describe
their use
n
"Every epidemiologic study
can be summarized
in a 2-by-2 table."

n
 Standard Two-by-Two Table

Outcome

Ill (D+) Well (D) Total Risk

Exposed (E+) a b a+b a/a+

b

Unexposed c d c+d c/c+

(E–) d

Total a +c b+d a+b+c+d

a + b =total no of individual who are exposed.

C + d= total no of individual who are not

exposed

a + c= total no of individual with disease.

b + d = total no of individual with out disease.

a+b+c+d= total sample size of the study.

Biological Weapons Measures of Association and
Proliferation Prevention Public Health Impact 5
 How to do a 2x2 table

 We are able to make several 2X2 tables

 We should take one category as a referent
Lung CA
1
Yes No
Lung CA
1- 7 cigarettes 35 1,560
Yes No
Never smock 25 3,456
Never smock 25 3,456
1- 7 cigarettes 35 1,560 2 Lung CA
8+ cigarettes 58 890 Yes No
8+ cigarettes 58 890
Never smock 25 3,456
n
 Association —
Definition
 Statistical relationship between two or more
variables

n
 Measure of Association
 Epidemiologic Measure of Association

 Types of measures:
 Relative difference: risk ratio, rate ratio, odds ratio
Quantifies or expresses the strength of the
relationship between an "exposure" and “outcome”
of interest

 Absolute difference: risk difference Quantifies the

difference in occurrence of disease or death
between two groups of people who differ on
"exposure“

n
 “Exposure”
 Exposure in usual sense
 e.g., ingestion of contaminated food
 e.g., droplets from someone with active
pulmonary tuberculosis
 Behaviors
 e.g., sharing needles, drinking alcohol etc

 Treatment
 e.g., intervention - education program

 Trait
 e.g., genotype
n
 Disease “Outcome”
 e.g., malaria, TB
 e.g., diabetes

 Event
 e.g., injury from land mine,
car accident

 Condition
 e.g., blindness

 Death
 Other
n
 Measures of Association

Exposure Outcome

Is there a relationship between the

exposure and outcome of interest?
 Description of Relationships
 Variables can be related or unrelated to one
another

 If related, variables can be

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

n
 Relationships between variables —
Related or unrelated?

10

Dependent variable
6

0.00 20.00 40.00 60.00

Independent Variable

Related unrelated
 Relationships between variables —
Positive and negative association?

10 10

Y Y

0 0

0 X 1 0 X 1

Positive Negative
n
 Relationships between variables —
Large or small effect?

10 10

Y Y

0 0

0 X 1 0 X 1

Large Small

n
 Relationships between variables —
Statistically Significant or Not?

 Statistically significant
 association is unlikely to be due to
chance

But remember:
 Statistically significant means that the
association is not likely due to chance

 It is dependent on the strength of the

association and sample size
n
 Interpretation
RR/ OR
1. RR/ OR > 1, the exposure is risk

2. RR/ OR = 1, there is no association

3. RR/ OR < 1, the exposure is Preventive

4. If confidence intervals of RR/ OR touch 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
 Relative risk or risk ratio
 It compares the risk of a health-related
events (disease) in two groups.

 It directly compares new occurrence

(incidence) disease among exposed and non-
exposed

 It estimates the likelihood of developing

disease in exposed relative to non-exposed.
 Relative Risk
incidence of a disease among exposed (a/(a+b)) Re
RR = incidence of a disease among non-exposed (c/(c+d)) R è
Disease
Yes (+) No (-) K
RR = Re / Rè Exposure a b a+b n
Yes (+)
. a . c d o
c+d
RR =
No (-)
. a+b .
w
. c .
n
c +d

 It is a direct measurement of a risk

 It is usually used in Cohort and Experimental study

design
 Cont…

CA + -

Smoker 112 176 288

nonsmoker 88 224 312

total 200 400 600
find RR=?
so/n RR= risk in exposed/risk in non exposed

Biological Weapons Measures of Association and

Proliferation Prevention Public Health Impact 20
Scenario 1:
The study is single center, double blind, cluster randomized,
placebo controlled trial. determine the effectiveness of
chemoprophylaxis using a single dose of rifampicin to prevent
leprosy in close contacts. 18 869 of the 21 711 contacts (86.9%)
were followed-up at four years. Ninety one of 9452 contacts in
the placebo group and 59 of 9417 in the rifampicin group had
developed leprosy.

n
 This indicates that the exposed group to
smoking is 1.38 times likelihood to develop
the disease (Ca) as compared with non
exposed group to smoking.

 Or the exposed group to smoking is higher

risk 138% than the non exposed group of
developing Ca.

Biological Weapons Measures of Association and

Proliferation Prevention Public Health Impact 22
 Follow-up Study
 Originalenrollment 1971 - 1975
 Follow-up 1982 – 1984

 Complete follow-up on:

- Enrolled Alive (Follow
Up)
 Male diabetics 189 89
 Male non-diabetics 3151 2340
 Total 3340 2429

who were ages 40-77 years at enrollment

Biological Weapons Measures of Association and

Proliferation Prevention n Public Health Impact 23
 Risk Calculation
Example
1. Deaths in diabetic men
100 deaths
189 men at start of follow-up period
Risk = 100/189 = 0.529 = 52.9%

2. Deaths in non-diabetic men

811 deaths
3151 men at start of follow-up period
Risk = 811/3151 = 0.257 = 25.7%
Biological Weapons Measures of Association and
Proliferation Prevention Public Health Impact 24
 Risk Ratio / Relative Risk

Risk in "exposed" group

Risk in "unexposed" group

EXAMPLE 1:
Relative risk of death among diabetic men vs.
non-diabetic men

RR = 100/189 = 0.529 = 52.9% = 2.1

811/3151 0.257 25.7%
 Sample Cohort Study
 Women of childbearing age, in country XX
 Followed for almost 3 years

- Enrolled TB
Incidence
 HIV-positive 249 22
 HIV-negative 310 1
 Total 559 23

Biological Weapons Measures of Association and

Proliferation Prevention n Public Health Impact 26
 Comments about Risk Ratio

• The further away from 1, the stronger

the association between exposure and
disease

• Can only calculate Risk Ratio from

cohort study and experimental studies
 Odds ratio, cross product ratio

 Itis usually used in a case-control and

cross-sectional analytic study designs

 Cases and controls are predetermined

and we are calculating to determine
whether cases or controls are more
exposed to a postulated risk factor.
 Odds ratio
OR = . Odds of exposed among cases (a/c)
Oe .
Odds of exposed among controls (b/d)
Oè

Disease
OR = Oe /Oè Yes (+) No (-)
OR = . a/c . Exposure
a b
b/d Yes (+)

No (-)
c d
ad/bc
a+c b+d
KNOWN
 Odds Ratio as Cross-Product Ratio
Assuming it is a
case control study
Dead Alive
Diabetic 100 89
Nondiabetic 811 2340

OR = ad / bc

OR = ad = 100 x 2340 = ???

bc 89 x 811
 Odds Ratio

 Can be calculated from case-control and

cross-sectional study
 Exercise one

From 2000 – 2005 a research group enrolled 2000 pregnant

women in an epidemiological study to investigate the effect of
anemia in delivery outcome. Among the 650 women who had
anemia, 140 experience a preterm delivery or low birth weight of
their baby. Among the 1350 women who had no anemia, 40
experienced a preterm delivery or low birth weight of their babies.

1. Identify the study design

2. Label two by two table

3. Calculate the appropriate measures of association and give

interpretation
Exercise Two

One study was conducted in Addis Ababa to investigate

the relationship between alcohol consumption and chronic
liver disease (cirrhosis). 300 patients with confirmed
chronic liver disease (cirrhosis) were compared with 360
patients admitted to hospital with other disease. Heavy
drinking was reported by 133 of the 300 cirrhosis patents
and 94 of the 360 comparative groups.
1. Identify the study design
2. Label two by two table

3. Calculate the appropriate measures of association and give

interpretation
Attributable risk
(AR)

n
 Definition
Relative Risk
A measure of the strength of association
based on prospective studies.

Attributable Risk

The amount of disease that can be attributed

to a certain exposure.

n
 Measures of Public Health Impact
 Places exposure – disease associations from public
health perspective

 Quantifies expected reduction in disease occurrence

if harmful exposure could be eliminated

 It is calculated as risk difference (RD)

Risk Difference = Risk exposed - Risk non-exposed

n
 Risk Difference

 Relative Risk: (Multiplicative)

RR = Ie / Io
(strength, cause ?)

 Attributable Risk: (Additive)

AR=Ie-Io
(impact).

n
 Attributable Risk

Incidence
Incidence

I exposed – I unexposed

Exposed Unexposed
exposed unexposed

I = Incidence
n
 Attributable Risk Percent (AR%)

 AR% is an attributable risk expressed as a

percentage of risk in exposed

 What is the proportion of disease among the

exposed which …
 can be attributed to the exposure

 Synonyms
 Attributable proportion

 Attributable fraction

 Etiologic fraction (EF)

 Attributable Risk Percent (AR%)

Incidence

Iexposed - Iunexposed RR - 1
%  x 100
Iexposed RR

Exposed Unexposed

Biological Weapons Measures of Association and

Proliferation Prevention Public Health Impact 40
 Attributable Risk Percent

AR% = Risk in group 1 - Risk in group 2

Risk in group 1

EXAMPLE:
Attributable risk percent for deaths among
diabetic men vs. non-diabetic men
(0.529 - 0.257)/0.529 = 0.272/0.529 = 51.4%

"About half of the deaths among diabetic men

may be attributed to their diabetes."

n
 AR & AR% in Case-Control
Studies
 No direct estimate of risk

 No risk estimates in case-control study

 Attributable risk (risk difference)

 and AR percent

 If odds ratio approximates relative risk (rare

occurrence), it is possible

OR - 1
AR% = X 100
OR
 Exercise

Annual mortality rate per 100, 000

person year

Lung cancer Heart disease

Cigarette smoking 160 1000

Non smoker 10 500

1. Smoking is likely to cause which of the disease? Why?

2. If the government successfully campaign for elimination of
smoking from which disease are more people saved? Why?
Prevented fraction
 Prevented Fraction (PF)
For exposures associated negatively with outcome
variable have a relative risk below the unity (1).

 If relative risk is < 1, the exposure is a protective

 Proportion of potential cases

 which could have occurred if the exposure had

been absent

 prevented by the exposure

 Prevented fraction
I unexposed – I exposed
PF =
I unexposed
= 1 - RR

Unexposed exposed
 PF: Vaccine efficacy
Pop. Cases Cases/1000 RR

Vaccinated 301,545 150 0.49 0.28

Unvaccinated 298,655 515 1.72 Ref.

Total 600,200 665 1.11

PF = I unexposed – I exposed
PF = =
I unexposed
= = 0.72
 Pfizer-BioNTech and Moderna COVID-19 vaccines have
been shown to be effective in preventing symptomatic
COVID-19 in randomized placebo-controlled Phase III
trials. Among 3,950 participants with no previous
laboratory documentation of SARS-CoV-2 infection, 2,479
(62.8%) received both recommended mRNA doses and
477 (12.1%) received only one dose of mRNA
vaccine. Among unvaccinated participants, 1.38 SARS-
CoV-2 infections were confirmed by (RT-PCR) per 1,000
person-days. In contrast, among fully immunized (≥14
days after second dose) persons, 0.04 infections per 1,000
person-days were reported.

Biological Weapons Measures of Association and

Proliferation Prevention n Public Health Impact 48
 Pop. Cases Cases/1000 RR
Vaccinated 301,545 150 0.49 0.28
Unvaccinated 298,655 515 1.72 Ref.
Total 600,200 665 1.11

Expected number of cases among vaccinated if

unvaccinated
301,545 x 1.72 = 519
1,000

Observed number of cases 150

Estimated number of cases prevented = 369/ 519

= 72% .
Population Attributable
Risk
 Population attributable risk

 We want to study health related problem in a

community
 But we do the study in a sample of a population
 We also conclude our result to the population
where the sample come from.

 When we discuss about population attributable

risk, we are trying to generalize what we found
in our sample
Population Attributable Risk (PAR)

 Excess risk of disease in total population

attributable to exposure

 Reduction in risk achieved if population was

entirely unexposed

 Helps determining exposures relevant to public

health in community
 Population Attributable Risk

Risk

I population – I unexposed

Population Unexposed
 Population Attributable Risk Percent (PAR%)
(Population Attributable Fraction)

 Proportion of cases in the population attributable

to the exposure

 PAR expressed as a percentage of total risk in

population

I population – I unexposed
PAR% = X 100
I population
 Summary
 RR/ OR  Association

 AR (AR%)  Impact on sample

 PAR (PAR%)  Impact on population

 Interpretation
RR/ OR

No association

Preventive Risk

0 1
 Interpretation

RR/ OR

1. RR/ OR > 1, the exposure is risk

2. RR/ OR = 1, there is no association

3. RR/ OR < 1, the exposure is Preventive

4. If confidence intervals of RR/ OR touch 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
 Interpretation
AR

No association

Preventive Risk

0 0
 Interpretation
AR/ PAR

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

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

3. AR/ PAR < 0, the exposure is not attributing

 Summary
 Among exposed
 Attributable risk

 Attributable risk percent

 Prevented fraction

 In the population
 Population Attributable Risk

 Population Attributable Risk percent