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Measurement in Epidemiology
By Mengistu Handiso (MPHE)
Prepared by Mengistu H(MPHE) 1
Outline
 Epidemiological measurement variables
 Measurement of disease occurrence in
population
 Mortality measures
 Measurement of association
 Evaluation of causation
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Measurement in Epidemiology
 Epidemiology is mainly a quantitative
discipline, so we should quantify health and
health related events.
 Epidemiological measurement variables
 Absolute number
 Ratio
 Proportion
 Rate
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 Measurement of disease occurrence in population
1. Incidence rate
 Cumulative Incidence
 incidence Density
2. Prevalence rate
 Point Prevalence
 Period Prevalence
 Measurement of mortality (death rate )
 Measurement of association
1. Risk ratio
2. Odd ratio,
3. Risk difference
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Measuring Disease Occurrence
Absolute number
 The number of cases(Absolute number ) in a
given community can give more epidemiologic
sense if they are related to the size of the
population.
 Such tie of the number of cases with the
population size can be determined by
calculating ratios, proportions, and rates
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Ratio x፡y
 Ratio: The value of x and y may be completely
independent. example (Male: Female)
Proportion x/ x+y
 Proportion: is a ratio (expressed as a percent)
in which x is included in y.
 Example Female/Both sexes
(proportion of female in a community)
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Rate
 Rate is a Proportion, it measures the
occurrence of an event in a population over
time.
 The time component is important in the
definition.
Measles cases in under five children in 1995
Under five children in 1995
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 Notice three important aspects of this formula.
1. The persons in the denominator must reflect
the population from which the cases in the
numerator arose.
2. The counts in the numerator and denominator
should cover the same time period.
3. In theory, the persons in the denominator
must be “at risk” for the event, that is, it should
have been possible for them to experience the
event
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Table1.1 Neonatal sepsis, Hospital A, Ethiopia, 2003
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The line listing in the Table 1.1 presents some of the
information collected on infants born at Hospital
A with neonatal sepsis.
1. What is the ratio of males to females?
2. What proportion of infants lived?
3. What proportion of infants were delivered in a
delivery room?
4. What is the ratio of operating room deliveries to
delivery room deliveries?
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Incidence rate
 Incidence rates are the most common way of
measuring and comparing the frequency of
disease in populations.
 It measures the rate at which people without
the disease develop the disease during a
specified period of time.
 The incidence rate expresses the probability or
risk of illness in a population over a period of
time.
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 Since incidence is a measure of risk,
when one population has a higher
incidence of disease than another, we
say that the first population is at a higher
risk of developing disease than the
second, all other factors being equal.
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 It is used to study disease aetiology
 Required data:
 period of observation;( Time)
 number of new cases; (n)
 time of disease onset (diagnosis Time );
 population at risk /denominator(N).
 The formula for calculating an incidence rate follows:
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 The numerator of an incidence rate should reflect
new cases of disease which occurred or were
diagnosed during the specified period.
 The denominator is the population at risk.
 This means that persons who are included in the
denominator should be able to develop the disease
that is being described during the time period
covered.
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Risk (Cumulative Incidence)
 Measures the risk (the likelihood, probability) that an
individual will contract the disease during a certain
time period or before a given age.
= New cases occurring during a given time period
Population at risk during the same period
 Cumulative incidence relates occurrences of new cases
to the population at the beginning of the study period.
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Example
 Two surveys were done of the same
community 12 months apart. Of 5,000 people
surveyed the first time, 25 had antibodies to
histoplasmosis.
 Twelve months later, 35 had antibodies,
including the original 25.
1. What is cumulative/ Incidence during the 12-month
period:
x = Number of new positives during the 12-month
period = 35 - 25 = 10
y = population at risk = 5,000 - 25 = 4,975
x/y . 10n = 10/4,975 x1,000 = 2 per 1,000
2. Prevalence at the second survey:
x = antibody positive at second survey = 35
y = population = 5,000
n
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Incidence Density
 Incidence density represents rate at which new
cases are occurring.
 Does not indicate the risk for any individual in a
population.
= New cases occurring in a specified period
Total person-time at risk in the same period
 An incidence measure is a speed, usually
expressed as number of cases per 1,000 or
100,000 units of follow-up time
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 The population at risk is dynamic and
each person in the population
contributes the amount of time that
they remained under observation and
free from disease (person-time)
 The numerator is still the number of new
cases, but the denominator is the sum of
the time each person is observed,
totalled for all persons.
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 Person-time rates are often used in
cohort (follow-up) studies of diseases
with long incubation or latency periods,
such as occupationally related diseases,
AIDS, and chronic diseases.
 Time unit=month, year, day
 person-time=person-year, person-
month,
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Example:-
 Investigators enrolled 2,100 men in a study
and followed them over 4 years to determine
the rate of heart disease.
 We assume that persons diagnosed with
disease and those lost to follow-up were
disease-free for half of the year, and thus
contribute ½ year to the denominator.
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Example
 Initial enrolment: 2,100 men free of disease
 After 1 year: 2,000 disease-free, 0 with
disease, 100 lost to follow-up
 After 2 years: 1,900 disease-free, 1 with
disease, 99 lost to follow-up
 After 3 years: 1,100 disease-free, 7 with
disease, 793 lost to follow-up
 After 4 years: 700 disease-free, 8 with
disease, 392 lost to follow-up
1. Identify x: x = cases diagnosed = 1 + 7 + 8 = 16
2. Calculate y, the person-years of observation
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 700 men x 4.0 years = 2,800 person-years
 8 + 392 = 400 menx3.5 years = 1,400 person-
years
 7 + 793 = 800 menx2.5 years = 2,000 person-
years
 1 + 99 = 100 menx1.5 years = 150 person-years
 0 + 100 = 100 menx0.5 years = 50 person-years
 Total = 6,400 person-years of observation
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Prevalence rate
 Prevalence, sometimes referred to as prevalence rate,
is the proportion of persons in a population who have
a particular disease or attribute at a specified point in
time or over a specified period of time.
 Numerator is number of existing cases
 Denominator is your population of interest
(including all those in numerator)
 The formula for presence of disease is:
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Point prevalence:-
Point prevalence is the amount of disease present
in a population at a single point in time.
Point prevalence =
all the cases of factor of interest at a given time
x10n
total population
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Period prevalence.
The numerator in period prevalence is the
number of persons who had a particular
disease or attribute at any time during a
particular interval (week, month, year, decade,
or any other specified time period).
Period prevalence =
all cases (old and new) of the factor of interest during the time period x
10n
average population during the given period of time
Exercise 2.4
 Recall that Figure 2.1 represents ten
episodes of an illness in a population of
20 over a period of 16 months.
 Each horizontal line represents the portion
of time one person spends being ill. The
line begins on the date of onset and ends
on the date of death or recovery.
28
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29
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Calculate the following rates:
a. Point prevalence on October 1, 1990
b. Period prevalence, October 1, 1990 to September
30, 1991
C, point prevalence on September 30,1991
30
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a. Point prevalence on October 1, 1990:
x = cases present on 10/1/90 = 6
y = population = 20
= x /y .10n=
6/20 × 100 = 30%
31
Prepared by Mengistu H(MPHE)
b. Period prevalence, October 1, 1990 to
September 30, 1991
x = cases present between 10/1/90 and
9/30/91 = 6 old case , 4 new case =10
y = population = 20
x/y × 10n =
 10 /20× 100 = 50%
32
Prepared by Mengistu H(MPHE)
C, point prevalence rate on September
30,1991
x= 6 old case, 4 new case , 5 death
x/y =6+4-5/20
= 5/20*100
= 25%
33
Prepared by Mengistu H(MPHE)
Calculation : in f/up {cohort study )
Incidence rate;-
 Subtract old case from denominator(risk
)
 Subtract dead, cure case from the
numerator=new case=point type)
Point Prevalence rate :-
 Subtract dead, cure case from the
numerator = (old &new case )=point
prevalence 34
Prepared by Mengistu H(MPHE)
In a study population of 1000 inhabitants there are 60
cases of tuberculosis and 20 cases of hypertension.
During the first six months there are 17 new cases of
tuberculosis and 8 new cases of hypertension. At the end
of the year the total of new cases is 27 for tuberculosis
and 13 for hypertension. During the same period, 8 new
cases of tuberculosis died and 8 were cured. In the same
period, 5 cases of hypertension died and no case of
hypertension was cured.
Calculate the following rates :-
1. -Prevalence rate at the beginning of the study
2. -Incidence rate A) tuberculosis and B) hypertension at the
end of the first six months
3. -Incidence rate of tuberculosis at the end of the year
4. -Prevalence rate of A)tuberculosis and B) hypertension at
the end of the year
35
Class work
Possible answer
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Characteristics of Prevalence
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Cause and effect measured simultaneously
-Impossible to infer causation
Useful for planning (e.g. beds, clinics, workforce
needs)
High prevalence  high risk
 could reflect increased survival(improved care,
behavior change - long duration)/old case
Low prevalence  low risk
 could reflect rapid fatal or cure process -
short duration)
Easy to obtain need only one measurement
Figure 3.2 Relationship between prevalence and
incidence
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Migration
Care,
behavioral
change ,
-Dx
Relationship between prevalence and incidence
 Prevalence is based on both incidence
(risk) and duration of disease.
P ≈ I*D
 High prevalence of a disease within a
population may reflect high risk, or it may
reflect prolonged survival without cure.
 Conversely, low prevalence may indicate
low incidence, a rapidly fatal process, or
rapid recovery.
Prepared by Mengistu H(MPHE) 39
Comparison of prevalence and incidence
 The prevalence and incidence of disease are
frequently confused.
 They are similar, but differ in what cases are
included in the numerator.
 Numerator of Incidence = new cases occurring
during a given time period
 Numerator of Prevalence = all cases present
during a given time period
 As you can see, the numerator of an incidence rate
consists only of persons whose illness began during
a specified interval.
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Prevalence rate increased by
•Longer duration of the disease
•Prolongation of life of patients
without cure.
•Increase in new cases
•Immigration of cases
•Out migration of health people
•In-migration of susceptible people
•Improved diagnostic facility
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Prevalence rate decreased by
•Shorter duration of disease.
•High case-fatality rate from
disease.
•Decreases in new cases (decrease
in incidence)
•In-migration of healthy people.
•Out migration of cases.
•Improved cure rate of case
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Attack Rate
 An attack rate is a variant of an incidence rate,
applied to a narrowly defined population observed
for a limited time, such as during an epidemic.
 The attack rate is usually expressed as a per cent, so
10n equals 100.
 For a defined population (the population at risk),
during a limited time period.
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 Of 75 persons who attended a church picnic, 46
subsequently developed gastroenteritis.
 To calculate the attack rate of gastroenteritis we
first define the numerator and denominator:
X = Cases of gastroenteritis occurring within the
incubation period for gastroenteritis among
persons who attended the picnic =46
Y = Number of persons at the picnic = 75
Then, the attack rate for gastroenteritis is :
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Example
Secondary Attack Rate
 A secondary attack rate is a measure of the
frequency of new cases of a disease among the
contacts of known cases/primary case.
 The formula is as follows:-
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EXAMPLE
 To calculate the total number of household
contacts, we usually subtract the number of
primary cases from the total number of people
residing in those households.
 Seven(7) cases of hepatitis A occurred among
70 children attending a child care centre.
 Each infected child came from a different
family. The total number of persons in the 7
affected families was 32.
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o One incubation period later, 5 family
members of the 7 infected children also
developed hepatitis A.
o Calculate the attack rate in the child care
centre and the secondary attack rate
among family contacts of those cases?.
o Attack rate in child care centre:
x = cases of hepatitis A among children in
child care center = 7
y = number of children enrolled in the child
care centre = 70
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Figure 3.4
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Mortality Measures
Mortality Rates:-
 A mortality rate is a measure of the frequency
of occurrence of death in a defined population
during a specified interval. For a defined
population, over a specified period of time.
 The following are frequently used mortality
measures,
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Case-fatality rate
 The case-fatality rate is the proportion of persons
with a particular condition (cases) who die from that
condition.
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 Proportionate mortality describes the proportion
of deaths in a specified population over a period of
time attributable to different causes. Each cause is
expressed as a percentage of all deaths, and the sum
of the causes must add to 100%.
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Proportionate mortality Ratio
CDR = No. of deaths in a year x 1000
Total mid-year population
= Hard to use to compare different
populations, due to distortions by
differences in age-sex composition
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Crude Death Rate (CDR):
Age Specific Death Rate
ASDR = total Deaths of at ages a or age group a *
1000
Mid year population at age a or age
group a
Distinguishes the mortality level of different age,
sex, or occupational groups.
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Specific death rate
Cause Specific death rate (CSDR)
 CSDR = Total deaths from a given cause * 1000
population at risk
.
 Infant Mortality Rate (IMR)
IMR = No. of deaths of under 1 in a year x
1000
Live births in a year
= 52 death from 1000 live birth , 2011
EDHS
 Early Neonatal M. R
Deaths under1 week x 1000
Live births
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 Late Neonatal MR:
Deaths 1-4 weeks x 1000
Live births
 Post Neonatal MR :
Deaths 4-52 weeks x 1000
Live births
IMR = ENMR+LNMR+PNMR
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 Child Mortality Rate:
CMR = deaths of children in 1-4 years age
group*1000
Mid-year population of children 1-4
years
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 Under five mortality rate : the
probability of dying between birth & age
five per 1000 live births.
U5MR= No. of deaths of under five children* 1000
total live births
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Maternal Mortality
 Definition:-
A maternal death :- the death of a woman while
pregnant or Within 42 days of termination of
pregnancy, irrespective of the duration and the site
of the pregnancy, from any cause related to or
aggravated by the pregnancy (WHO 1993).
- requires specific cause of death information
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 Maternal Mortality Ratio (MMR) :
MMR = No. of maternal deaths in a year *
100,000
No. of Live births
Example, Eth 2005 ;- 673/100,000 live births
 Represents the risk associated with each
pregnancy, i.e., the obstetric risk
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Maternal mortality measures…
 Maternal Mortality Rate :
= No. of maternal deaths in a specified
period*1000
No. of women of reproductive age
 Represents both the obstetric risk and the
frequency with which women are exposed to
this risk
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Natality Frequency Measures
 Natality measures are used in the area of maternal
and child health and less so in other areas. The
following Table shows a summary for some frequently
used measures of natality.
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Class work
 A total of 2,123,323 deaths were
recorded in the United States in 1987.
The mid-year population was estimated
to be 243,401,000. HIV-related mortality
and population data by age for all
residents and for black males are shown
in Table 2.9. We will use these data to
calculate and interpret the following
four mortality rates:
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 a. Crude mortality rate.
 b. HIV-(cause)-specific mortality rate for
the entire population
 c. HIV-specific mortality among 35- to
44-year-olds
 d. HIV-specific mortality among 35- to
44-year-old black males
Prepared by Mengistu H(MPHE) 65
Answer
A. 872.4 deaths per 100,000 populations
B. 5.5 HIV related death per 100, 000
C. 14.0 HIV related death per 100,000 35-
44years old
D. 72.9 HIV related death per 100,000 35-
44 years old black male
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Relative Risk, Odds Ratio,
Measure of Association
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Measurement of risk:
 A number N of subjects exposed to a factor of
risk for a period of time T. The risk of
becoming ill is the proportion of people in this
cohort of N people, becoming ill (new cases)
during the period T.
Risk (R) = number with the event
Number observed
The risk is therefore a proportion, its minimum
value is zero and its maximum value is 1.
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Testing and measuring the association between
risk factor and diseases
a b a+b
c+d
c d
a+c b+d a+b+c+d
Disease
Yes No
Exposed
No
yes
Total
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Relative risk
 The Relative risk estimates the magnitude of
an association between exposure and disease
and indicates the likelihood of developing the
disease in the exposed group relative to those
who are not exposed.
Risk in exposed = a/a+b
Risk in non-exposed=c/c+d
Therefore, RR = a/a+b
c/c+d
 When the risk in the exposed and the risk in the
non exposed is known, the ratio of these risks
can be calculated and represent the relative
risk. 70
Relative Risk (RR) =Risk in the
exposed
Risk in the non
exposed
 Interpretation :The value of the RR
reflects the magnitude of the
association between exposure and
disease. A relative risk of 5 means that
the probability to develop the disease
in the exposed is 5 times the
probability to develop it in the non
exposed.
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Use of the Relative Risk
 The relative risk measures whether there is
an association between the risk factor and
the frequency of the disease.
 It is a first step into evaluating a causal
relationship. On its own a relative risk
does not allow to conclude about
causality. It only shows an association that
may not be causal.
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a. RR=1 There is no association between exposure
and disease. That means the risk of developing
disease in the exposed and non-exposed groups
are identical.
b. RR>1 There is an association between exposure
and disease and the exposure is associated with an
increase of the frequency of the disease.
c. RR<1 There is an association between exposure
and disease and the exposure is associated with a
decrease of the frequency of the disease
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Calculation of the relative risk
Example :
 A cohort study was carried to examine the effect of
early weaning on diarrhoea. 120 children aged 6
months who were already weaned (exposed) were
compared to 480 control, of the same age, still on
breast milk (non exposed, 4 controls per case).
 The two cohorts were followed up for three months
and any episode of diarrhoea was recorded. Once a
child had had one episode of diarrhoea, she/he was
withdrawn from the study and the risk was then
calculated.
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Interpretation #1: risk in Weaning early is 1.12
times higher than not weaning early
interpretation #2: children who were weaned
early had 1.12 times higher risk of developing
diarrhea when compared to not weaned early .
 Risk in the exposed =
89/120 = 0.74
 Risk in the non exposed =
318/480 = 0.66
 Relative risk = 0.74/0.66 =
1.12
 This is not substantially
different from 1, there is
therefore no association
between early weaning
and diarrhoea, which can
be interpreted as: Breast
milk does not protect
from diarrhoea.
89 31 120
480
318 162
407 193 600
Wean
ed
early
Not
weaned
early
Diarrhoea no diarrhoea
Prepared Mengistu Handiso(MPHE) 75
Odds ratio
 The word "odds" means the chances of an event to
happen.
 The Odds of an event is the ratio of the event to
happen over the event not to happen.
 If a is the number of event happening and b the
number of event not happening, the odds are a/b.
Thus odds= Number with events
Number without events
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 The risk of becoming ill cannot be
calculated in a case control study, the
odds of being ill can be. If in the cohort
study the risk of becoming ill was
a/(a+b), the odds of being ill versus not
being ill is a/b in exposed .
 The ratio of the odds in the exposed
over the odds in the non exposed is
called the Odds Ratio and can be
calculated.
 Again to the prototype two-by-two table
can be used to calculate the odds ratio.
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Calculation of the Odds Ratio
 Odds of being ill in exposed=__a__
b
 Odds of being ill in non exposed = __ c__
d
 Odds ratio (OR) =_Odds in exposed
Odds in non exposed
Odds Ratio = ad/ b c
Prepared Mengistu Handiso(MPHE) 78
Interpretation
 OR=1 There is no association between exposure
and disease. That means the odds of developing
disease in the exposed and non-exposed groups
are identical.
 OR>1 There is an association between exposure
and disease and the exposure is associated with
an increase of the odds of the disease.
 OR<1 There is an association between exposure
and disease and the exposure is associated with a
decrease of the odds of the disease.
Prepared Mengistu Handiso(MPHE) 79
Example
 A case control study of lung cancer and
cigarette smoking was carried out. All the
patients diagnosed to have lung cancer in a
hospital in a certain period of time were
included and their smoking habit recorded.
 For each case (lung cancer) one control (a
patient of same age and sex admitted in
the same hospital, at the same time, for an
other complaint) was chosen and its
smoking habit recorded. The following
table shows the results:
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Interpretation #1
Odds of being ill in smoker is 5.4 times higher than the
Odds of being ill in non smoker.
The odd ratio is: OR=
70x70/30 x 30
= 5.4
 This suggests a fairly
strong association
between smoking
and lung cancer (by
the way the
association is
statistically significant
which means that the
results of this sample
can be extrapolated
to the population as a
whole).
70 30 100
100
30 70
100 100 200
Smokers
Non-
smokers
Lung
cancer
No lung
cancer
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Interpretation #2
• The odd of pt who were current
smoke had 5. 4 times higher risk of
developing lung cancer when
compared to non-smoker.
Impact Measures
82
1. Attributable Risk (AR)
2. Attributable Risk Percent (ARP)
3. Population Attributable Risk (PAR)
4. Population Attributable Risk Percent
(PARP)
Attributable Risk (AR) / Risk
Difference (RD)
83
 AR provides information about the absolute
effect of the exposure or the excess risk of
disease in those exposed.
AR = Incidence among exposed (Ie) _ Incidence among non-
exposed (Io)
 AR quantifies the risk of disease in the exposed
group that is attributable to the exposure by
removing the risk of disease that occurs due to
other causes.
Alternative Naming of AR
84
 Risk difference
 Rate difference
 Cumulative incidence difference
 Incidence density difference
D. Attributable Risk Percent
85
 Estimates the proportion of the disease among
the exposed that is attributable to the
exposure,
 The proportion of the disease in the exposed
group that could be prevented by eliminating
the exposure
AR % = (Ie - Io) X 100
Ie
Example 1
86
 Among 2390 women aged 16 to 49 years
who were free from bacteriuria, 482 were
OC users at the initial survey in 1973,
while 1908 were not. At a second survey
in 1976, 27 of the OC users had
developed bacteriuria, as had 77 of the
non users. Calculate the measure of
association( RR), AR, AR% and interpret
it.
 Draw epidemiological 2x2 table
 What is study design
 Calculate Measure of association
Example:
87
O
C
U
S
E
Bacteruria
Yes No Total
Yes 27 455 482
No 77 1831 1908
Total 104 2286 2390
88
Cohort study
Calculate RR
RR = Ie = 27
lo [ 482 ] = 1.4
[ 77 ]
1908
 Interpretation: women who used oral
contraceptive had 1.4 times higher risk of
developing bacteruria when compared to
non-users.
89
Example: Refer to example 1 and calculate AR
AR = 27 _ 77
482 1908
=0.0156=1566 per 100,000 OC users
Interpretation: The excess occurrence of
bacteruria among OC users attributable to
their OC use is 1566 per 100,000 OC users
Example:
90
Refer to example 1 and calculate AR%
AR % = (27/482-77/1908)/27/482x100
=1566/105 X 100 =27.96 %
27/482
AR % = Ie –Io/Ie X 100
 Interpretation: If OC use causes bacteruria,
about 28 % of bacteruria among women who
use OC can be attributed to their OC use and
can be eliminated if they did not use oral
contraceptives
POSSIBLE OUTCOMES IN STUDYING THE RELATIONSHIP
91
 No association between exposure and disease
AR=0, OR/RR=1
 Positive association between exposure and
disease (more exposure, more disease)
OR/RR>1, AR>0
 Negative association between exposure and
disease
(more exposure, less disease)
AR<0 (negative), OR/ RR <1(fraction, mean
decimal )
Evaluation of causation
Should I believe my
measurement ?
Prepared by Mengistu H(MPHE) 92
Smoking Lung cancer
Associated
OR = 9.1
Due to,
-Chance?
-Confounding?
-Bias?
True association
may be:
-causal
-non-causal
93
Judging Observed Association
Apply the criteria and
make judgment of causality
Prepared Mengistu Handiso(MPHE) 94
Could it be due to selection or measurement
bias?
NO
Could it be due to confounding?
NO
Could it be A result of chance?
NO probability
Could it be Causal?
Common Problems in observed
findings
 Inadequacy of the observed sample
 Inappropriate selection of study
subjects
 Inappropriate/unfair data collection
methods
 Comparing unequal
Prepared Mengistu Handiso(MPHE) 95
Accuracy
 Accuracy = Validity + Precision
.Validity= is the finding a reflection of the
truth?
. Precision= is the finding due to sampling
variation?
Prepared Mengistu Handiso(MPHE) 96
 Validity Vs Reliability
Prepared Mengistu Handiso(MPHE) 97
Precision
 Precision in measurement and estimation
corresponds to the reduction of random error.
 Mostly related to sampling variation or
sampling error.
Solution:
 Increase sample size
 Improving the efficiency of measurement
Prepared Mengistu Handiso(MPHE) 98
Validity
 Internal: are we measuring what we intend to
measure
 Do we have alternative explanations for the
observed findings:
 Chance
 Bias
 Confounding
 External (generalizability) : can we make
inferences beyond the subjects of the study
Prepared Mengistu Handiso(MPHE) 99
Chance/random error
››.››reduced by increasing sample size
 Chance can often be an alternative explanation
to observed findings must always be
considered.
 Evaluation of chance is a domain of statistics
involving:
1. Hypothesis Testing (Test of Statistical
Significance)
2. Estimation of Confidence Interval
 But , Statistical significance do not provide
Prepared Mengistu Handiso(MPHE) 100
P-value ≤ 0.05 􀃆 Chance is unlikely
explanation
 ∴ Reject the null hypothesis
 ∴ There is Statistically significant
difference
Confidence Interval
 Provide information that p-value gives.
– If null value is included in a 95%
confidence interval, by definition the
corresponding P-value is >0.05. so , it is 101
Definition of bias
Any systematic error in an epidemiological
study, that results in an incorrect estimate of the
association between exposure and risk of disease
An alternative explanation for an observed
association is the possibility that some aspect of
the design or conduct of a study has introduced
a bias into the results.
Prepared Mengistu Handiso(MPHE) 102
Bias
 Unlike “chance” and “confounding,” which can be
evaluated quantitatively, the effects of bias are far
more difficult to evaluate and may even be
impossible to take into account in the analysis.
General class of
Bias
Selection Observation
bias (Information)
bias
Prepared Mengistu Handiso(MPHE) 103
Observation/Information Bias
 Results from systematic differences in
the way data on exposure or outcome
are obtained from the various study
groups
››››››››› data collection ?
Prepared Mengistu Handiso(MPHE) 104
Recall Bias
 Sick individuals more likely to remember
and report exposures than healthy
individuals
 Problematic in case-control studies
Prepared Mengistu Handiso(MPHE) 105
Control of Bias in the Design
Phase
1. Choice of Study Population-to reduce
selection bias
2. Data Collection Methods- to reduce
Observation bias
 Use standardized questionnaires
 Train data collectors/interviewers
 Method of data collection should be
similar for all study groups
Prepared Mengistu Handiso(MPHE) 106
A mixing of the effect of the exposure
under study on the disease with that of a
third factor
• A factor which is associated with the
exposure variable, and independent
of the exposure, is related to the
outcome/disease (that is, it’s a risk
Confounding
Prepared Mengistu Handiso(MPHE) 107
Criteria of confounder variable
 It must not intermediate
 It should be risk factor/cause for outcome/
disease with other main variable
 It must be risk for the outcome/disease
independently
Eg
 Coffee and acute MI
 Low density lipoprotein and MI
Prepared Mengistu Handiso(MPHE) 108
Interrelationship
EXPOSURE(A) DISEASE
OR crude ≠ ORA = ORB
CONFOUNDING FACTOR(B)
Prepared Mengistu Handiso(MPHE) 109
Causation
 Epidemiology and statistics review
 Epidemiological concepts of
 disease incidence and prevalence
 relative risk
 Statistical concepts of
 p-values
 confidence intervals
 Epidemiological study designs
 Randomized controlled trials
 Cohort studies
 Case-control studies
 Cross-sectional studies
 Randomized studies tend to offer stronger evidence than
observational studies
Prepared Mengistu Handiso(MPHE) 110
Sir Austin Bradford Hill
 In 1965
 Proceedings of the Royal Society of Medicine
 Bradford Hill’s listed the following criteria in causality
in attempting to distinguish causal and non-causal
associations
1. Strength of association
2. Consistency of findings
3. Biological gradient (dose-response)
4. Temporal sequence
5. Biological plausibility
6. Coherence with established facts
7. Specificity of association
Prepared Mengistu Handiso(MPHE) 111
Strength of the Association
 The Stronger the association (OR
0.00 or + ∞ ), then less likely the
relationship is totally due to the effect of an
uncontrolled confounding variable
 A strong association serves only to rule out
hypothesis that association is entirely due
to weak unmeasured confounder or other
sources of bias
 But weak association does not rule out a
causal association
Prepared Mengistu Handiso(MPHE) 112
Biological Credibility / Plausibility
 The belief in the existence of a cause and
effect relationship is enhanced if there is a
known or postulated biologic mechanism
by which the exposure might reasonably
alter the risk of developing the disease
 Alcohol and CHD (HDL)
 OC use and circulatory disease (platelet
adhesiveness; arterial wall changes)
 Smoking and lung cancer (hundreds of
carcinogens and promoters)
Prepared Mengistu Handiso(MPHE) 113
 Since what is considered biologically
plausible at any given time depends on
the current state of knowledge, the lack
of a known or postulated mechanism
does not necessarily mean that a
particular association is not causal
Prepared by Mengistu H(MPHE) 114
Consistency with Other
Investigations
 Have multiple studies conducted by
multiple investigators concluded the
same thing?
 Relationships that are demonstrated in
multiple studies are more likely to be
causal, i.e., consistent results are found
 in different populations,
 in different circumstances, and
 with different study designs.
Prepared Mengistu Handiso(MPHE) 115
Time Sequence / Temporality
 Exposure of interest has to precede the
outcome (by a period of time that
biologically makes sense)
 Smoking and lung ca; induction/latency
Prepared Mengistu Handiso(MPHE) 116
Dose-Response
 Smoke more, higher CHD death rates
 Difficulty: The presence of a dose-response
relationship doesn’t mean that the association is one
of cause and effect. Could be, for example, due to
confounding.
 Smoking and hepatic cirrhosis (alcohol)
 Absence of a dose-response relationship does not
mean that a cause-effect relationship does not exist.
 Sometimes there is a convincing association but not a
dose-response relationship
Prepared Mengistu Handiso(MPHE) 117
Coherence
 Causal mechanism proposed must not
contradict what is known about the
natural history and biology of the
disease, but the causal relationship may
be indirect data may not be available to
directly support the proposed
mechanism
Prepared Mengistu Handiso(MPHE) 118
Thank you !!
119
Prepared by Mengistu H(MPHE)

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Epide chap 4.pptx epidemology assignment year one

  • 1. Measurement in Epidemiology By Mengistu Handiso (MPHE) Prepared by Mengistu H(MPHE) 1
  • 2. Outline  Epidemiological measurement variables  Measurement of disease occurrence in population  Mortality measures  Measurement of association  Evaluation of causation Prepared by Mengistu H(MPHE) 2
  • 3. Measurement in Epidemiology  Epidemiology is mainly a quantitative discipline, so we should quantify health and health related events.  Epidemiological measurement variables  Absolute number  Ratio  Proportion  Rate Prepared by Mengistu H(MPHE) 3
  • 4.  Measurement of disease occurrence in population 1. Incidence rate  Cumulative Incidence  incidence Density 2. Prevalence rate  Point Prevalence  Period Prevalence  Measurement of mortality (death rate )  Measurement of association 1. Risk ratio 2. Odd ratio, 3. Risk difference Prepared by Mengistu H(MPHE) 4
  • 5. Measuring Disease Occurrence Absolute number  The number of cases(Absolute number ) in a given community can give more epidemiologic sense if they are related to the size of the population.  Such tie of the number of cases with the population size can be determined by calculating ratios, proportions, and rates Prepared by Mengistu H(MPHE) 5
  • 6. Ratio x፡y  Ratio: The value of x and y may be completely independent. example (Male: Female) Proportion x/ x+y  Proportion: is a ratio (expressed as a percent) in which x is included in y.  Example Female/Both sexes (proportion of female in a community) Prepared by Mengistu H(MPHE) 6
  • 7. Rate  Rate is a Proportion, it measures the occurrence of an event in a population over time.  The time component is important in the definition. Measles cases in under five children in 1995 Under five children in 1995 Prepared by Mengistu H(MPHE) 7
  • 8.  Notice three important aspects of this formula. 1. The persons in the denominator must reflect the population from which the cases in the numerator arose. 2. The counts in the numerator and denominator should cover the same time period. 3. In theory, the persons in the denominator must be “at risk” for the event, that is, it should have been possible for them to experience the event Prepared by Mengistu H(MPHE) 8
  • 9. Table1.1 Neonatal sepsis, Hospital A, Ethiopia, 2003 Prepared by Mengistu H(MPHE) 9
  • 10. The line listing in the Table 1.1 presents some of the information collected on infants born at Hospital A with neonatal sepsis. 1. What is the ratio of males to females? 2. What proportion of infants lived? 3. What proportion of infants were delivered in a delivery room? 4. What is the ratio of operating room deliveries to delivery room deliveries? Prepared by Mengistu H(MPHE) 10
  • 11. Incidence rate  Incidence rates are the most common way of measuring and comparing the frequency of disease in populations.  It measures the rate at which people without the disease develop the disease during a specified period of time.  The incidence rate expresses the probability or risk of illness in a population over a period of time. Prepared by Mengistu H(MPHE) 11
  • 12.  Since incidence is a measure of risk, when one population has a higher incidence of disease than another, we say that the first population is at a higher risk of developing disease than the second, all other factors being equal. Prepared by Mengistu H(MPHE) 12
  • 13.  It is used to study disease aetiology  Required data:  period of observation;( Time)  number of new cases; (n)  time of disease onset (diagnosis Time );  population at risk /denominator(N).  The formula for calculating an incidence rate follows: Prepared by Mengistu H(MPHE) 13
  • 14.  The numerator of an incidence rate should reflect new cases of disease which occurred or were diagnosed during the specified period.  The denominator is the population at risk.  This means that persons who are included in the denominator should be able to develop the disease that is being described during the time period covered. Prepared by Mengistu H(MPHE) 14
  • 15. Risk (Cumulative Incidence)  Measures the risk (the likelihood, probability) that an individual will contract the disease during a certain time period or before a given age. = New cases occurring during a given time period Population at risk during the same period  Cumulative incidence relates occurrences of new cases to the population at the beginning of the study period. Prepared by Mengistu H(MPHE) 15
  • 16. Example  Two surveys were done of the same community 12 months apart. Of 5,000 people surveyed the first time, 25 had antibodies to histoplasmosis.  Twelve months later, 35 had antibodies, including the original 25. 1. What is cumulative/ Incidence during the 12-month period: x = Number of new positives during the 12-month period = 35 - 25 = 10 y = population at risk = 5,000 - 25 = 4,975 x/y . 10n = 10/4,975 x1,000 = 2 per 1,000 2. Prevalence at the second survey: x = antibody positive at second survey = 35 y = population = 5,000 n Prepared by Mengistu H(MPHE) 16
  • 17. Incidence Density  Incidence density represents rate at which new cases are occurring.  Does not indicate the risk for any individual in a population. = New cases occurring in a specified period Total person-time at risk in the same period  An incidence measure is a speed, usually expressed as number of cases per 1,000 or 100,000 units of follow-up time Prepared by Mengistu H(MPHE) 17
  • 18.  The population at risk is dynamic and each person in the population contributes the amount of time that they remained under observation and free from disease (person-time)  The numerator is still the number of new cases, but the denominator is the sum of the time each person is observed, totalled for all persons. Prepared by Mengistu H(MPHE) 18
  • 19.  Person-time rates are often used in cohort (follow-up) studies of diseases with long incubation or latency periods, such as occupationally related diseases, AIDS, and chronic diseases.  Time unit=month, year, day  person-time=person-year, person- month, Prepared by Mengistu H(MPHE) 19
  • 20. Example:-  Investigators enrolled 2,100 men in a study and followed them over 4 years to determine the rate of heart disease.  We assume that persons diagnosed with disease and those lost to follow-up were disease-free for half of the year, and thus contribute ½ year to the denominator. Prepared by Mengistu H(MPHE) 20
  • 21. Example  Initial enrolment: 2,100 men free of disease  After 1 year: 2,000 disease-free, 0 with disease, 100 lost to follow-up  After 2 years: 1,900 disease-free, 1 with disease, 99 lost to follow-up  After 3 years: 1,100 disease-free, 7 with disease, 793 lost to follow-up  After 4 years: 700 disease-free, 8 with disease, 392 lost to follow-up 1. Identify x: x = cases diagnosed = 1 + 7 + 8 = 16 2. Calculate y, the person-years of observation Prepared by Mengistu H(MPHE) 21
  • 22.  700 men x 4.0 years = 2,800 person-years  8 + 392 = 400 menx3.5 years = 1,400 person- years  7 + 793 = 800 menx2.5 years = 2,000 person- years  1 + 99 = 100 menx1.5 years = 150 person-years  0 + 100 = 100 menx0.5 years = 50 person-years  Total = 6,400 person-years of observation Prepared by Mengistu H(MPHE) 22
  • 23. Prepared by Mengistu H(MPHE) 23
  • 24. Prevalence rate  Prevalence, sometimes referred to as prevalence rate, is the proportion of persons in a population who have a particular disease or attribute at a specified point in time or over a specified period of time.  Numerator is number of existing cases  Denominator is your population of interest (including all those in numerator)  The formula for presence of disease is: Prepared by Mengistu H(MPHE) 24
  • 25. Prepared by Mengistu H(MPHE) 25
  • 26. Point prevalence:- Point prevalence is the amount of disease present in a population at a single point in time. Point prevalence = all the cases of factor of interest at a given time x10n total population Prepared by Mengistu H(MPHE) 26
  • 27. Prepared by Mengistu H(MPHE) 27 Period prevalence. The numerator in period prevalence is the number of persons who had a particular disease or attribute at any time during a particular interval (week, month, year, decade, or any other specified time period). Period prevalence = all cases (old and new) of the factor of interest during the time period x 10n average population during the given period of time
  • 28. Exercise 2.4  Recall that Figure 2.1 represents ten episodes of an illness in a population of 20 over a period of 16 months.  Each horizontal line represents the portion of time one person spends being ill. The line begins on the date of onset and ends on the date of death or recovery. 28 Prepared by Mengistu H(MPHE)
  • 30. Calculate the following rates: a. Point prevalence on October 1, 1990 b. Period prevalence, October 1, 1990 to September 30, 1991 C, point prevalence on September 30,1991 30 Prepared by Mengistu H(MPHE)
  • 31. a. Point prevalence on October 1, 1990: x = cases present on 10/1/90 = 6 y = population = 20 = x /y .10n= 6/20 × 100 = 30% 31 Prepared by Mengistu H(MPHE)
  • 32. b. Period prevalence, October 1, 1990 to September 30, 1991 x = cases present between 10/1/90 and 9/30/91 = 6 old case , 4 new case =10 y = population = 20 x/y × 10n =  10 /20× 100 = 50% 32 Prepared by Mengistu H(MPHE)
  • 33. C, point prevalence rate on September 30,1991 x= 6 old case, 4 new case , 5 death x/y =6+4-5/20 = 5/20*100 = 25% 33 Prepared by Mengistu H(MPHE)
  • 34. Calculation : in f/up {cohort study ) Incidence rate;-  Subtract old case from denominator(risk )  Subtract dead, cure case from the numerator=new case=point type) Point Prevalence rate :-  Subtract dead, cure case from the numerator = (old &new case )=point prevalence 34 Prepared by Mengistu H(MPHE)
  • 35. In a study population of 1000 inhabitants there are 60 cases of tuberculosis and 20 cases of hypertension. During the first six months there are 17 new cases of tuberculosis and 8 new cases of hypertension. At the end of the year the total of new cases is 27 for tuberculosis and 13 for hypertension. During the same period, 8 new cases of tuberculosis died and 8 were cured. In the same period, 5 cases of hypertension died and no case of hypertension was cured. Calculate the following rates :- 1. -Prevalence rate at the beginning of the study 2. -Incidence rate A) tuberculosis and B) hypertension at the end of the first six months 3. -Incidence rate of tuberculosis at the end of the year 4. -Prevalence rate of A)tuberculosis and B) hypertension at the end of the year 35 Class work
  • 36. Possible answer Prepared by Mengistu H(MPHE) 36
  • 37. Characteristics of Prevalence Prepared by Mengistu H(MPHE) 37 Cause and effect measured simultaneously -Impossible to infer causation Useful for planning (e.g. beds, clinics, workforce needs) High prevalence  high risk  could reflect increased survival(improved care, behavior change - long duration)/old case Low prevalence  low risk  could reflect rapid fatal or cure process - short duration) Easy to obtain need only one measurement
  • 38. Figure 3.2 Relationship between prevalence and incidence Prepared by Mengistu H(MPHE) 38 Migration Care, behavioral change , -Dx
  • 39. Relationship between prevalence and incidence  Prevalence is based on both incidence (risk) and duration of disease. P ≈ I*D  High prevalence of a disease within a population may reflect high risk, or it may reflect prolonged survival without cure.  Conversely, low prevalence may indicate low incidence, a rapidly fatal process, or rapid recovery. Prepared by Mengistu H(MPHE) 39
  • 40. Comparison of prevalence and incidence  The prevalence and incidence of disease are frequently confused.  They are similar, but differ in what cases are included in the numerator.  Numerator of Incidence = new cases occurring during a given time period  Numerator of Prevalence = all cases present during a given time period  As you can see, the numerator of an incidence rate consists only of persons whose illness began during a specified interval. Prepared by Mengistu H(MPHE) 40
  • 41. Prevalence rate increased by •Longer duration of the disease •Prolongation of life of patients without cure. •Increase in new cases •Immigration of cases •Out migration of health people •In-migration of susceptible people •Improved diagnostic facility Prepared by Mengistu H(MPHE) 41
  • 42. Prevalence rate decreased by •Shorter duration of disease. •High case-fatality rate from disease. •Decreases in new cases (decrease in incidence) •In-migration of healthy people. •Out migration of cases. •Improved cure rate of case Prepared by Mengistu H(MPHE) 42
  • 43. Attack Rate  An attack rate is a variant of an incidence rate, applied to a narrowly defined population observed for a limited time, such as during an epidemic.  The attack rate is usually expressed as a per cent, so 10n equals 100.  For a defined population (the population at risk), during a limited time period. Prepared by Mengistu H(MPHE) 43
  • 44.  Of 75 persons who attended a church picnic, 46 subsequently developed gastroenteritis.  To calculate the attack rate of gastroenteritis we first define the numerator and denominator: X = Cases of gastroenteritis occurring within the incubation period for gastroenteritis among persons who attended the picnic =46 Y = Number of persons at the picnic = 75 Then, the attack rate for gastroenteritis is : Prepared by Mengistu H(MPHE) 44 Example
  • 45. Secondary Attack Rate  A secondary attack rate is a measure of the frequency of new cases of a disease among the contacts of known cases/primary case.  The formula is as follows:- Prepared by Mengistu H(MPHE) 45
  • 46. EXAMPLE  To calculate the total number of household contacts, we usually subtract the number of primary cases from the total number of people residing in those households.  Seven(7) cases of hepatitis A occurred among 70 children attending a child care centre.  Each infected child came from a different family. The total number of persons in the 7 affected families was 32. Prepared by Mengistu H(MPHE) 46
  • 47. o One incubation period later, 5 family members of the 7 infected children also developed hepatitis A. o Calculate the attack rate in the child care centre and the secondary attack rate among family contacts of those cases?. o Attack rate in child care centre: x = cases of hepatitis A among children in child care center = 7 y = number of children enrolled in the child care centre = 70 Prepared by Mengistu H(MPHE) 47
  • 48. Figure 3.4 Prepared by Mengistu H(MPHE) 48
  • 49. Prepared by Mengistu H(MPHE) 49
  • 50. Mortality Measures Mortality Rates:-  A mortality rate is a measure of the frequency of occurrence of death in a defined population during a specified interval. For a defined population, over a specified period of time.  The following are frequently used mortality measures, Prepared by Mengistu H(MPHE) 50
  • 51. Case-fatality rate  The case-fatality rate is the proportion of persons with a particular condition (cases) who die from that condition. Prepared by Mengistu H(MPHE) 51
  • 52.  Proportionate mortality describes the proportion of deaths in a specified population over a period of time attributable to different causes. Each cause is expressed as a percentage of all deaths, and the sum of the causes must add to 100%. Prepared by Mengistu H(MPHE) 52 Proportionate mortality Ratio
  • 53. CDR = No. of deaths in a year x 1000 Total mid-year population = Hard to use to compare different populations, due to distortions by differences in age-sex composition Prepared by Mengistu H(MPHE) 53 Crude Death Rate (CDR):
  • 54. Age Specific Death Rate ASDR = total Deaths of at ages a or age group a * 1000 Mid year population at age a or age group a Distinguishes the mortality level of different age, sex, or occupational groups. Prepared by Mengistu H(MPHE) 54 Specific death rate Cause Specific death rate (CSDR)  CSDR = Total deaths from a given cause * 1000 population at risk .
  • 55.  Infant Mortality Rate (IMR) IMR = No. of deaths of under 1 in a year x 1000 Live births in a year = 52 death from 1000 live birth , 2011 EDHS  Early Neonatal M. R Deaths under1 week x 1000 Live births Prepared by Mengistu H(MPHE) 55
  • 56.  Late Neonatal MR: Deaths 1-4 weeks x 1000 Live births  Post Neonatal MR : Deaths 4-52 weeks x 1000 Live births IMR = ENMR+LNMR+PNMR Prepared by Mengistu H(MPHE) 56
  • 57.  Child Mortality Rate: CMR = deaths of children in 1-4 years age group*1000 Mid-year population of children 1-4 years Prepared by Mengistu H(MPHE) 57
  • 58.  Under five mortality rate : the probability of dying between birth & age five per 1000 live births. U5MR= No. of deaths of under five children* 1000 total live births 58 Prepared by Mengistu H(MPHE)
  • 59. Maternal Mortality  Definition:- A maternal death :- the death of a woman while pregnant or Within 42 days of termination of pregnancy, irrespective of the duration and the site of the pregnancy, from any cause related to or aggravated by the pregnancy (WHO 1993). - requires specific cause of death information Prepared by Mengistu H(MPHE) 59
  • 60.  Maternal Mortality Ratio (MMR) : MMR = No. of maternal deaths in a year * 100,000 No. of Live births Example, Eth 2005 ;- 673/100,000 live births  Represents the risk associated with each pregnancy, i.e., the obstetric risk Prepared by Mengistu H(MPHE) 60
  • 61. Maternal mortality measures…  Maternal Mortality Rate : = No. of maternal deaths in a specified period*1000 No. of women of reproductive age  Represents both the obstetric risk and the frequency with which women are exposed to this risk Prepared by Mengistu H(MPHE) 61
  • 62. Natality Frequency Measures  Natality measures are used in the area of maternal and child health and less so in other areas. The following Table shows a summary for some frequently used measures of natality. Prepared by Mengistu H(MPHE) 62
  • 63. Class work  A total of 2,123,323 deaths were recorded in the United States in 1987. The mid-year population was estimated to be 243,401,000. HIV-related mortality and population data by age for all residents and for black males are shown in Table 2.9. We will use these data to calculate and interpret the following four mortality rates: Prepared by Mengistu H(MPHE) 63
  • 64. Prepared by Mengistu H(MPHE) 64
  • 65.  a. Crude mortality rate.  b. HIV-(cause)-specific mortality rate for the entire population  c. HIV-specific mortality among 35- to 44-year-olds  d. HIV-specific mortality among 35- to 44-year-old black males Prepared by Mengistu H(MPHE) 65
  • 66. Answer A. 872.4 deaths per 100,000 populations B. 5.5 HIV related death per 100, 000 C. 14.0 HIV related death per 100,000 35- 44years old D. 72.9 HIV related death per 100,000 35- 44 years old black male Prepared by Mengistu H(MPHE) 66
  • 67. Relative Risk, Odds Ratio, Measure of Association Prepared Mengistu Handiso(MPHE) 67
  • 68. Measurement of risk:  A number N of subjects exposed to a factor of risk for a period of time T. The risk of becoming ill is the proportion of people in this cohort of N people, becoming ill (new cases) during the period T. Risk (R) = number with the event Number observed The risk is therefore a proportion, its minimum value is zero and its maximum value is 1. Prepared Mengistu Handiso(MPHE) 68
  • 69. Testing and measuring the association between risk factor and diseases a b a+b c+d c d a+c b+d a+b+c+d Disease Yes No Exposed No yes Total Prepared Mengistu Handiso(MPHE) 69
  • 70. Relative risk  The Relative risk estimates the magnitude of an association between exposure and disease and indicates the likelihood of developing the disease in the exposed group relative to those who are not exposed. Risk in exposed = a/a+b Risk in non-exposed=c/c+d Therefore, RR = a/a+b c/c+d  When the risk in the exposed and the risk in the non exposed is known, the ratio of these risks can be calculated and represent the relative risk. 70
  • 71. Relative Risk (RR) =Risk in the exposed Risk in the non exposed  Interpretation :The value of the RR reflects the magnitude of the association between exposure and disease. A relative risk of 5 means that the probability to develop the disease in the exposed is 5 times the probability to develop it in the non exposed. Prepared Mengistu Handiso(MPHE) 71
  • 72. Use of the Relative Risk  The relative risk measures whether there is an association between the risk factor and the frequency of the disease.  It is a first step into evaluating a causal relationship. On its own a relative risk does not allow to conclude about causality. It only shows an association that may not be causal. Prepared Mengistu Handiso(MPHE) 72
  • 73. a. RR=1 There is no association between exposure and disease. That means the risk of developing disease in the exposed and non-exposed groups are identical. b. RR>1 There is an association between exposure and disease and the exposure is associated with an increase of the frequency of the disease. c. RR<1 There is an association between exposure and disease and the exposure is associated with a decrease of the frequency of the disease Prepared Mengistu Handiso(MPHE) 73
  • 74. Calculation of the relative risk Example :  A cohort study was carried to examine the effect of early weaning on diarrhoea. 120 children aged 6 months who were already weaned (exposed) were compared to 480 control, of the same age, still on breast milk (non exposed, 4 controls per case).  The two cohorts were followed up for three months and any episode of diarrhoea was recorded. Once a child had had one episode of diarrhoea, she/he was withdrawn from the study and the risk was then calculated. Prepared Mengistu Handiso(MPHE) 74
  • 75. Interpretation #1: risk in Weaning early is 1.12 times higher than not weaning early interpretation #2: children who were weaned early had 1.12 times higher risk of developing diarrhea when compared to not weaned early .  Risk in the exposed = 89/120 = 0.74  Risk in the non exposed = 318/480 = 0.66  Relative risk = 0.74/0.66 = 1.12  This is not substantially different from 1, there is therefore no association between early weaning and diarrhoea, which can be interpreted as: Breast milk does not protect from diarrhoea. 89 31 120 480 318 162 407 193 600 Wean ed early Not weaned early Diarrhoea no diarrhoea Prepared Mengistu Handiso(MPHE) 75
  • 76. Odds ratio  The word "odds" means the chances of an event to happen.  The Odds of an event is the ratio of the event to happen over the event not to happen.  If a is the number of event happening and b the number of event not happening, the odds are a/b. Thus odds= Number with events Number without events Prepared Mengistu Handiso(MPHE) 76
  • 77.  The risk of becoming ill cannot be calculated in a case control study, the odds of being ill can be. If in the cohort study the risk of becoming ill was a/(a+b), the odds of being ill versus not being ill is a/b in exposed .  The ratio of the odds in the exposed over the odds in the non exposed is called the Odds Ratio and can be calculated.  Again to the prototype two-by-two table can be used to calculate the odds ratio. Prepared Mengistu Handiso(MPHE) 77
  • 78. Calculation of the Odds Ratio  Odds of being ill in exposed=__a__ b  Odds of being ill in non exposed = __ c__ d  Odds ratio (OR) =_Odds in exposed Odds in non exposed Odds Ratio = ad/ b c Prepared Mengistu Handiso(MPHE) 78
  • 79. Interpretation  OR=1 There is no association between exposure and disease. That means the odds of developing disease in the exposed and non-exposed groups are identical.  OR>1 There is an association between exposure and disease and the exposure is associated with an increase of the odds of the disease.  OR<1 There is an association between exposure and disease and the exposure is associated with a decrease of the odds of the disease. Prepared Mengistu Handiso(MPHE) 79
  • 80. Example  A case control study of lung cancer and cigarette smoking was carried out. All the patients diagnosed to have lung cancer in a hospital in a certain period of time were included and their smoking habit recorded.  For each case (lung cancer) one control (a patient of same age and sex admitted in the same hospital, at the same time, for an other complaint) was chosen and its smoking habit recorded. The following table shows the results: Prepared Mengistu Handiso(MPHE) 80
  • 81. Interpretation #1 Odds of being ill in smoker is 5.4 times higher than the Odds of being ill in non smoker. The odd ratio is: OR= 70x70/30 x 30 = 5.4  This suggests a fairly strong association between smoking and lung cancer (by the way the association is statistically significant which means that the results of this sample can be extrapolated to the population as a whole). 70 30 100 100 30 70 100 100 200 Smokers Non- smokers Lung cancer No lung cancer Prepared Mengistu Handiso(MPHE) 81 Interpretation #2 • The odd of pt who were current smoke had 5. 4 times higher risk of developing lung cancer when compared to non-smoker.
  • 82. Impact Measures 82 1. Attributable Risk (AR) 2. Attributable Risk Percent (ARP) 3. Population Attributable Risk (PAR) 4. Population Attributable Risk Percent (PARP)
  • 83. Attributable Risk (AR) / Risk Difference (RD) 83  AR provides information about the absolute effect of the exposure or the excess risk of disease in those exposed. AR = Incidence among exposed (Ie) _ Incidence among non- exposed (Io)  AR quantifies the risk of disease in the exposed group that is attributable to the exposure by removing the risk of disease that occurs due to other causes.
  • 84. Alternative Naming of AR 84  Risk difference  Rate difference  Cumulative incidence difference  Incidence density difference
  • 85. D. Attributable Risk Percent 85  Estimates the proportion of the disease among the exposed that is attributable to the exposure,  The proportion of the disease in the exposed group that could be prevented by eliminating the exposure AR % = (Ie - Io) X 100 Ie
  • 86. Example 1 86  Among 2390 women aged 16 to 49 years who were free from bacteriuria, 482 were OC users at the initial survey in 1973, while 1908 were not. At a second survey in 1976, 27 of the OC users had developed bacteriuria, as had 77 of the non users. Calculate the measure of association( RR), AR, AR% and interpret it.  Draw epidemiological 2x2 table  What is study design  Calculate Measure of association
  • 87. Example: 87 O C U S E Bacteruria Yes No Total Yes 27 455 482 No 77 1831 1908 Total 104 2286 2390
  • 88. 88 Cohort study Calculate RR RR = Ie = 27 lo [ 482 ] = 1.4 [ 77 ] 1908  Interpretation: women who used oral contraceptive had 1.4 times higher risk of developing bacteruria when compared to non-users.
  • 89. 89 Example: Refer to example 1 and calculate AR AR = 27 _ 77 482 1908 =0.0156=1566 per 100,000 OC users Interpretation: The excess occurrence of bacteruria among OC users attributable to their OC use is 1566 per 100,000 OC users
  • 90. Example: 90 Refer to example 1 and calculate AR% AR % = (27/482-77/1908)/27/482x100 =1566/105 X 100 =27.96 % 27/482 AR % = Ie –Io/Ie X 100  Interpretation: If OC use causes bacteruria, about 28 % of bacteruria among women who use OC can be attributed to their OC use and can be eliminated if they did not use oral contraceptives
  • 91. POSSIBLE OUTCOMES IN STUDYING THE RELATIONSHIP 91  No association between exposure and disease AR=0, OR/RR=1  Positive association between exposure and disease (more exposure, more disease) OR/RR>1, AR>0  Negative association between exposure and disease (more exposure, less disease) AR<0 (negative), OR/ RR <1(fraction, mean decimal )
  • 92. Evaluation of causation Should I believe my measurement ? Prepared by Mengistu H(MPHE) 92
  • 93. Smoking Lung cancer Associated OR = 9.1 Due to, -Chance? -Confounding? -Bias? True association may be: -causal -non-causal 93
  • 94. Judging Observed Association Apply the criteria and make judgment of causality Prepared Mengistu Handiso(MPHE) 94 Could it be due to selection or measurement bias? NO Could it be due to confounding? NO Could it be A result of chance? NO probability Could it be Causal?
  • 95. Common Problems in observed findings  Inadequacy of the observed sample  Inappropriate selection of study subjects  Inappropriate/unfair data collection methods  Comparing unequal Prepared Mengistu Handiso(MPHE) 95
  • 96. Accuracy  Accuracy = Validity + Precision .Validity= is the finding a reflection of the truth? . Precision= is the finding due to sampling variation? Prepared Mengistu Handiso(MPHE) 96
  • 97.  Validity Vs Reliability Prepared Mengistu Handiso(MPHE) 97
  • 98. Precision  Precision in measurement and estimation corresponds to the reduction of random error.  Mostly related to sampling variation or sampling error. Solution:  Increase sample size  Improving the efficiency of measurement Prepared Mengistu Handiso(MPHE) 98
  • 99. Validity  Internal: are we measuring what we intend to measure  Do we have alternative explanations for the observed findings:  Chance  Bias  Confounding  External (generalizability) : can we make inferences beyond the subjects of the study Prepared Mengistu Handiso(MPHE) 99
  • 100. Chance/random error ››.››reduced by increasing sample size  Chance can often be an alternative explanation to observed findings must always be considered.  Evaluation of chance is a domain of statistics involving: 1. Hypothesis Testing (Test of Statistical Significance) 2. Estimation of Confidence Interval  But , Statistical significance do not provide Prepared Mengistu Handiso(MPHE) 100
  • 101. P-value ≤ 0.05 􀃆 Chance is unlikely explanation  ∴ Reject the null hypothesis  ∴ There is Statistically significant difference Confidence Interval  Provide information that p-value gives. – If null value is included in a 95% confidence interval, by definition the corresponding P-value is >0.05. so , it is 101
  • 102. Definition of bias Any systematic error in an epidemiological study, that results in an incorrect estimate of the association between exposure and risk of disease An alternative explanation for an observed association is the possibility that some aspect of the design or conduct of a study has introduced a bias into the results. Prepared Mengistu Handiso(MPHE) 102
  • 103. Bias  Unlike “chance” and “confounding,” which can be evaluated quantitatively, the effects of bias are far more difficult to evaluate and may even be impossible to take into account in the analysis. General class of Bias Selection Observation bias (Information) bias Prepared Mengistu Handiso(MPHE) 103
  • 104. Observation/Information Bias  Results from systematic differences in the way data on exposure or outcome are obtained from the various study groups ››››››››› data collection ? Prepared Mengistu Handiso(MPHE) 104
  • 105. Recall Bias  Sick individuals more likely to remember and report exposures than healthy individuals  Problematic in case-control studies Prepared Mengistu Handiso(MPHE) 105
  • 106. Control of Bias in the Design Phase 1. Choice of Study Population-to reduce selection bias 2. Data Collection Methods- to reduce Observation bias  Use standardized questionnaires  Train data collectors/interviewers  Method of data collection should be similar for all study groups Prepared Mengistu Handiso(MPHE) 106
  • 107. A mixing of the effect of the exposure under study on the disease with that of a third factor • A factor which is associated with the exposure variable, and independent of the exposure, is related to the outcome/disease (that is, it’s a risk Confounding Prepared Mengistu Handiso(MPHE) 107
  • 108. Criteria of confounder variable  It must not intermediate  It should be risk factor/cause for outcome/ disease with other main variable  It must be risk for the outcome/disease independently Eg  Coffee and acute MI  Low density lipoprotein and MI Prepared Mengistu Handiso(MPHE) 108
  • 109. Interrelationship EXPOSURE(A) DISEASE OR crude ≠ ORA = ORB CONFOUNDING FACTOR(B) Prepared Mengistu Handiso(MPHE) 109
  • 110. Causation  Epidemiology and statistics review  Epidemiological concepts of  disease incidence and prevalence  relative risk  Statistical concepts of  p-values  confidence intervals  Epidemiological study designs  Randomized controlled trials  Cohort studies  Case-control studies  Cross-sectional studies  Randomized studies tend to offer stronger evidence than observational studies Prepared Mengistu Handiso(MPHE) 110
  • 111. Sir Austin Bradford Hill  In 1965  Proceedings of the Royal Society of Medicine  Bradford Hill’s listed the following criteria in causality in attempting to distinguish causal and non-causal associations 1. Strength of association 2. Consistency of findings 3. Biological gradient (dose-response) 4. Temporal sequence 5. Biological plausibility 6. Coherence with established facts 7. Specificity of association Prepared Mengistu Handiso(MPHE) 111
  • 112. Strength of the Association  The Stronger the association (OR 0.00 or + ∞ ), then less likely the relationship is totally due to the effect of an uncontrolled confounding variable  A strong association serves only to rule out hypothesis that association is entirely due to weak unmeasured confounder or other sources of bias  But weak association does not rule out a causal association Prepared Mengistu Handiso(MPHE) 112
  • 113. Biological Credibility / Plausibility  The belief in the existence of a cause and effect relationship is enhanced if there is a known or postulated biologic mechanism by which the exposure might reasonably alter the risk of developing the disease  Alcohol and CHD (HDL)  OC use and circulatory disease (platelet adhesiveness; arterial wall changes)  Smoking and lung cancer (hundreds of carcinogens and promoters) Prepared Mengistu Handiso(MPHE) 113
  • 114.  Since what is considered biologically plausible at any given time depends on the current state of knowledge, the lack of a known or postulated mechanism does not necessarily mean that a particular association is not causal Prepared by Mengistu H(MPHE) 114
  • 115. Consistency with Other Investigations  Have multiple studies conducted by multiple investigators concluded the same thing?  Relationships that are demonstrated in multiple studies are more likely to be causal, i.e., consistent results are found  in different populations,  in different circumstances, and  with different study designs. Prepared Mengistu Handiso(MPHE) 115
  • 116. Time Sequence / Temporality  Exposure of interest has to precede the outcome (by a period of time that biologically makes sense)  Smoking and lung ca; induction/latency Prepared Mengistu Handiso(MPHE) 116
  • 117. Dose-Response  Smoke more, higher CHD death rates  Difficulty: The presence of a dose-response relationship doesn’t mean that the association is one of cause and effect. Could be, for example, due to confounding.  Smoking and hepatic cirrhosis (alcohol)  Absence of a dose-response relationship does not mean that a cause-effect relationship does not exist.  Sometimes there is a convincing association but not a dose-response relationship Prepared Mengistu Handiso(MPHE) 117
  • 118. Coherence  Causal mechanism proposed must not contradict what is known about the natural history and biology of the disease, but the causal relationship may be indirect data may not be available to directly support the proposed mechanism Prepared Mengistu Handiso(MPHE) 118
  • 119. Thank you !! 119 Prepared by Mengistu H(MPHE)