Managerial Epidemiology: Assignment Week 3
Study Designs: Cohort
Studies
Chapter 7
Learning Objectives
• Differentiate cohort studies from other study designs
• List main characteristics, advantages, and disadvantages of cohort studies
• Describe three research questions that lend themselves to cohort studies
• Calculate and interpret a relative risk
• Give three examples of published studies discussed in this chapter
Temporality
• Temporality refers to the timing of
information about cause and effect.
• Did the information about cause and effect
refer to the same point in time?
• Or, was the information about the cause
garnered before or after the information
about the effect?
Limitations of Other Study
Designs
• Demonstrating temporality is a
difficulty of most observational
studies.
Limitations of Other Study
Designs (cont’d)
• Cross-sectional and case-control study designs are based on exposure and disease information that is collected at the same time.
• Advantage: Efficient for generating and testing hypotheses.
• Disadvantage: Leads to challenges regarding interpretation of results.
Limitations of Other Study
Designs (cont’d)
• Cross-sectional studies:
– Present difficulties in distinguishing the
exposures from the outcomes of the disease,
especially if the outcome marker is a
biological or physiological parameter.
Limitations of Other Study
Designs (cont’d)
• Case-control studies:
– Raise concerns that recall of past
exposures differs between cases and
controls.
Limitations of Other Study
Designs (cont’d)
• There has been no actual lapse of time
between measurement of exposure and
disease.
• None of the previous study designs is well
suited for uncommon exposures.
What is a cohort?
• A cohort is defined as a population group,
or subset thereof, that is followed over a
period of time.
• The term cohort is said to originate from
the Latin cohors, which referred to one of
ten divisions of an ancient Roman legion.
What is a cohort? (cont’d)
• Cohort group members experience a
common exposure associated with a
specific setting (e.g., an occupational
cohort or a school cohort) or they share a
non-specific exposure associated with a
general classification (e.g., a birth
cohort—being born in the same year or
era).
Cohort Effect
• The influence of membership in a particular cohort.
• Example: Tobacco use in the U.S.
– Fewer than 5% of population smoked around the early 1900s.
– Free cigarettes for WWI troops increased prevalence of smoking in the population.
– During WWI, age of onset varied greatly; then people began smoking earlier in life.
– One net effect was a shift in the distribution of the age of onset of lung cancer.
Cohort Analysis
• The tabulation and analysis of morbidity or
mortality rates in relationship to the ages
of a specific group of people (cohort)
identified at a particular period of time and
followed as they pass through different
ages during part or all of their life span.
Wade Hampton Frost
• Popularized cohort analysis method.
• Arranged tuberculosis mortality rates in a
table with age on one axis and year of
death on the other.
• One can quickly see the age-specific
mortality for each of the available years on
one axis and the time trend for each age
group on the other.
Wade Hampton Frost
Life Table Methods
• Give estimates for survival during time
intervals and present the cumulative
survival probability at the end of the
interval.
• Example: Life tables can be constructed to
portray the survival times of patients in
clinical trials.
Life Table Methods (cont’d)
• There are two life table methods:
– Cohort Life Table
– Period (Current) Life Table
Life Table Methods (cont’d)
• Cohort life table:
– Shows the mortality experience of all persons
born during a particular year, such as 1900.
• Period life table:
– Enables us to project the future life
expectancy of persons born during the year
as well as the remaining life expectancy of
persons who have attained a certain age.
Describing the Mortality
Experience of the Population
• Years of Potential Life Lost (YPLL)
• Disability-adjusted life years (DALYs)
YPLL
• Years of potential life lost (YPLL)
– Computed for each individual in a
population by subtracting that person’s life span from the average life
expectancy of the population
DALYs
• Disability-adjusted life years (DALYs)
– Adds the time a person has a disability
to the time lost to early death
Survival Curves
• A method for portraying survival times
• In order to construct a survival curve, the
following information is required:
– Time of entry into the study
– Time of death or other outcome
– Status of patient at time of outcome, e.g.,
dead or censored (patient is lost to follow-up)
Cohort Studies
• Start with a group of subjects who lack a
positive history of the outcome of interest
and are at risk for the outcome
• Include at least two observation points:
one to determine exposure status and
eligibility and a second (or more) to
determine the number of incident cases
Cohort Studies (cont’d)
• Permit the calculation of incidence rates
• Can be thought of as going from cause to effect
• The individual forms the unit of observation and
the unit of analysis.
• Involve the collection of primary data, although
secondary data sources are used sometimes
for both exposure and disease assessment
Cohort Studies
Timing of Data Collection
Sampling and Cohort Formation
Options
• Cohort studies differ according to
sampling strategy used.
• The two strategies are population-
based samples and exposure-based
samples.
Population-Based Cohort Studies
• The cohort includes either an entire population or a representative sample of the population.
• Population-based cohorts have been used in studies of coronary heart disease.
Framingham Study
• Conducted in Framingham, Massachusetts
• Ongoing study of CHD initiated in 1948
• Used a random sample of 6,500 from targeted age range of 30 to 59 years
Tecumseh Study
• Conducted in Tecumseh, Michigan
• A total community cohort study
• Examined the contribution of environmental and constitutional factors to the maintenance of health and origins of illness
• Started in 1959-1960 and enrolled 8,641 (88% of the community)
Population-Based Cohort
Studies (cont’d)
• Exposures unknown until the first period of
observation when exposure information is
collected
• Examples: After administration of
questionnaires, collection of biologic
samples, and clinical examinations, there
can be two or more levels of exposure.
Exposure-Based Cohort Studies
• These studies overcome limitations of
population-based cohort studies, which
are not efficient for rare exposures.
• Certain groups, such as occupational
groups, may have higher exposures than
the general population to specific hazards.
Definition of Exposure-Based
Cohort
• An exposure-based cohort is made up of
subjects with a common exposure.
• Examples:
– Workers exposed to lead during battery
production
– Childhood cancer survivors
– Veterans
– College Graduates
Comparison (Non-Exposed Group)
• Cohort studies involve the comparison of
disease rates between exposed and non-
exposed groups.
• The comparison group is similar in
demographics and geography to the
exposed group, but lacks the exposure.
• In an occupational setting, several
categories of exposure may exist.
Outcome Measures
• Discrete Events
–Single events and multiple occurrences
• Levels of Disease Markers
• Changes in Disease Markers
–Rate of change, change in level within
time
Temporal Differences in Cohort
Designs
• There are several variations in cohort
designs that depend on the timing of data
collection.
• These variations are:
– prospective cohort studies
– retrospective cohort studies
Prospective Cohort Study
• Purely prospective in nature;
characterized by determination of
exposure levels at baseline (the present),
and follow-up for occurrence of disease at
some time in the future
Advantages of Prospective
Cohort Studies
• Enable the investigator to collect data on
exposures; the most direct and specific
test of the study hypothesis
• The size of the cohort is under greater
control by the investigators
Advantages of Prospective Cohort
Studies (cont’d)
• Biological and physiological assays can be
performed with decreased concern that the
outcome will be affected by the underlying
disease process.
• Direct measures of the environment (e.g.,
indoor radon levels, electromagnetic field
radiation, cigarette smoke concentration) can
be made.
Retrospective Cohort Study
• Despite substantial benefits of prospective
cohort studies, investigators have to wait
for cases to accrue.
• Retrospective cohort studies make use of
historical data to determine exposure level
at some baseline in the past.
Advantages of Retrospective
Cohort Studies
• A significant amount of follow-up may be accrued in a relatively short period of time.
• The amount of exposure data collected can be quite extensive and available to the investigator at minimal cost.
Historical Prospective Cohort Study
• A design that makes use of both
retrospective features (to determine
baseline exposure) and prospective
features (to determine disease incidence
in the future)
• Also known as an ambispective cohort
study
Practical Considerations Regarding
Cohort Studies
• Availability of exposure data
• Size and cost of the cohort used
• Data collection and data management
• Follow-up issues
• Sufficiency of scientific justification
Availability of Exposure Data
• High quality historical exposure data are
absolutely essential for retrospective
cohort studies.
• Need to trade off between a retrospective
study design (with the benefits of more
immediate follow-up time) and collection of
primary exposure data in a prospective
cohort design.
Size and Cost of the Cohort
• The larger the size of the cohort, the
greater the opportunity to obtain findings
in a timely manner.
• Resource constraints typically influence
design decisions.
Data Collection and Data
Management
• Larger studies are more demanding than
smaller ones; challenges due to data
collection and data management.
• Explicit protocols for quality control (e.g.,
double entry of data and scannable
forms) should be considered in the
design and implementation stage.
Data Collection and Data
Management (cont’d)
• Organizational and administrative burdens are
increased when there are multiple levels of data
collection (such as phone interviews, mailed
questionnaires, consent forms to access
medical records).
Follow-up Issues
• There are two types of follow-up:
–Active follow-up
–Passive follow-up
Active Follow-up
• The investigator, through direct contact
with the cohort, must obtain data on
subsequent incidence of the outcome
(disease, change in risk factor, change in
biological marker).
• Accomplished through follow-up mailings,
phone calls, or written invitations to return
to study sites/centers.
Active Follow-up (cont’d)
• Example: Minnesota Breast Cancer
Family Study
– Mailed survey
– A reminder postcard 30 days later
– A second survey
– A telephone call to non-responders
Passive Follow-up
• Does not require direct contact with cohort
members.
• Possible when databases containing the
outcomes of interest are collected and
maintained by organizations outside the
investigative team.
• Example: Used in the Iowa Women’s Health Study.
Sufficiency of Scientific
Justification
• There should be considerable scientific rationale for a cohort study.
• Additional justification for cohort studies may come from laboratory experiments or animal studies.
• Cohort studies are the only observational study design that permits examination of multiple outcomes.
Cohort Studies:
Measures of Effect
• Relative risk is the ratio of the risk of disease or
death among the exposed to the risk among the
unexposed.
• Recall that risk is estimated in epidemiologic
studies only by the cumulative incidence.
• When the relative risk is calculated with
incidence rates or incidence density, then the
term rate ratio is more precise.
Relative Risk
Relative risk =
Incidence rate in the exposed
Incidence rate in the non-exposed
Relative Risk
• Using the notation from the 2 by 2
table, the relative risk can be
expressed as
[A/(A+B)] / [C/(C+D)]
Measures of Association
(cont’d)
Disease Status
Incidence
Exposure Yes No Totals Total
Status
Yes A B A+B A/(A+B)
No C D C+D C/(C+D)
A + C B + D N
Relative Risk [A/A+B]/[C/C+D]
Cohort Studies:
Sample Calculation
• Is there an association between child abuse
and suicide attempts among chemically
dependent adolescents?
• Source: Deykin EY, Buka SL. Am J Public
Health. 1994;84:634-639.
Sample Calculation (cont’d)
Examples of Major Cohort Studies
• The Alameda County Study
– Studied factors associated with health and mortality
– Involved residents of Alameda County, CA, ages 16-94 years
– Data collected through mailed questionnaires; telephone interviews or home interviews of non-respondents
– Follow-up with same procedures at years 9, 18, and 29
Examples of Major Cohort Studies
(cont’d)
• Honolulu Heart Program
– Studied coronary heart disease and stroke in
men of Japanese ancestry
– Involved men of Japanese ancestry living on
Oahu, HI, ages 45-65 years
– Data were collected through mailed
questionnaires, interviews, and clinic
examinations.
Examples of Major Cohort
Studies (cont’d)
• Nurses’ Health Study
– Originally studied oral contraceptive use;
expanded to women’s health
– Married female R.N.s ages 30-55 years
– Data collected through mailed questionnaires
– Follow-up every 2 years; toenail sample at
year 6 and blood sample at year 13
Nested Case-Control Studies
• A nested case-control study is defined as a type
of case-control study “. . . in which cases and
controls are drawn from the population in a
cohort study.”
• Example: nested case-control breast cancer
study
– Controls are a subset of the source population for
the cohort study of breast cancer.
– Cases of breast cancer identified from the cohort
study would comprise the cases.
Advantages of Nested Case-
Control Studies
• Provide a degree of control over
confounding factors.
• Reduce cost because exposure
information is collected from a subset of
the cohort only.
• An example is an investigation of suicide
among electric utility workers.
Strengths of Cohort Studies
• Permit direct determination of risk.
• Time sequencing of exposure and
outcome.
• Can study multiple outcomes.
• Can study rare exposures.
Limitations of Cohort Studies
• Take a long time
• Costly
• Subjects lost to follow-up
Table 7-6
• Table 7-6 summarizes various study
designs by comparing their characteristics,
advantages, and disadvantages.