Measures of Association

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Session five

Measure of association in
epidemiological studies

BY:

Sisay S. (BSc, MPH in Epidemiology)


July, 2022

7/11/2022 Sisay S (Bsc., MPH in Epidemiology) 1


• Learning objectives
• List common measures of association and measures
of public health impact

• Calculate and interpret risk ratio and odd ratio and


describe their use.

• Calculate and interpret attributable risk and risk


percent and describe their use.

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 2


• Association
• Exposure Outcome

• Is there a relationship between the exposure and


the outcome of interest?

• What kind?

• How strong?

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 3


• Definition
• Association: is a statistical relationship between two
or more variables.

• Requiring comparing two group.


– Exposed Vs unexposed

– With outcome Vs without outcome

• It quantifies the relationship b/n exposure and

outcome variables

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 4


• Exposure
• It is an explanatory factor; any potential health
determinants; the independent variable

• Example
– Ingestion of contaminated foods

– Sharing needles, drinking alcohol

– Genetic factors

– Getting education about certain behavioural change

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 5


• Outcome
• Disease:
– Infectious disease like malaria on non-infectious disease
like DM, cancer

• Events:
– Car accidents, immigration, poverty etc…

• Death:

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 6


• Why do we need them?
• Move from descriptive to analytical epidemiology.

• Comparisons within and between populations.

• Risk factor identification.

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 7


• Epidemiological data often presented in the form of two
by two (contingency) table.

• A 2x2 table contains 4 cells = a, b, c and d


Disease
Yes No Total
Yes a b a+b
No c d c+d
Total a+c b+d a+b+c+d

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 8


Cont…
• a= Number of individuals who are exposed and have
the disease

• b= Number of individuals who are exposed but not


have the disease

• c=number of individual who are not exposed but have


the disease

• d=number of individuals who are not exposed and do


not have disease
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 9
• Cont…
• a+b = the total number of individuals exposed

• c+d = the total number of individuals who are not exposed

• a+c = the total number of individuals with disease

• b+d = the total number of individuals without disease

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

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 10


• Strength of association is assessed by:
• Ratio Measures: relative risk

• Difference Measures: excess risk

• These measures may be applied at:


• Individual Level

• Population Level

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 11


• Ratio Measures includes:
• Relative risk

• Odd ratio (depending on the type of study design)

• Relative risk (risk ratio) (RR) for:


• Cohort study and experimental study

• Odd ratio (OR) for:


• Case control, cross sectional studies

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 12


• Relative risk/risk ratio (RR):
• It compare the occurrence of disease or risk factor
among two group using ratio.
• It is often measured / calculated from data presented in a
two by two table.
• It indicate the likelihood of developing disease in
exposed relative to non exposed.
• Compare the new occurrence (incidence) of disease
among exposed and non exposed.
• Indicate the strength of association b/n exposure and
outcome.
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 13
• Two-by-Two Table (Contingency Table)

• Relative risk = Incidence of disease among exposed


Incidence of disease among non exposed

• RR= Risk in exposed (a/(a+b))


Risk in unexposed(c/(c+d))
7/11/2022 14
Sisay S. (Bsc. MPH in Epidemiology)
• Cont…

• It indicates the likelihood of developing the disease


in the exposed group relative to those who are not
exposed.

• It is direct measure of risk.

• It usually used in cohort and experimental study


design

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 15


• Interpretation of RR
• The value of RR ranges between 0 and infinity.

• RR always a positive number.

• RR = 1
• No association b/n the risk factor (independent
variable) and the outcome (dependent variable).

• That means the risk acquiring the disease is the same


for those subjects with risk factor and without the

7/11/2022
risk factor Sisay S. (Bsc. MPH in Epidemiology) 16
• RR =/= 1,
• There is an association

• RR > 1 indicates that the risk of acquiring the disease is


greater among subject with risk factor than among
without the risk factor.

• RR < 1 indicate the risk of acquiring the disease is less


among with risk factor than among subject without the
risk factor

• Suggests that the factor exposure may be protective

7/11/2022
– i.e exposure associated with decreased risk
Sisay S. (Bsc. MPH in Epidemiology) 17
• RR come nearer to 1 (nullifying point) then the
association is said to be weak association.

• If RR is 3.0 or more association is high

• 1.5 to 2.9 association is moderate

No association
0 1
Preventive Risk

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 18


• Example 1:
• Table shows data from a cohort study of oral contraceptive
(OC) use and MI among women aged 16-49 years.
MI
Yes No Total
Yes 27 455 482
No 77 1831 1908
Total 104 2286 2390

• Calculate RR?

• Give interpretation for the result?


7/11/2022 19
Sisay S. (Bsc. MPH in Epidemiology)
• Solution
• RR= Ie/Io

• Ie = 27/482 = 0.056

• Io = 77/1908 = 0.040

• RR = 0.056/0.040 = 1.4

• Interpretation: Women who used oral contraceptive


had 1.4 times higher risk of developing MI when
compared from non oral contraceptive users.

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 20


• Example 2:
• A study conducted on postmenopausal hormone use
and coronary heart disease, after a total of 54, 308.7
person years follow up for a hormone users, 30
developed CHD and 60 develop CHD from 51, 477.5
person years follow upamong non hormone users.

• Calculate RR?

• Give interpretation?

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 21


• Solution
• RR = Ie/Io
• RR = IDe/Ido
• IDe = No. new cases among exposed/ Person years among exposed
group
= 30/54, 308.7 = 0.0006
• IDo = No. new cases among non exposed/ Person years among non
exposed group
= 60/51,477.5 = 0.0012
• RR = 0.0006/0.0012 = 0.5
• Interpretation: women who use postmenopausal hormone had 0.5
times less risk of developing CHD when compared from non users.

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 22


• Odd Ratio (OR)
• It is an indirect measures of a risk in disease of rare
occurrence

• It is usually used in case control and cross sectional study


design

• Cases and controls are predetermined and we are calculating to


determine whether cases or controls are more exposed to
postulated risk factors

• Indicates the likelihoods of having an exposure among cases


relative to controls
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 23
• Odd Ratio…
• Odds are calculated by dividing the probability of the
event by the probability that it will not occur.

• The probability of an event in a study population is


P(X=x) and, the probability that the event will not
occur is (1- P(X=x)).

• The odds of the event occurring in the study


population can, therefore, be expressed in the form
P(X=x)/ (1-P(X=x))
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 24
• Odd Ratio…

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 25


• Odd Ratio…

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 26


• Odd Ratio…

• Hence: OR = (a/c)/(b/d)

• Which can be simplified to


– OR = ad/bc

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 27


• Interpretation of OR
• The value of OR ranges between 0 and infinity.

• OR always a positive number.

• OR = 1
• No association b/n the risk factor and (independent
variable) and the outcome (dependent variable).

• That means the odds of acquiring the disease is the


same for those subjects with risk factor and without

7/11/2022
the risk factor Sisay S. (Bsc. MPH in Epidemiology) 28
• OR =/= 1,
• There is an association
• OR > 1 indicates that the odds of acquiring the disease
is greater among subject with risk factor than among
without the risk factor.
• OR < 1 indicate the odds of acquiring the disease is
less among with risk factor than among subject without
the risk factor
• Suggests that that the factor exposure may be
protective

7/11/2022
– i.e exposureSisay
associated with decreased risk
S. (Bsc. MPH in Epidemiology) 29
• OR come nearer to 1 (nullifying point) then the
association is said to be weak association.
• If OR is 3.0 or more association is high
• 1.5 to 2.9 association is moderate
• The further away from 1 the stronger the
association between exposure and disease.
No association

Preventive Risk
0 1
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 30
• Example 1: table shows data from case control study of
oral contraceptive (OC) use and mycocardial infraction
in pre-meneopausal female nurses.
Myocardial infarction
Current Yes No Total
OC
Yes 23 304 327
Use
No 133 2816 2949

Total 156 3120 3276

• Calculate OR?

• Give interpretation?
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 31
• Solution:
• OR = ad/bc

= (23)*(2816)/ (133)*(304)

= 1.6

• Interpretation: the odds of developing MI among


oral contraceptive users is 1.6 times higher compared
from non-oral contraceptive users.

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 32


• Example 2: Researchers select 100 patients with colon cancer
and 300 patients without colon cancer. Of the 100 patients
with colon cancer, 20 smoke cigars while 30 of the 300
patients without colon cancer smoke cigars.
Colon cancer
Yes No Total
Smokers (exposed ) 20 30 50
Non smokers (non exposed) 80 270 350

Total 100 300 400

• Calculate OR?

• Give interpretation?
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 33
• Solution:
• OR = ad/bc

= (20)*(270)/ (80)*(30)

= 2.25

• Interpretation: the odds of developing colon cancer


among cigarette smokers is 2.25 times higher
compared from non cigarette smokers.

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 34


• RR can be estimated by OR if the following
condition are fulfilled:
• The controls are representative of the general
population

• The selected cases are representative of all cases

• The disease is rare

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 35


• Difference Measures: excess risk

• Attributable risk (AR)/risk difference (RD)


• It measures absolute effect of the exposure or the excess risk of
disease in those exposed compared with those who are not exposed.

• The amount of disease that can be attributed to a certain exposure

• Quantifies the expected reduction in disease occurrence if harmful


exposure could be eliminated

• AR= incidence among exposed (Ie) – Incidence among non


exposed(Io)

• Measures public health impact of disease attributed by the certain


exposure in the exposed group
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 36
• AR…

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 37


• AR…

• It important for
• Policy decision

• Funding decision (E.g. prevention program)

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 38


• Example:
• Table shows data from a cohort study of oral contraceptive (OC)
use and MI among women aged 16-49 years.

MI
Yes No Total
Yes 27 455 482
No 77 1831 1908
Total 104 2286 2390

• Calculate AR for the following table


• Give interpretation?
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 39
• Solution
• AR = Ie – Io
= 27/482 – 77/1908
= 0.0156 = 156/10, 000

• Interpretation:
• Among 10, 000 oral contraceptive users 156 cases are
attributed due to use of oral contraceptive
• We can prevent 156 cases among oral contraceptive
user by elimination oral contraceptive use
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 40
• Attributable risk percent (AR%)
• Estimate the proportion of the disease among the exposed
that is attributable to the exposure, or

• The proportion of the disease in the exposed group that could


be prevented by eliminating the exposure.

AR% =(Ie-Io) x 100

Ie
• From above example calculate AR%?

• Give interpretation?
7/11/2022 41
Sisay S. (Bsc. MPH in Epidemiology)
• Population attributable risk (PAR):
• Measures the excess risk among the general population
that is due to exposure of interest

• PAR = Risk in population -Risk in unexposed

• PAR = AR x Proportion of exposed in the population

• Measures public health impact of an exposure

• Estimate the excess rate of disease in the total study


population that is attributable to the exposure.

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 42


• Example: research was conducted to assess the
association between cigarette smoking and death
from lung cancer. The following finding were
obtained.
• AR = 89 per 100,000 per year

• Prevalence rate of cigarette smoking = 20%

• Calculate PAR?

• Give interpretation?
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 43
• Both AR and PAR are used to estimate the effect of
disease incidence of eliminating a given risk factor,

• AR estimate reduction in disease incidence only in


those exposed,

• PAR estimates reduction in disease incidence in the


population as a whole.

7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 44


• Population attributable risk percent (PAR%)
• 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.

PAR% = PAR x 100

incidence rate in total population

• Example: PAR = 17.8 per 100,000 per year

• Mortality rate in the total population 24.8 per 100.000

• Calculate PAR%

• Give interpretation ?
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 45
• Exercise
– 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.
Prevalence of anemia among the population is 15%.
• Name the exposure and outcome variable.
• What kind of study is appropriate?
• Calculate the appropriate measures of association and give interpretation.
• Calculate the AR and give interpretation.
• Calculate the PAR and give interpretation.
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 46
• Possible out came in studying the relationship between
disease and exposure
• No association between exposure and disease

– AR = 0, RR = 1

• Positive association between exposure and disease(more


exposure, more disease).

– AR>0, RR>1

• Negative association between exposure and disease(more


exposure, less disease).

– AR<0,(Negative), RR<1(fraction)
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 47
• Absolute Risk Reduction (ARR)
• Absolute difference in the rates of events between the
two groups

• It gives an indication of the baseline risk and


treatment effect

• ARR = 0 means there is no difference between the


two groups therefore the treatment had no effect.

48
• Cont…
• ARR = risk of the outcome in the control group - risk of
the outcome in the treatment group.

• This is also known as the absolute risk difference.


• Example: A researcher include outcomes of cancer after two
years of treatment by the new drug, which is 15% (0.15) of the
control group died and 10% (0.10) of the treatment group
died.
– RR = 0.10/0.15 = 0.67

• Interpretation: Since the RR < 1, the treatment decreases the


risk of death. 49
• Cont…

– ARR = 0.15 - 0.10 = 0.05 or 5%

• The absolute benefit of treatment is a 5% reduction in the


death rate.

50
• Relative Risk Reduction (RRR)
• Is the complement of the RR

• It is protective efficacy of the treatment

• Most commonly reported measure of treatment


effects

• It tells us the reduction in the rate of the outcome in


the treatment group relative to that in the control
group

51
• Cont…
• RRR= absolute risk reduction / risk of the outcome
in the control group. An alternative way to calculate
the RRR subtract the RR from 1 (RRR = 1 - RR)
– From above example the RRR = 0.05/0.15 = 0.33 or 33%

– RRR = 1 - 0.67 = 0.33 or 33%

• The treatment reduced the risk of death by 33%


relative to that occurring in the control group.

52
• Number Needed to Treat (NNT)
• It represents the number of patients we need to treat

with the experimental therapy in order to prevent 1 bad

outcome

• It incorporates the duration of treatment.

• Clinical significance can be determined to some extent by

looking at the NNTs, but also by weighing the NNTs

against any harms or adverse effects of therapy.

53
• Cont…
• NNT = inverse of the ARR and is calculated as 1 /
ARR

• From above example NNT = 1/ 0.05 = 20

• We need to treat 20 people for 2 years in order to


prevent 1 death.

54
• Precise of estimate on treatment effect
• Looking at the confidence intervals (CI) for each estimate

• If the confidence interval is fairly narrow the estimate is a


precise reflection of the population value.

• It also provides information about the statistical


significance of the result.

• If the value corresponding to no effect falls outside the


95% confidence interval then the result is statistically
significant at the 0.05 level.

55
7/11/2022 Sisay S. (Bsc. MPH in Epidemiology) 56

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