cohort studies principles of epidemiology lecture 9 dona schneider, phd, mph, face
TRANSCRIPT
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)
PHCO 0502 Principles of Epidemiology (Schneider)
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)
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
Disease-FreeCohort
Single Sample Cohort Study Design
Target Population
Exposed
Not Exposed
Diseased
Not Diseased
Diseased
Not Diseased
TIME
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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.
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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.
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
Multi-Sample Cohort Study Design
Study Cohort
Exposed
Not Exposed
Diseased
Not Diseased
Diseased
Not Diseased
TIME
Control Cohort
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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?
PHCO 0502 Principles of Epidemiology (Schneider)
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?
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
Cohort study data collection (pg. 221)
DEEHistorical prospective
DERetrospective
DEProspective
FUTUREPRESENTPASTDESIGN
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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