Measures of Association

Prof. Dr. Bhisma Murti, MPH, MSc, PhD

Overview for Today

Purpose of measuring associations
The 2x2 table
Ratio comparisons (relative measures)
Relative risk, risk/rate ratio, odds ratio

Difference comparison (absolute measures)

Risk/rate difference, population risk/rate difference, attributable
proportion among exposed and total pop.

Formula, examples, interpretations

Put it all together with an example

Why Estimate Comparisons?

Quantitative comparison is an essential element of
epidemiology to identify disease determinants.
Summarize relationship between exposure and disease
by comparing at least two frequencies in a single
summary estimate.
Overall rate of disease in an exposed group says nothing
about whether exposure is a risk factor for or causes a
disease.
This can only be evaluated by comparing disease occurrence in
an exposed group to another group that is usually not exposed.
The latter group is usually called the comparison or reference
group.

Two Main Options for Comparison

Calculate ratio of two measures of disease frequency
1.
2.
3.
4.

Relative comparison
Strength of relationship between exposure and outcome
Magnitude of association between exposure and outcome
How much more likely one group is to develop outcome

Calculate difference between two measures of disease

frequency
1. Absolute comparison (attributable)
2. Public health impact of exposure
3. How much greater is the frequency of outcome in one group

Comparing Ratios

The 2-by-2 Table

Outcome

Exposure

Yes

No

Total

Yes

a+b

No

c+d

a+c

b+d

a+b+c+d

Total

Prevalence or cumulative incidence

= a/(a+b) among exposed
= c/(c+d) among unexposed
= (a+c)/(a+b+c+d) among total population

Example #1
Data from a fixed cohort study of oral contraceptive use (OC)
and myocardial infarction (MI) in pre-menopausal women
followed for 5 years (adapted from Rosenberg et al AJE 1980).
MI
Yes

No

Total

Yes

23

304

327

No

133

2816

2949

Total

156

3120

3276

OC use

5-year CI of myocardial infarction

= 23/327 = 7.0% among OC users
= 133/2949 = 4.5% among non-OC users

The 2-by-2 Table for Person-Time Data

Outcome
Yes

No

Total

Yes

PTexp

No

PTunexp

a+c

Total PT

Exposure

Total

Incidence rates
= a/(PTexp) among exposed
= c/(PTunexp) among unexposed
= (a+c)/(Total PT) among total population

Example #2 -- Using Person-Time Data

Data from a dynamic cohort study of postmenopausal
hormone use (PH use) and coronary heart disease (CHD)
among women (Stampfer et al NEJM 1985)
CHD
Yes

No

Total

Yes

30

---

54,308 PY

No

60

---

51,477 PY

Total

90

---

105,786 PY

PH use

Incidence rate of CHD

= 30/54,306 PY = 55.2/100,000 PY among PH users
= 60/51,477 PY = 116.6/100,000 PY among non-PH users

Relative Comparisons
Based on ratio of 2 measures of frequency
Often referred to as relative risk
Dimensionless and ranges 0 - infinity
Prevalence ratio (PR)
= Pexp / Punexp = [a / (a+b)] / [c / (c+d)]
Cumulative incidence ratio (CIR)
= CIexp / CIunexp = [a / (a+b)] / [c / (c+d)]
Incidence rate ratio (IRR)
= IRexp / IRunexp = [a / PTexp] / [c / PTunexp ]

Interpretations of Risk Ratios

Gives information on the relative effect of the exposure
on the disease.
Tells you how many times higher or lower the disease
risk is among the exposed as compared to the
unexposed.
Therefore, commonly used in etiologic research as a
measure of risk
Note:
Some people consider CIR and IRR better measures of relative
risk than PR because CIR and IRR include measures of time

Example #1 (continued)
MI

OC use

Yes

No

Total

Yes

23

304

327

No

133

2816

2949

Total

156

3120

3276

5-yr CIR of MI among OC users compared to non OC users:

5-yr CIR= CIe/CIu = [a/(a+b)]/[c/(c+d)] = (23/327)/(133/2949) = 1.6
Interpreted as relative risk:
1. Women who used OCs had 1.6 times the risk of having MI over 5
years compared to non-OC users (1.6-fold increased risk).
2. There is a 60% increase risk of MI among OC users over a 5-yr period
compared to non-users (60% more likely to have MI).

Example #2 (continued)
CHD

PH use

Yes

No

Total

Yes

30

---

54,308 PY

No

60

---

51,477 PY

Total

90

---

105,786 PY

Incidence rate ratio of CHD among PH users compared to non-PH users:

IRR = IRe/IRu = [a/PTe]/[c/PTu] = 0.5
Interpreted as a relative risk:

Women who used PH had 0.5 times, or half, the risk of developing
CHD compared to non-users.

Interpretation of Relative Risk

RR=1
Risk in exposed = risk in non-exposed
No association

RR>1
Risk in exposed > risk in non-exposed
Positive association, factor is associated with disease
Larger RR stronger association

RR<1
Risk in exposed < risk in non-exposed
Negative association, factor is protective

RR for exposed = 1/RR for non-exposed

Need to pay attention to referent group
Risk for whom compared to whom?

Example #1: Extension to 2 x 2 Table

MI

OC use

Yes

No

Total

< 1 year

31

35

1-4 years

107

112

5-9 years

127

134

10+ years

39

46

Never

133

2816

2949

Total

156

3120

3276

Any Two Groups Can Be Compared

Applying Formulas on Appropriate Cells
Yes

No

Total

< 1 year

31

35

1-4 years

107

112

5-9 years

127

134

10+ years

39

46

Never

133

2816

2949

Total

156

3120

3276

The 5-yr CIR (relative risk) of MI among users of OC for greater than 10 years
compared to never users is (7/46) / (133/2949) = 3.4.
The 5-yr CIR (relative risk) of MI among users of OC for greater than 10 years
compared to users of 5-9 years is (7/49) / (7/134) = 2.7

Case-Control Studies
Participants are selected for study participation on the
basis of pre-existing disease status
Cannot estimate prevalence, CI, or IR
Do not know the population at risk

Cannot use previous formulas

Relative risk can be estimated by odds ratio (OR)
ratio of odds of exposure among cases to odds of exposure
among controls

OR = (a/c)/(b/d) = ad/bc

Case-control: Looking Back

Yes
Exposure
Yes
No
Disease

Yes

Exposure
No

No

Example #3: Odds Ratio

Example adapted from Kehrberg et al 1981 AJE

Toxic shock syndrome

Tampon brand
used during
month of illness

Cases

Controls

Total

Rely

15

14

(29)

Other

45

(54)

Total

24

59

(83)

OR = (15*45)/(14*9) = 5.4
Interpretations:
The odds of using Rely tampons among women with TSS were
5.4 times higher than the odds of using Rely tampons among
those without TSS (technical)
Women who used Rely tampons were 5.4 times more likely to
develop toxic shock syndrome than women who used other
brands (loosely).

Notes on Odds Ratios

Can be thought of as exposure odds ratio
These data provide an estimate of risk in some situations.
They do not allow one to estimate incidence of TSS in the
population of women at risk.
To do this, one would need to know the number of all cases
of TSS among women (numerator) and the number of all
women who are at risk (denominator).
Usually, denominator data are not available and numerator
data may be incomplete in case-control studies.

Odds Ratio Approximates Relative Risk

When disease is rare
Proportion of cases in exposed and unexposed groups is low
a<<b, so a+b b and c<<d, so c+d d
RR = a/(a+b)/c/(c+d) a/b / c/d = ad/bc

If disease is not rare:

When cases are newly diagnosed
When prevalent cases are excluded, making it more like a
cohort/ incidence study

Comparing Differences

Difference (Absolute) Comparisons

Based on difference between 2 measures of frequency
Comparing disease occurrence among the exposed with
the disease occurrence among the unexposed
comparison group by subtracting one from the other.

Gives information on:

the absolute effect of exposure on disease occurrence
the excess disease risk, or disease burden, in the exposed
group compared to the unexposed group
the public health impact of an exposure, that is, how much
disease would be prevented if the exposure were removed

Note: this assumes that the exposure causes the

disease

Risk Difference
Risk difference (RD) = Rexp Runexp
For Prev*: RD = Pexp - Punexp = a / (a+b) c / (c+d)
For CI: RD = CIexp - CIunexp = a / (a+b) c / (c+d)
For IR: RD = IRexp - IRunexp = a / PTexp c / PTunexp

* Some epidemiologists hesitate to use risk when referring to

prevalence estimates
More precisely called prevalence difference, cumulative incidence
difference, and incidence rate difference
Also called attributable risk, rate difference, attributable rate
Note: attributable implies causality
RD = 0 when there is no association between exposure and disease

What we can hope to accomplish in reducing risk of disease among

exposed if exposure were eliminated

Example #4
(adapted from Boice 1977 JNCI)

Breast
cancer cases

PY

Rates per
10,000 PY

Radiation exposure

41

28,010

14.6

No radiation
exposure

15

19,017

7.9

Total

56

47,027

11.9

IRD = 6.7 / 10,000 PY

Interpretation:
Broad: there are 6.7 excess cases of breast cancer for every 10,000 PY
among those exposed to radiation compared to those not exposed.
Narrow: Eliminating this radiation would prevent 6.7 cases of breast
cancer for every 10,000 PY (attribution).

Example #5: Comparison of RR and RD

Annual Mortality Rate Per 100,000

Lung Cancer

Coronary Heart
Disease

Cigarette Smoker

140

669

Non Smoker

10

413

RR

14.0

1.6

RD

130/100,000/YR

256/100,000/YR

Conclusion: Cigarette smoking is a much stronger risk factor for lung

cancer but (assuming smoking is causally related to both diseases) the
elimination of cigarette smoking would prevent far more deaths from
coronary heart disease. Why is this so?
Death from CHD is much more common.

In Other Words
Relative risk is a measure of strength of association
between exposure and disease and is useful in analytical
studies
risk

Relative difference is a measure of how much disease

incidence is attributable to exposure, and is useful in
assessing exposures public health importance
burden

Population Risk Difference (PRD)

Measures excess disease occurrence among the total
population that is associated with the exposure.
Helps to evaluate which exposures are most relevant to the
health of a target population.
Describes impact of exposure on total population
Number of cases that would be eliminated in total population if
exposure was removed (assuming causality)

Depends on prevalence of exposure in population

For ex, PRD will be low if exposure is rare, even if RR is high

Also called population attributable risk

Calculating Population Risk Difference

Two formulas for PRD:
PRD = Rt - Ru

where Rt = risk total population and

Ru = risk among unexposed

PRD = (RD)*(PPexp) where PPexp is % of population

that is exposed
Note (as always) that risk may refer to IR or CI (more
accurately) or prevalence (less accurately)

Example #4 Revisited
Breast cancer
cases

PY

Rates/10,000 PY

Radiation exposure

41

28,010

14.6

No radiation exposure

15

19,017

7.9

Total

56

47,027

11.9

PRD = 11.9 7.9 = 4

Interpretation:
4 excess breast cancer cases for every 10,000 PY of
observation can be attributed to radiation exposure.
If radiation causes breast cancer, then 4 cases of breast cancer
for every 10,000 person-years of observation could be
prevented if the radiation exposure were removed.

Attributable Proportion among Exposed

APe describes the proportion of disease among exposed that is due

(attributable) to exposure or that would be prevented if exposure were
eliminated
Risk in non-exposed group can be considered background incidence that
would occur regardless of exposure
Interpretation may assume causal relationship

APe = [(Re Ru)/Re] * 100

= RD / Re * 100

Re = risk (IR, CI, P) among exposed

Ru = risk (IR, CI, P) among unexposed

Also called etiologic fraction, attributable risk percent, attributable risk

among exposed

Alternative formula
Again, we are interested in the difference between the risk
in the exposed and risk in the unexposed:

APe = [(Re Ru)/Re] * 100

Divide numerator and denominator by Ru
APe = [(RR-1)/RR] * 100
(Different formulas may be helpful depending on what
information you have.)
32

Note on alternative formula:

Especially useful for case-control data
You cannot estimate risk directly
Can use OR to estimate RR under certain conditions.
In which case:

APe = [(OR-1)/OR] * 100

33

Example
(continued)

Breast cancer
cases

PY

Rates/10,000 PY

Radiation exposure

41

28,010

14.6

No radiation exposure

15

19,017

7.9

Total

56

47,027

11.9

APe = [(14.6 7.9)/14.6] * 100 = 46%

Interpretation: 46% of cases of breast cancer among those exposed
to radiation may be attributed to radiation exposure and could be
eliminated if exposure were removed.

Attributable proportion among total population

APt describes the proportion of disease among total population that would
be eliminated if exposure were eliminated

What percent of disease in total population is due to exposure

Useful for setting priorities for public health action

Elimination of exposure lead to what impact on population?

Assumes causal relationship

APt = [(Rt Ru)/Rt] * 100

= PRD / Rt * 100
Rt = risk (IR, CI, P) among total population
Ru = risk (IR, CI, P) among unexposed

Also known as population attributable risk percent

Alternative formulas
APt = [1 - (Ru / Rt)] * 100
APt = [(Pe)(RR-1)]/[(Pe)(RR-1)+1] * 100
For case-control studies:
APt = [(Pe)(OR-1)]/[(Pe)(OR-1)+1] * 100

where Pe = proportion of exposed controls

(Convince yourself with some algebra if you like.)

36

Example
(continued)

Breast cancer
cases

PY

Rates/10,000 PY

Radiation exposure

41

28,010

14.6

No radiation exposure

15

19,017

7.9

Total

56

47,027

11.9

APt = [(11.9 7.9)/11.9] * 100 = 34%

Interpretation:
34% of breast cancer cases in total study population may be attributed
to radiation exposure and could be eliminated if exposure were
removed.
37

Key points
Relative and absolute measures of comparison tell us
different things
Relative risk is a measure of strength of association; often of
interest to epidemiologists who do etiologic research
Absolute risk then becomes important (assuming causality) to
public health planners, policy makers, etc. for estimating public
health impact of exposures on communities

Measures go by different names and multiple formulas

are sometimes available. It is important to
know what you are interesting in measuring,
know what data are available and in what form, and
if data are not available, know how to collect appropriate data.