Cohort Studies Principles of Epidemiology Lecture 9 Dona Schneider, PhD, MPH, FACE.

Cohort Studies

Principles of Epidemiology

Lecture 9

Dona Schneider, PhD, MPH, FACE

PHCO 0502 Principles of Epidemiology (Schneider)

Cohort Studies Type of Analytic study

Unit of observation and analysis: Individual (not group)

Also called follow-up studies, incidence studies, panel studies, longitudinal studies, or prospective studies

Assembling a Cohort Cohorts may be chosen because they represent

The general population (i.e., the outcome of interest has a high incidence rate)

Special exposure groups (e.g., smokers, uranium miners or asbestos workers with high levels of specific exposures)

Special resource groups (e.g., alumni, physicians, nurses)

Geographically or facility-defined groups (e.g., Three Mile Island, hospitals with specialized maternity care)


Design At baseline (1st observation point):

Subjects are all disease free

Exposure is used to classify subjects into exposed or unexposed groups

Subjects are followed to document incidence (2nd observation point)


Assembling the Cohort

Before beginning the study, determine who is susceptible and who is immune to the outcome of interest You may need to do this with diagnostic tests

or medical histories


Disease-FreeCohort

Single Sample Cohort Study Design

Target Population

Exposed

Not Exposed

Diseased

Not Diseased

Diseased

Not Diseased

TIME


The Framingham Study

Since 1948, samples of residents of

Framingham, Massachusetts, have

been subjects of investigations of risk

factors in relation to the occurrence of

heart disease and other outcomes


The Framingham Study Hypotheses:

Persons with hypertension develop CHD at a greater rate than those who are normotensive.

Elevated blood cholesterol levels are associated with an increased risk of CHD.

Tobacco smoking and habitual use of alcohol are associated with an increased incidence of CHD.

Increased physical activity is associated with a decrease in development of CHD.

An increase in body weight predisposes a person to CHD.


The Framingham Study Study population consisted of 5,127 men and women

between ages 30 and 62 years and were at the time of

entry free of cardiovascular disease (1948-1952)

Cohort was examined every 2 years and by daily

surveillance of hospitalizations at Framingham

Hospital


The Framingham Study Exposures included:

Smoking

Alcohol use

Obesity

Elevated blood pressure

Elevated cholesterol levels

Low levels of physical activity, etc.

Comparison (Control) Groups With a one-sample (population-based) cohort, exposure is unknown

until after the first period of observation Example:

Select the cohort (all residents of Framingham) All members of the cohort are given questionnaires, and/or clinical

examinations, and/or testing to determine exposure status The cohort is then divided into exposure categories based on those results The nonexposed become the internal controls For continuous variables, such as caloric intake or amount of exercise,

multiple levels of exposure are constructed It is common to break exposure into quantiles (equally ordered subgroups)

and to use the extremes as the comparison (referent) group


Question

How does the design of a cohort study change if everybody in the cohort is exposed (special exposure cohort)?

Example: All persons exposed to radiation from the Chernobyl accident.


Answer You need to select a separate control cohort people

as similar as possible to the exposed cohort (income, age, gender, employment) but with no exposure

If you cannot find a comparison group, you may use available population incidence rates under certain circumstances


Multi-Sample Cohort Study Design

Study Cohort

Exposed

Not Exposed

Diseased

Not Diseased

Diseased

Not Diseased

TIME

Control Cohort


Selecting Comparison (Control) Groups If the cohort is the general population, subjects are selected

based on exposure and the comparison group is internal - from the same sample - who do not have the exposure

If the cohort is based on a high risk population selected on the basis of a given exposure (e.g., Chernobyl residents, asbestos workers), external controls must be sought

Sometimes both comparison groups are sought This eliminates the healthy worker effect and confounding for etiologic

agents other than the exposure of interest


Selecting Comparison Groups (cont.) If a comparison group cannot be assembled, known

population rates for outcomes may be acceptable but only if they are adjusted for the exposure Lung cancer rates are based on the population but should

not be used for comparison to compare to populations with high smoking rates, such as miners. WHY?

Leukemia rates from the general population can be used to compare rates to Three Mile Island residents. WHY?


Determining Exposure Valid means of determining exposure include:

Questionnaires Laboratory tests Physical measurements Special procedures Medical records

What if the exposure is chronic, such as radon or smoking?


Measuring Disease You must determine endpoints in a similar manner for

both the exposed and the non-exposed

That is, procedures for disease identification must be the same for the exposed and the non-exposed

Define the outcomes of interest (set diagnostic criteria)

If you are looking for multiple outcomes, each must be defined

Measuring Disease (cont.) Mortality may be ascertained from medical records, autopsy

records, death certificates, physician records, or next-of-kin Using mortality records does not allow for multiple outcomes

Hospital records can be scanned for specific types of admissions Health records of employers and schools can be monitored Reportable diseases may be ascertained from state registries

Absenteeism may be monitored with work records, self reporting, school records or household surveys

Common ailments that do not usually require medical care may be monitored through self-reports, telephone surveys or calendar sheets


Relative Risk (RR) A ratio that measures the risk of disease among the

exposed to the risk among the unexposed

RR Numerator: Incidence rate in the exposed

RR Denominator: Incidence rate in the unexposed


224

176

No CHD

(Controls)

31288Non-

smoker

288112SmokerExposure Status

TOTALCHD cases

(Cases)

Disease Status

Example: Calculating the Relative Risk

Relative Risk = =A/(A+B)

B/(C+D)

112 / 288

88 / 312= 1.38


Example: Interpreting the Relative Risk

Relative Risk = 1.38

The risk of developing CHD is 38% higher for a smoker than for a nonsmoker.

The risk of developing CHD is 1.38 times higher for a smoker than for a nonsmoker.

or


Exposure increases

disease risk(Risk factor)

Particular exposure is not

a risk factor

Exposure reduces disease risk

(Protectivefactor)

Exposure as a risk factor for the disease?

Risk for disease is higher in the exposed than in the unexposed

Risk of disease is equal for exposed and unexposed

Risk for disease is lower in the exposed

than in the unexposed

Risk comparison between exposed and unexposed

RR>1RR=1RR<1


Types of Cohort Studies Prospective

Exposure baseline in the present Follow-up period: present to future

Retrospective: Exposure baseline in the past Follow-up period: past to present

Historical prospective or ambispective: Exposure baseline in the past Follow-up period: past to present to future


Cohort study data collection (pg. 221)

DEEHistorical prospective

DERetrospective

DEProspective

FUTUREPRESENTPASTDESIGN


Types of Cohort Studies (cont.) You may also NEST a case-control study within a cohort study

Example: Begin with a cohort of 10,000 individuals without rheumatoid arthritis Test for the presence of RA antigen Assume those with RA antigen are the exposed and those without the

controls Follow for 10 years and determine the incidence of disease among both

cohorts This reduces the cost of testing


Outcome Measures Incidence in the exposed

Incidence in the unexposed

Relative risk

Attributable risk (risk difference)

Population attributable risk

Attributable risk percent

Population attributable risk percent

Standardized mortality ratio


Advantages of Cohort Studies Temporality: Exposure precedes outcome because the cohort is

disease free at baseline

Efficient for studying rare exposures

May be used to study multiple outcomes

Allows for calculation of incidence of diseases in exposed and unexposed individuals

Minimizes recall bias


Tend to be expensive (large sample size) and time consuming (long follow-up period)

Loss to follow-up

When multiple outcomes or specific disease incidence is the outcome of interest, bias can be a serious problem

Inefficient to study rare diseases

Disadvantages of Cohort Studies


Disadvantages of Cohort Studies (cont.) Nonparticipation (selection bias) – it cannot be

assumed that those who chose to participate had the same prevalence of exposures nor incidence of disease as those who did not participate

A difference in prevalence of exposure in nonparticipants will not bias the results

A difference in rate of disease among nonparticipants will bias the results

Cohort Studies Principles of Epidemiology Lecture 9 Dona Schneider, PhD, MPH, FACE.

Documents

framingham hospital

cohort cohorts

face slide

framingham study exposures

diseased time slide

incidence studies

framingham study hypotheses

dona schneider