PART 2:

Attributable Risk - assessing the potential effects of prevention programs in public health
How much of a disease can be attributed to a certain exposure in the exposed group?

How much of the risk (incidence) can we hope to prevent if we are able to eliminate exposure to the

risk factor?

Incidence NOT due to exposure

Factors shared by both exposed and unexposed persons

Other factors other than "Exposure" - e.g. genetics, environment, etc

Excess incidence due to exposure

Calculating Attributable risk:

How much of the total risk in exposed persons is due to exposure (e.g. smoking)

In cohort study: everyone is free of disease at baseline, risk of developing disease in

each exposure and unexposed groups are incidence rates

***NOTE*** calculating (population) attributable risk in a population of 1000 is different than
%AR or %PAR
Attributable risk --> asking what proportion of the risk in exposed persons is due to exposure?

AR= [(incidence in exposed - incidence in unexposed)/Incidence in exposed]

Provides the potential for prevent if the exposure could be eliminated

E.g.

o
HOW MUCH OF THE TOTAL RISK IN EXPOSED PERSONS IS DUE TO EXPOSURE???
o
In 1000 people
risk in smokers = 28/1000

Risk in nonsmokers = 17.4/1000

THESE ARE INCIDENCE RATES

Attributable risk= (28-17.4)/1000 = 0.0106 = 10.6/1000

Interpretation in 1000 people

10.6 cases of CHD per 1000 smokers are attributed to smoking

If smokers were to quite smoking, we would prevent 10.6

cases of CHD per 1000 smokers

o
WHAT PORTION OF THE RISK IN EXPOSED PERSON IS DUE TO EXPOSURE
o
AR% = (28-17.4)/28=0.3786
Interpretation:

37.9% of CHD cases among smokers are attributable to smoking

If smokers were to quit smoking, we would prevent 37.9% CHD cases in these
people
Population Attributable Risk
What can we hope to accomplish in our population if we got smokers to stop smoking?

How much of a disease in the total population can be attributed to a certain exposure?

PAR = (incidence in total population - incidence in unexposed group)

What do we need to calculate PAR

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Incidence among exposed (smokers) - 28/1000 = 0.028 incidence rate

Incidence among unexposed (nonsmokers) - 17.4/1000
Proportion of the total population who smokers - 16% are smokers, 84% are non smokers

THUS:
Incidence (of disease) in total population = (Incidence in smokers)(%smokers in population) +
(incidence in nonsmokers)(%non smokers in population)
==> (28/1000)/(0.16) + (17.4/1000)(0.84) = 19.1/1000
Example:
PAR = 19.1/1000 - 17.4/1000=0.0017 =1.7/1000
in the population of smokers and non-smokers, 1.7 cases of CHD per 1000 people are attributable t

smoking
An effective smoking cessation program would, at best, prevent 1.7 cases CHD per 1000 people in

this population
PAR%=19.1-(17.4/19.1)= 0.089
In the population of smokers and nonsmokers, 8.9% of incidence of CHD can be attributed to

smoking
An effective smoking cessation program would, at best reduce the incidence of CHD by 8.9% in this

population
RR vs. PAR
RR

Used to measure the strength of

association
o
Used to help assess causation
Important: does NOT say that

exposure X CAUSES diseases Y

AR/PAR
o
Used to assess the potential effect of the
prevention programs in public health

Person-Years
Calculations of RR assumes that each person in the study has been followed-up for the same amount of
time.
Oftentimes though this isn't true: drop outs, not everyone enters the study at the same time

Person years corrects this situation about follow up times.

Definition of person-years:
The amount of follow-up time in years that each person

contributes to the study

Computation begins on the day person enters study

Computation ends on one of the following days:

o
Last day that data is available for persons who
drop-out
o
Day person is diagnosed with disease of interest
o
Last day of study (last day of follow-up
Note that each person can contribute different
amounts of exposure times equating to total years at risk for example
Measures both # of persons and time followed for each person
1 person followed for 10 years = 10 people each followed for 1 year
o

Incidence density (ID) = Number of cases/total person years (P-Ys)

Ex. 2 cases in 16.5 P-Ys
Incidence density (ID) = 2 cases/16.5 P-Ys

ID=0.121/1 P-Y or 12.1/100 P-Ys

Thus incidence is 12.1 cases of diseases per 100 person years of follow-up

Incident Density Ratio

Calculate P-Ys separately for exposed and unexposed groups
1 In exposed group:
a ID = 40 causes/1000 P-Ys
2 In unexposed group:
a ID=15 cases/1000 P-Ys
b IDR=ID_exposed/ID_unexposed=2.67
THUS: incidence of disease in the exposed group is 2.67 times the incidence of disease in the unexposed
group
Cross-sectional Studies - at a specific incidence, what's the exposure and disease
1 Identify subjects' exposure and disease status at the same point in time (no follow-up)
2 Identify prevalent cases of disease
a People who have the disease at the time of the assessment (new cases would be incidence)
2 Can calculate:
a Prevalence of disease in exposed
b Prevalence of disease in unexposed
E.g.: Exposure=serum cholesterol

Disease = CHD

At the same physician visit, determine serum cholesterol

levels and do an ECG to assess the presence of CHD

Cross-sectional studies - calculations:
Calculations identical to cohort study instead with prevalence

o
Prevalence Ratio = Prevalence of disease in
exposed/prevalence of disease in unexposed
o
Comparing the prevalence of exposed group to that of unexposed group, thus it's not the
prevalence of the disease as a whole, but rather just how much the exposure changes the
relative prevalence
Can we calculate RR?? NOPE

o
Concept of risk doesn't apply in cross-sectional studies (since we are looking at prevalent
cases
o
Some subjects already have the disease
No longer "at risk" of disease

o
Subjects without diseases are not being followed-up to assess risk
In Cohort study:

o
All subjects are disease free at baseline
o
All subject are "at risk" of developing diseases
o
All subjects are followed-up over time
Interpreting Prevalence Ratio if it is 1.40:
"Prevalence of disease in the exposed group is 40% higher than the prevalence of disease in the

unexposed group"
Interpretation similar to RR, but we're dealing with (relative) "prevalence" of disease, not risk of

disease
STRENGTHS AND WEAKNESSES of cross-sectional studies
Strengths
1 Quick and cheap (e.g. survey)
2 Useful for exploratory analyses, early tests of hypotheses, hypothesis generation
3 Results may suggest the need for case-control or cohort studies
Weaknesses
1 Reverse causality bias
a E and D assessed at the same time
b Can't be sure if E preceded D or viceversa
2 Prevalent cases may not be representative of all cases
a More likely to be cases of long duration (different from case of short duration?)

Could be cases who survived the disease (association is NOT exposure leading to diseases, but
Exposure leads to SURVIVING the disease

Nested Case-Control Study

Conducted within large cohort studies using exposure data that are collected at baseline ("nesting")

At some point during follow-up, some subjects will develop a diseases (case)

Select one or more persons who are disease-free (controls_ at the time when each case is

diagnosed
Go back to baseline data and assess exposure status of cases and controls

Controls are time-matched to cases

o
Matching must be accounted for in the analysis
ADVANTAGES:

o
Exposure data were obtained when subjects were disease-free
o
Subjects don't have to recall long-ago exposures (eliminates recall bias)
o
Cheap to conduct
Case-Cohort Study
Also conducted within large cohort studies

Variant of nested case-control study

Includes all cases and random sample of entire cohort (controls+cases)

o
Random sample = "sub cohort"
o
Cases and controls are not time-matched
o
Subcohort selected without knowledge of case status
o
"truly" representative of study case; person-time that
give rise to the case

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Advantages of casecohort study:

Efficient - not all members
of parent cohort require
diagnostic testing
Flexible - allows testing
hypotheses not
anticipated when cohort
was drawn (t0)
Reduces selection bias - case sand non-cases sampled from same population
Reduced information bias - risk factor exposure can be assessed with investigator blind case status

Disadvantages of case-cohort study:

1 Increased potential for information bias because subcohort may have been established after T0
2 Exposure information collected at different times (e.g. potential for sample deterioration)
SUMMARY:
1 Prospective cohort studies allow calculation of incidence ratios; case-control studies don't
2 PAR estimates how much of a disease in the total population can be attributed to a certain exposure
3 Cross-sectional studies can't determine temporality
4 Case-control, nested case-control, and case-cohort studies are efficient ways to estimate incident rate
ratios
CASE EXAMPLES--- not necessary I guess
Cross sectional study example:
Example: does breastfeeding affect the risk of obesity and being overweight in children at the time of entry
to school?
Cross-sectional survey to assess the impact of breastfeeding on the risk of obesity and being

overweight in children at the time of entry to school

Ask if you were breast fed, ask for weight and calculate bmi

Nested case control example:

Prospective analysis of 7.5 year long randomized trial (pool groups)

At baseline, plasma concentration fo fatty acids were measured (before cancer developed)

During followup, 250 incident cancer cases

Thus: select 250 controls with FA measurements

Have prospective cohort study to study determinants of CVD and cancer n=90000
After enrolment, collect exposure data on all women

Women agree to provide adipose tissue samples at baseline

These women followed for 8 years

"are adipose tissue TFA associated with heart disease?"

After 8y followup, 1439 of women developed heart diseases

90000 provided blood samples

It cost $200 to analyze each adipose sample for total FA content --> $18million

Efficient way: CHD cases were only 1.6% of the population

Analyzing all adipose samples from women who developed CHD but only a sample of the whole
cohort in order to estimate the exposure distribution in the population that produced the cases
Try 2:1 matching