Estimating Risk: Is there an association?

Review of designs
How do we determine whether a certain disease is associated with a certain exposure
Relative risk
Odds ratio

How do we determine whether a certain disease or outcome is associated with a certain

exposure
 by computing either the ratio or the difference
 ratio: it is the exposed all over the unexposed
 difference: it is exposed minus the unexposed

If an association exists in a cohort study, how strong is it?

What is the ratio of the risk of disease in exposed individuals to the risk of disease in
nonexposed individuals?
 So let us say that you are conducting a cohort study. So if an association exists
in a cohort study, how strong is this association? So we said that the more
common way to assess risk would be to determine the ratio
 Question: What is the ratio of the risk of the disease in exposed individuals to the
risk of disease in non exposed or unexposed individuals?
o When you take a ratio you should have two measurements: those who are
exposed all over those who are unexposed

Figure 2. Relative risk ratio. The risk in the exposed all over the risk in the unexposed.
We can calculate the ratio and this is known as the relative risk or risk ratio (RR). If you
calculate this ratio, you will get a certain figure and that is the relative risk.
 Absolute risk: The incidence
 The incidence in the exposed all over the incidence in the unexposed

How do we interpret the value of a relative risk (RR)?

 Relative risk ratio: Very important because this is how the result is presented in
scientific journals

Interpreting the value of a relative risk

 If RR =1 Risk in exposed equal to risk in non—
exposed
(no association)

If RR >1 Risk in exposed greater than risk in non-

exposed
(positive association; possibly causal)

If RR < 1 Risk in exposed less than risk in non-

exposed
(negative association; possibly protective)

Relative risk (RR) = 1

 The risk in the exposed is equal to the risk in the unexposed
 The result is 1 or exactly one
 There is no association between the exposure and the outcome

Relative risk (RR) > 1

 The numerator is greater than the denominator
 The risk in the exposed (numerator) is greater than the risk in the nonexposed
(denominator)
 There is a positive association between the two
 The higher the exposure the higher will be the outcome or the greater the exposure
the greater will be the outcome
 Positive association, possibly causal not definitely
 Possible causal association

Relative risk (RR) < 1

 The risk in the exposed is less than the risk in the nonexposed/unexposed
 The numerator is less than the denominator
 There is an association but it is negative
 The higher the exposure the lower will be the outcome
 Inverse relationship or inverse proportion
 Possibly protective
o Just like a vaccine
o You will want the result of the vaccine trials to have an RR are less than 1
because you want the vaccines to be protective

We can calculate the relative risk from a cohort study

Then follow to see whether

Totals
Disease Disease does
develops not develop

First select Exposed a b a+b

 Not exposed c d c+d

Incidence rate of exposed: a / a + b

Incidence rate of unexposed: c / c + d

 First we select now those individuals who are exposed and those who are not
exposed and then we follow them up over time to determine Whether disease
develops or disease does not develop.
 Count the number of individuals:
o Letter A will represent the number of individuals who are exposed and who
developed disease
o Letter D will represent those who are not exposed and did not develop
the outcome or did not develop the disease
 To calculate the relative risk
o Incidence rate of the exposed (numerator): a all over a plus b
o Incidence of the unexposed: c all over c plus d

Hypothetical cohort study

Association between smoking and coronary heart disease

Then follow to see whether

Totals
CHD does not
CHD develops
develop

Smoke 84 2,916 3000

First select
Do not smoke 87 4,913 5000

Relative risk
=(risk of exposed)/(risk of unexposed)
=1.61 (greater than 1)
There is a positive association between smoking and coronary heart disease
Interpretation:
The risk of coronary heart disease is 1.61 times greater (or higher) among those who
smoke, as compared to those who do not smoke.
 Exposure: smoking
 Outcome: coronary heart disease
 84 individuals who are smokers and those who develop coronary heart disease
 87 individuals were non-smokers, but they still develop coronary heart disease
 Excess risk would be the excess of 1 so that would be 61 percent
o There is a 61 percent greater chance of getting coronary heart disease among
smokers as compared to those who do not smoke
o As a ratio, you will say 1.61 times higher
ASSOCIATION BETWEEN SERUM CHOLESTEROL AND CORONARY HEART DISEASE

MEN WOMEN

Serum
30-49 50-62 30-49 50-62
Cholesterol
y/o y/o y/o y/o
(mg/dL)

Incidence rates (per 1,000)

<190 38.2 105.7 11.1 155.2

190-219 44.1 187.5 9.1 88.9

220-249 95.0 201.1 24.3 96.3

250+ 157.5 267.8 50.4 121.5

Relative risks

<190 1.0 2.8 0.3 4.1

190-219 1.2 4.9 0.2 2.3

220-249 2.5 5.3 0.6 2.5

250+ 4.1 7.0 1.3 3.2

 main or the fundamental variable: age and sex

 the association between cholesterol and coronary heart disease will be better
appreciated looking at the relative risks rather than the incidents
Assign a baseline value: usually the lowest value where everything else is compared
against to
 38.2 (assigned baseline; in red)
 44.1 / 38.2 = 1.2
o Relative risk is 1.2 for serum cholesterol ranging from 190 to 219
o The risk of coronary heart disease is 1.2 times higher among those with
serum cholesterol ranging from 190 to 219 milligram per dL, as compared to
those with less than 190 milligram per dL
 95 / 38.2 = 2.5
o With increasing cholesterol, the relative risk is also increasing that will further
strengthen your conclusion that there is an association between serum
cholesterol and coronary heart disease
o The higher the cholesterol, the greater the risk of CHD
 Interpretation for 4.1: So the risk of coronary heart disease is 4.1 times higher or
greater among those with serum cholesterol greater than 250 milligrams per DL as
compared to 190 milligrams per dL
CHECKPOINT
(T/F)
1. The relative risk can also be defined as the probability of an event (developing a
disease) occurring in exposed people compared to the probability of the event in
nonexposed people, or as the ratio of the two probabilities.
2. In a cohort study, to answer the question of whether there is an association between
the exposure and the disease, we can either use the relative risk discussed in the
previous section or we can use the odds ratio (also called the relative odds).
3. If the relative risk is equal to 1, the numerator equals the denominator, and the risk
in exposed persons equals the risk in nonexposed persons. Therefore, no evidence
exists for any increased risk in exposed individuals or for any association of the
disease with the exposure in question.
4. If the relative risk is less than 1, there is an association of the disease with the
exposure but it is negative.
5. There is an inverse relationship or inverse proportion when the relative risk is less
than 1
6. There is a positive association, possibly causal association when RR is greater than 1.

ANSWERS
1. True
2. True
3. True
4. True
5. True
6. True