Observational Studies: Cohort Studies

PBHE 6200: Epidemiology 1

October 29, 2019

 Objectives
By the end of this lecture you should be able to:

• Compare and contrast a cohort study with an experimental study

• List the two types of cohort studies

• Discuss the similarities and differences between the types of cohort

studies

• Describe common biases in cohort studies

• Discuss the strengths and limitations of all cohort studies

 What is a cohort?
A group of persons with a common demographic or statistical
characteristic (Canadian Oxford Dictionary, 2004)

A group of persons who were born in the same year or same

period (Merrill, Intro to Epidemiology, 2006)

Any group of persons who are followed or traced over a period

of time (Last, Dictionary of Epidemiology, 2001)

A group of individuals followed or traced through time (Gordis,

Epidemiology, 2008)
 What is a cohort study?

The analytic method of epidemiologic study in which subsets of a

defined population can be identified who are, have been, or will
be exposed or not exposed, in different degrees, to a factor or
factors hypothesized to influence the probability of occurrence of
a given disease or other outcome.

Last, Dictionary of Epidemiology, 2001

 What is a cohort study?

Follows a group of people with a common characteristic over a

specified period of time to determine the probability of disease
occurrence

Common characteristic

Probability of Disease Occurrence

 Schematically …..

Defined Study
Population

Exposed Unexposed

Disease (Event) No Disease ( No Event) Disease (Event) No Disease (No Event)

 Cohort Studies vs. Experimental Studies
Similarities

Differences
Why not always use an experimental study?

Ethics of randomization to a putatively harmful risk factor

Practicality of randomization

More costly than a cohort study

 Features of a cohort study
Follows a group of people with a common characteristic over a
specified period of time to determine the probability of disease
occurrence

1. Formulate a hypothesis

2. Selection of Study Subjects

Same Stage
3. Determine exposure status

(Follow for a specified time interval)

4. Determine the probability of disease occurrence in

exposed and unexposed cohorts
 Selection of Subjects

Based on exposure

From the study population of interest

 Based on exposure

Exposed Unexposed

Disease (Event) No Disease ( No Event) Disease (Event) No Disease (No Event)

From the general population

Defined Study
Population

Exposed Unexposed

Disease (Event) No Disease ( No Event) Disease (Event) No Disease (No Event)

 When might you use each approach?
Based on exposure

From the general population

 Determining probability of disease occurrence
What does that involve?
• compare incidence in exposed and unexposed

How do we calculate incidence?

• Incidence Proportion

• Incidence Rate
Incidence Proportion

Number of Events
Number at Risk
Incidence Rate

Number of Events
Total Person Time contributed among those at Risk
Consider a cohort study that wants to investigate the association
between HRT (hormone replacement therapy) use and
endometrial (uterine) cancer

Since the purpose is to estimate incidence, should we include:

Men (?)

Women with hysterectomies (i.e. removal of uterus) (?)

Women with endometrial cancer (?)

A total of 4023 post-menopausal women were followed for 7
years. The researchers were interested in whether exposure
to hormone therapy increased risk for breast cancer death.
How do you compare the relative
difference of two incidence proportions?

HRT HRT Total

users non-
users
Breast cancer 102 260 362
Total Persons 884 3139 4023
Incidence 0.115 0.083 4385
Proportion
 Attributable risk
Excess risk = attributable risk (AR) = the absolute
difference in the incidence rate between the
exposed population and the unexposed population
Example: If 10% of the unexposed and 15% of the
exposed became ill during the study period, then
the excess risk in the exposed was 15% – 10% = 5%

This number represents the additional risk of

disease in the exposed that can be attributed to
the exposure
Attributable
risk vs.
attributable
risk percent
How do you compare the absolute difference of two incidence
proportions?
HRT users HRT non- Total
users

Breast cancer 102 260 362

Total Persons 884 3139 4023

Incidence Proportion 0.115 0.083 4385

How do you compare the relative difference of two incidence
rates?

HRT HRT non- Total

users users

Breast cancer 260 102 362

Total Person-Years 8300 7114 15414

Incidence Rates 0.031 0.014

How do you compare the absolute difference of two incidence
rates?

HRT users HRT non- Total

users

Breast cancer 260 102 362

Total Person-Years 8300 7114 15414

Incidence Rates 0.031 0.014

Relative risk
Exposed Incidence

Unexposed Incidence
 Types of Cohort Studies

1. Prospective (Concurrent)

2. Retrospective (Historical)
 Prospective Cohort

• Identify exposed and unexposed individuals in the

present and follow them over time to determine the
incidence of disease
• Example: Identify a sample of new mothers in the
maternity ward. Determine which mothers
breastfeed and which do not. Follow these women
for 2 years to determine the incidence of sudden
infant death syndrome.
 Issues with Prospective Studies
Strengths

Limitations
 Retrospective Cohort
• Identify exposed and unexposed individuals from
historical records and follow them to the present to
determine the incidence of disease
example: locate hospital records from maternity wards
from 2006. Identify infants who were breast-fed and
infants who were not. Follow these infants to the
present (i.e. 2 years later) to determine the incidence
of sudden infant death syndrome
 Issues with Retrospective Studies
Strengths

Limitations
An epidemiologist is interested in exploring the
association between infant breastfeeding and
sudden infant death syndrome

Should she use a prospective or a retrospective

cohort study???
Retrospective
Locate hospital records from maternity wards from
2006. Identify infants who were breast-fed and
infants who were not. Follow these infants to the
present (i.e. 2 years later) to determine the
incidence of sudden infant death syndrome

Prospective
Identify a sample of new mothers in the maternity
ward today. Determine which mothers breastfeed
and which do not. Follow these women for 2 years
to determine the incidence of sudden infant death
syndrome.
Retrospective Study

Exposed Unexposed

Disease (Event) No Disease ( No Event) Disease (Event) No Disease (No Event)

 Key Features of Cohort Studies

Inclusion in study defined by - exposure

Exposure precedes the outcome - temporality

Calculation of incidence rate

 Bias in Observational Studies
Selection
When those who select to participate in the study
are different from those who select not to participate
in the study

Information
When the information gathered in study cohorts
leads to a misclassification of exposure and/or
outcome
 Common bias in cohort studies

Selection
‘Healthy Worker Effect’

Attrition

Information

Interviewer bias
Strengths of cohort studies

Clear Temporal Sequence

Can Calculate Incidence Rates

Collect (generally) unbiased measures of exposure

Study multiple diseases (outcomes)

Study rare exposures

Provide information on natural history of disease

Limitations of cohort studies
Size

Cost

Attrition

Changes to Exposure Level (retrospective)

Biased ascertainment of disease

Duration of Study
 Some important cohort studies

Framingham Heart Study

Nurses Health Study

European Prospective investigation of cancer (EPIC)

National Population Health Survey

 Smoking Boosts Aneurysm Risk for Women
http://www.healthzone.ca/health/article/517362

Coffee, Breast Cancer Link Disproven

http://www.healthzone.ca/health/article/516776

Obesity Linked to Prostate Cancer Deaths

http://www.theglobeandmail.com/servlet/story/RTGAM.20081005.wprostate0510/Ema
ilBNStory/specialScienceandHealth/home
 Coffee, Breast Cancer Link Disproven
http://www.healthzone.ca/health/article/516776

CHICAGO–A study of nearly 40,000 women has found no

overall link between caffeine and breast cancer, though
some women who have benign breast lumps might be at a
higher risk, researchers said yesterday.

… 38,432 American women who were studied over several

years starting in 1992 found "no overall association
between caffeine consumption and breast cancer risk," …
 Obesity Linked to Prostate Cancer Deaths
http://www.theglobeandmail.com/servlet/story/RTGAM.20081005.wprostate0510/Ema
ilBNStory/specialScienceandHealth/home

Men battling prostate cancer are more than twice as likely to die
from the disease if they are obese, according to a new study that
suggests soaring insulin levels related to excess weight are to blame.
… The study found that obese men with prostate cancer are 2.5
times more likely to die from the disease than patients of a healthy
weight….
Men who were overweight (a BMI of 25 to 29.9) or obese (a BMI of
greater than 30) before diagnosis were significantly more likely to
die from their prostate cancer than men of normal weight, the
researchers found.
 Smoking Boosts Aneurysm Risk for Women
http://www.healthzone.ca/health/article/517362

…researchers found that female smokers are four times more

likely to have an aortic aneurysm rupture or need repair,
compared to women who have quit smoking.
…. women who smoke have an eight-fold higher risk of rupture or
the need for repair than those who never took up the habit,

The research … looked at risk factors for rupture and repair of

abdominal aortic aneurysms in almost 162,000 postmenopausal
women, who were followed for an average of about eight years.
 Summary
Cohort study

• Similar in principle to RCT – no randomization

- No fixed exposure

• Follow exposed across time – prospective and retrospective

• Determine incidence of disease – ‘at risk’

• Calculate several measures of effect

• Clear temporal sequence