EPI-546 Block I

Lecture 3: Frequency

How do we measure disease, define risks, and then

make use of this information?

Mathew J. Reeves BVSc, PhD

Associate Professor, Epidemiology

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Objectives - Concepts
• 1. Understand the concept of uncertainty, probability and
odds

• 2. Measures of disease frequency

• Prevalence
• Incidence
– Cumulative incidence
– Incidence density (the concept of person-time)

• 3. Relationship between incidence, duration &

prevalence

• 4. Risk estimates and their uses

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Objectives - Skills

• 1. Convert probability to odds and vice versa

• 2. Define, calculate and interpret prevalence,

cumulative incidence, and incidence density

• 3. Define, calculate and interpret “risk

estimates”

• RR, RRR, ARR, NNT, OR, PAR, PARF

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Measuring Disease and Defining Risks

• Clinicians are required to know or make estimates of

many things:
• The occurrence of disease in a population
• The “risk” of developing a disease or an outcome (prognosis)
• The risks and benefits of a proposed treatment

• This skill requires an understanding of:

• Measures of disease frequency
– Proportions and odds
– Prevalence and incidence rates
– Risk (relative and absolute)

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Uncertainty
• Medicine isn’t an exact science, uncertainty is ever
present

• Uncertainty can be expressed either:

• Qualitatively using terms like ‘probable’, ‘possible’, ‘unlikely’

– Study: Docs asked to assign prob. to commonly used words:
• ‘Consistent with’ ranged from 0.18-0.98
• ‘Unlikely’ ranged from 0.01 to 0.93

• Quantitatively using probabilities (P)

– Advantage: explicit interpretation, exactness
– Disadvantage: may force one to be more exact that is justified!

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Probability vs. Odds
Probability (P) or “risk” of having an event
Odds = ratio of the probability of having an event to the probability
of not having the event or P / (1 – P)
Example: 1 out of 5 patients suffer a stroke…….

• P = 1/5 = 0.2 or 20%

• Odds = (P) / (1-P)

• Odds = 0.2 / 0.8 or 1:4
or “one to four”

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Relationship between Prob. and odds
Probability and odds are more alike the lower the absolute P (risk)

Probability Odds • Prob = Odds/1 + Odds

0.80 4 • Odds = Prob/1 – Prob
0.67 2
0.60 1.5
0.50 1.0 • Example:
0.40 0.67 Prob = 2/[1 + 2]
0.33 0.5 Prob = 2/3 = 0.67
0.25 0.33
0.20 0.25 Odds= 0.67/[1-0.67]
0.10 0.11 Odds= 0.67/0.33 = 2
0.05 0.053
0.01 0.0101
Mathew J. Reeves, Dept. of
Epidemiology, Mich State Univ.
Measures of disease frequency
- Prevalence
Defn: the proportion of a defined group or population that has a
clinical condition or outcome at a given point in time

• Prev = Number of cases observed at time t

Total number of individuals at time t

– ranges from 0 to 1 (it’s a proportion), but usually referred to as

a rate and is often shown as a %

• Example:
– Of 100 patients hospitalized with stroke, 18 had ICH
– Prevalence of ICH among hospitalized stroke patients = 18%

• The prevalence rate answers the question:

• “what fraction of the group is affected at this moment in
time?”

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Measures of disease frequency
– Incidence Rates
• A special type of proportion that includes a specific
time period and population-at-risk

• Numerator = the number of newly affected individuals

occurring over a specified time period

• Denominator = the population-at-risk over the same

time period

• There are two types of incidence rates……..

Mathew J. Reeves, Dept. of
Epidemiology, Mich State Univ.
Cumulative Incidence Rate (CIR)
Defn: the proportion of a defined at-risk group or population that
develops a new clinical condition or outcome over a given time
period.

• CIR= Num. of newly disease indv. for a specific time period

Total number of population-at-risk for same time period

• Measures the proportion of at-risk individuals who develop a

condition or outcome over a specified time period

• Ranges from 0 to 1 (so it’s a proportion!) but called a rate

because it includes time period and population-at-risk

• Must be accompanied by a specified time period to be

interpretable - because the CIR must increase with time
– 7-day CIR of stroke following TIA = 5%
– 90-day CIR of stroke following TIA = 10%

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Cumulative Incidence of GI side effects for Rofecoxib (VIOXX)
vs. Naproxen - The VIGOR Trial (Bombardier NEJM 2000)

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Cumulative Incidence Rate (CIR)
• A measure of “average risk”
• CIR answers the question: “what is the probability or chance
that an individual develops the outcome over time”

• Also referred to as the “risk” or “event rate”

• Common risks or CIR’s

• 5-year breast cancer survival rate
– 94% (for local stage), 18% (for distant stage)
• Case-fatality rate
– 23% of neonates with bloody D and fever die (e.g., Africa)
• In-hospital case-fatality (mortality) rate
– 5% of hospitalized patients die at hospital X.
• Attack rate
– 25% of passengers on a cruise ship got V&D
Mathew J. Reeves, Dept. of
Epidemiology, Mich State Univ.
Incidence Density Rate (IDR)
Defn: the speed at which a defined at-risk group or population
develops a new clinical condition or outcome over a given time
period.

• IDR = Number of newly disease individuals

Sum of time periods for all disease-free indv.-at-risk

• denominator is "person-time" or "population time“

• a measure of the instantaneous force or speed of disease

• IDR ranges from 0 to infinity (it is not a proportion!)

• dimension = per unit time or the reciprocal of time (time-1)

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
The Concept of “person-time”
• the sum of the disease-free time experience for individuals at risk in the
population

• Concept: 100 people followed for 6 months have same person-time

experience as 50 people followed for a year.
– 100 x 0.5 = 50 person-years
– 50 x 1.0 = 50 person-years

• How to calculate? (add up disease-free time)

– 100 subjects followed for 6 months
– 1 new case develops on day 1 of each successive month (i.e., 2 thru 6):
– Person time is the sum of disease free-time for each month (1 thru 6)
• = 100 + 99 + 98 + 97 + 96 + 95 = 585 months
– IDR = 5/585 person-months or 8.54 per 1,000 person months

• Person time can be measured with whatever scale that makes the most
sense i.e., person-days, person-weeks, person-months, person-years (PY)

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Incidence Density Rate (IDR)
• A measure of the “speed” that disease is occurring
• IDR answers the question: “At what rate are new cases of
disease occurring in the population”

• Common IDR’s
• Mortality rate (Vital Statistics)
– Lung CA mortality rate = 50 per 100,000 PY
– Breast CA mortality rate = 15 per 100,000 PY

• Disease Incidence Rates

– IDR of neonatal diarrhea = 280 per 1,000 child weeks

• Disease specific IDR rates

– Calculated for specific sub-sets defined by age, gender or race
• Black Men: Lung CA incidence rate = 122 per 100,000 PY
• Wh. Female: Lung CA incidence rate = 43 per 100,000 PY
Mathew J. Reeves, Dept. of
Epidemiology, Mich State Univ.
 Concept of the Prevalence “Pool”

New cases
(Incidence)

Recovery
Death
rate
rate

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Relationship between Prevalence and Incidence

• Prevalence is a function of:

• the incidence of the condition, and
• the average duration of the condition
– duration is influenced in turn by the recovery rate and mortality
rate

• Prev ~ Incidence x Duration

• This relationship explains why….

• Arthritis is common (“prevalent”) in the elderly
• Rabies is rare.
• Influenza is only common during epidemics.

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Measures of Effect
- Presentation and Interpretation of Information on Risk
• Information on the effect of a treatment can be
presented in several different ways

• Relative Risk (RR)

• Relative Risk Reduction (RRR)
• Absolute Risk Reduction (ARR)
• NNT (Number needed to treat)

• The way risk information is presented can have a

profound effect on clinical decisions (both on part of
patients and doctors)

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
 The 2 x 2 Table – Clinical Intervention Study (RCT)

Outcome

Yes No

Intervention (t) a b Riskt = a / a + b

Treatment
Group
Control c d Riskc = c / c + d
(placebo) (c)

(Risk = CIR)
Mathew J. Reeves, Dept. of
Epidemiology, Mich State Univ.
Example – RCT of Endoscopic Ligation vs. Endoscopic Sclerotherapy
For Bleeding Esophageal Varices (Stiegmann, NEJM, 1992)

Outcome

Death Survival

Ligation (t) 18 46 Riskt = 18 / 64

= 0.28
Treatment
Group
Sclerotherapy 29 36 Riskc = 29 / 65
= 0.45
(c)

Riskt and Riskc are the risks of death in the treatment and control
groups, respectively. Riskc is often referred to as the baseline risk.
Mathew J. Reeves, Dept. of
Epidemiology, Mich State Univ.
Relative Risk (RR) – RCT’s
• Defn: The relative probability (or risk) of the event in the
treatment group compared to the control group

• RR = Riskt /Riskc
• RR = 0.28 / 0.45 = 0.62

• Clinical interpretation (RCT):

• “the death rate after ligation treatment is 0.62 times lower than the
death rate after sclerotherapy treatment”

• A measure of the efficacy of a treatment

• Null value = 1.0.
• RR < 1.0 = decreased risk (beneficial treatment)
• RR > 1.0 = increased risk (harmful treatment)
• Not a very useful measure of the clinical impact of treatment
(need ARR)
Mathew J. Reeves, Dept. of
Epidemiology, Mich State Univ.
Relative Risk Reduction (RRR)
• Defn: The proportion of the baseline risk that is removed by
therapy

• RRR = 1 – RR
• RRR = 1 - 0.62 = 0.38 or 38%

• Clinical interpretation (RCT):

• “the death rate is 38% lower after ligation treatment compared to
sclerotherapy treatment”

• Indicates by how much in relative terms the event rate is

decreased.
• Also calculated as the ARR divided by the baseline risk
• ARR/ Riskc = [0.45-0.28]/0.45 = 38%
• Null value = 0.
Mathew J. Reeves, Dept. of
Epidemiology, Mich State Univ.
Absolute Risk Reduction (ARR)
• Defn: The difference in absolute risk (or probability of events) between
the control and treatment groups

• ARR = Riskc - Riskt

• ARR = 0.45 - 0.28 / = 0.17

• Clinical interpretation (RCT):

• “the absolute risk of death is 17% lower with ligation treatment compared to
sclerotherapy treatment”

• A simple and direct measure of the impact of treatment

• Also be called the risk difference (RD) or attributable risk

• The ARR depends on the background baseline risk which can vary
markedly from one population to another.

• Null value = 0.
Mathew J. Reeves, Dept. of
Epidemiology, Mich State Univ.
 Constant RRR (0.33) but varying ARR due to
different baseline risks

35
30
30

25
20
20 Control
%

15 Treatment
10
10 6.7
5
1 0.67
0
Population 1 Population 2 Population 3

ARR= 10% ARR= 3.3% ARR = 0.33%

Mathew J. Reeves, Dept. of
Epidemiology, Mich State Univ.
The Number Needed To Treat (NNT)
• Defn: The number of patients who would need to be treated to
prevent an adverse event

• NNT = 1 / ARR
NNT = 1 / 0.17 = 5.9 (or 6)

• Clinical interpretation (RCT):

• “for every 6 patients who received ligation treatment rather than
sclerotherapy treatment, one death is prevented”

• A very useful clinical measure because it is more interpretable

that the ARR and it conveys the impact of a clinical intervention
• NNT for primary stroke prevention for statins = 13,000 a year
• NNT for secondary stroke prevention for statins = 57 a year

• NNT depends on the efficacy of the intervention (= RRR) and

the underlying baseline risk

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Effect of Base-line Risk and Relative Risk
Reduction on NNT

Base-line Risk Relative Risk Reduction (RRR)

(%)
0.5 0.25 0.20 0.10
60 3 7 8 11
30 7 13 17 33
10 20 40 50 100
5 40 80 100 200
1 200 400 500 1000
0.1 2000 4000 5000 10000
Mathew J. Reeves, Dept. of
Epidemiology, Mich State Univ.
How information is conveyed (RRR,
ARR or NNT) makes a difference!
• Drug effects are perceived to be much more
favourable when they are presented as RRRs
rather than ARRs

• See article by Skolbekken in the course pack.

• Pay attention to how data on the effects of

drugs are framed in advertisements.

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Relative Risk (RR) – Cohort studies
• In cohort studies, RR is also used to measure the magnitude of
association between an exposure (risk factor) and an outcome (See
lecture 8).

• Defn: The relative probability (or risk) of disease in the exposed group
compared to the non-exposed group

• Example: Smoking and Lung CA

• IDR of lung CA death in heavy smokers = 4.17 per 1,000 person years
• IDR of lung CA death in non-smokers = 0.17 per 1,000 person years
• RR = Riskwxp /Riskunexp = 4.17/0.17 = 24.5

• Clinical interpretation (cohort):

• “the risk of dying of lung CA is about 25 times higher in lifetime heavy
smokers compared to lifetime non-smokers”

• Not a very useful measure of the impact of the risk factor in the
population (need PARF)

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.
Other important effect measures not
covered in this lecture
• Odds ratio (OR)
• See course notes, plus will be covered in the
lecture 9 on case-control studies

• Population attributable risk (PAR)

• (See course notes)

• Population attributable risk fraction (PARF)

• (See course notes)

Mathew J. Reeves, Dept. of

Epidemiology, Mich State Univ.