cohort design
TRANSCRIPT
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Study Designs
observational studies
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Objectives
Define and understand design issues
relating to cohort studies
Understand concepts including: selection of
the cohort, defining the population at risk,
measurement of exposure, outcome status
and types of cohort data
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Incidence of Diabetes Among Dependents of the U.S. Military Forces
Admitted to U.S. Army Treatment Facilities, 1971-1991
Objective
To determine the national incidence of diabetes in children by
studying a group representing all parts of the country: thedependent children of U.S. Military personnel.
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Incidence of Diabetes Among Dependents of the U.S. Military Forces
Admitted to U.S. Army Treatment Facilities, 1971-1991
Research Design and Methods
Dates of admission, diagnosis of diabetes, age, and gender were
collected for all 522,326 children age 21 or younger, of active duty
military personnel admitted to US Army treatment facilitated
during fiscal years 1971-1991. Incidence rates were expressed as
cases per 100,000 person-years.
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Incidence of Diabetes Among Dependents of the U.S. Military Forces
Admitted to U.S. Army Treatment Facilities, 1971-1991
Results -
A total of 2308 cases of diabetes were diagnosed in 14.3 million
person-years of follow-up over the 21 years. The overall incidence
rate of diabetes in this population is 16.2 (95% CI 15.516.91)
For 1987-1991, the age-specific rates were 8.1 (0-4 years), 15.9 (5-
9 years, 25.6 (10-14 years), 23.9 (15-19 yrs), and 23.4 (20-21
years)
Conclusion ?????
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Epidemiologic definition of cohort
Chort: A group of individuals that share a
common characteristic
Example:
Birth cohort: individuals born in the same
period (often year)
Exposure cohort: individuals sharing a commonexposure (often an occupational exposure such
as asbestos, etc.)
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Definition of a cohort study
The observation of a cohort(s) over time to
measure a stated outcome.
Two primary purposes
Descriptive (measures of frequency)
To describe the incidence of an outcome over time
or to describe the natural history of diseaseAnalytic (measures of association)
To analyze the relation between occurrence of
outcomes and risk factors (or predictive factors)
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Cohort Studies: distinguishing features
Directionality: forward, incident cases
E D / D
PAR PAR = population at risk
E D / D
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Cohort Studies
(prospective, longitudinal)Usually undertaken when:
sufficient evidence has accumulated from other studies
to indicate a prospective cohort study is warranted
a new agent is introduced and requires monitoring forits possible association with adverse health outcomes
(levaquin, vioxx)
temporal association is unclear from a case-control
study
impressive results are obtained from a c-c study (either
positive or negative) and issues of validity (selection or
information bias) are evident or are a concern
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Is Mold Exposure a Risk Factor for Asthma?
A remarkably consistent association between homedampness and respiratory symptoms and asthma has beenobserved in
a large number of studies conducted across manygeographic regions .
In a recent review of 61 studies, it was concluded thatdampness was a significant risk factor for airway effectssuch as cough, wheeze, and asthma, with odds ratiosranging from 1.4 to 2.2.
Positive associations have been shown in infants,children, and adults, and
some evidence fordose-response relations has also beendemonstrated .
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Is Mold Exposure a Risk Factor for Asthma?
Although it has been concluded that the evidence
for a causal association between dampness and
respiratory morbidity is strong, this evidence isbased mainly on cross-sectional studies and
prevalence case-control studies;
few prospective studies have been conducted
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Cohort Study
Major Concerns
Selecting a cohort (sampling frame, sampling
and recruitment, external vs internal validity) Please read Delnevo et al paperposted on BB
Exposure assessment
Follow-up
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Selecting a Cohort
Population Based Cohort Studies
Population Subgroup Cohort Studies
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Selecting the Cohort
Population Based Cohort Studies
Any well-defined population (geographic,occupational, membership in HMOs)
Typically evaluate multiple hypotheses
Primary Justification :external validity
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Example: Nurses Health Study Begun in 1976
~ 270 published papers
Original study question = oral contraceptives and breastcancer
Many other areas researched
Cohort Married registered nurses
Between ages 30-55 (in 1976)
Living in 11 most populous states whose nursing
boards agreed to supply members names
122,000 out of 170,000 responded
Follow-up to date: 90%
Thoughts?
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Example: Nurses Health Study II Begun in 1989
Original study question: oral contraceptives, diet andlifestyle risk factors in a younger cohort
Planned to collect better exposure information (type ofOC, duration, important covariates)
Cohort Registered nurses, 25-42 years,
Sample size = 125,000
Recruitment: send a single questionnaire. Enroll all
eligible who respond 116,686 out of 517,000 enrolled
Follow-up to date: 90%
Thoughts?
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Example: Nurses Health Study III Currently enrolling
Female RNs and LPNs age 22-42 from around thecountry.
Research question: how new hormone preparations,dietary patterns and nursing occupational exposures
impact womans health. An invitational mailing sent to ~ 1 million nurses.
Thoughts?
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Selecting the Cohort, contd
Population Based Cohort Studies
Advantages
Estimation of distribution and prevalence of relevant
exposure variables Calculation of risk factor trends over time
Strong internal validity
Strong external validity (primary justification)
Disadvantages Expensive, logistically complicated
Often associated with large loss to follow-up
If exposure is rare, inefficient
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Selecting the Cohort, contd
Sampling Frame
Total population
Probability samples of the population
The extent to which a cohort sample is representative of the totalreference population depends on the completeness of the populationframe available to sample from as well as participation rates. please refer to Delnevo et al article as an example.
Similar to the concept of the source population
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Selecting the Cohort, contd
Population Based Cohort Studies :
External Validity Issues and Considerations
Depends on eligibility criteria for inclusion
Initial response of the sample
Stability of the cohort on follow-up.
Requires variability of exposure and outcomelevels
Susceptibility of the population to the risk factor
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Selecting the Cohort, contd
Example of the importance :
Have smokings risk been underestimated by US cohort
studies that exclude the poor. Presented at APHA,November 2000.
Source of smoking risk data based on nurses, Cancer
Society or MRFIT volunteers, HMO members.
- What do you think of the cohort??
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Selecting the Cohort: The non-exposed
internal comparison groups: select from the same
source population as Exposed
increases the likelihood that the E and E members are
from a similar subgroup of the population
generally have the same follow-up procedures andtherefore, the same likelihood that D will be detected
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Selecting the Cohort: The non-exposed
external comparison groups: chosen from a
different source population
often general population controls fromarea are used
- must be susceptible to the same selective
factors as the E group- less costly if data already available
- sometimes called SMR studies
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Selecting the Cohort, contd
Levels of subject selection:Target Population: population to which resultscan be applied
Source Population: the population, defined ingeneral terms and enumeratedif possible, from which eligiblesubjects are drawn
Eligible Population: the population of subjectseligible to participate
Study Participants: those people you contribute
data to the study
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Exposure: important issues
Definition of exposure: intensity, duration
Induction period
Latency
Changing exposures
Allocation of person-time in the above
examples
Categorizing exposure
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Exposure: important issues
Induction period
Duration of time that it takes from exposre to onset of
disease
Time during which exposure occurs time at risk
Example: radiation exposure and leukemia, ~3.5 years.
Exposure is classified as high, medium and low based on the
amount of time working in a job where you are exposed to
radiation PT at risk. What do you do with the person-time that accrues prior to the
induction time?
Only include time at risk of the outcome in the denominator of
the rate.
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Exposure: important issues
Latency period
Duration of time from disease initiation to
disease detection.Very relevant when considering covariates such
as detection bias, etc
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Exposure: important issues
Changing exposures:
Calculation of rates (as opposed to risks) allows flexibility in the
analysis of cohort data.
An individual can contribute follow-up to several different
exposure-specific rates, depending on details of the study
hypothesis
The definition of the exposure group corresponds to the definition
of PT eligible for each level of exposure.
How to handle changing exposures depends also on crossover effects. If the effect of being exposed is cumulative,
you can not change exposure groups when exposure
ceases.
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Exposure: important issues
Categorizing exposures
Often there is no guidance on appropriate categories of exposure.
Or the line between exposed and unexposed is not defined
No problem if your data are continuous
If you want to calculate rates directly, you must observe
populations within categories of exposure.
Common error: apportioning to PT time, the unexposed time of a
person who eventually becomes exposed.
Occupational study where exposure is categorized according to duration ofemployment in a particular job. Highest exposure category is at least 20 years
of employment. If a worker has been employed 30 years, it is a mistake to
assign that employee to the 20+ years of employment because they only
reached that exposure in the last 10 years. Thats the time frame relevant to
20+ years of exposure.
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Exposure: another issue, measurement
Is Mold Exposure a Risk Factor for Asthma?:
It is not clear whether molds are merely markers of
dampness or are causally related to the symptoms
associated with dampness.
Assessment of exposure to molds is often done by
questionnaire.
It is unknown to what extent questionnaire reports of
mold growth correlate with exposure to relevant mold
components .
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The Duration and Timing of Exposure: Effects of
Socioeconomic Environment on Adult Health (AM J Public
Health, 1999;89:1059-1065)
Objectives: This study investigated timing and
duration effects of SES on self-rated health at 33 yrs ofage and established whether health risks are modified
by changing SES and whether cumulative SES operated
through education.
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The Duration and Timing of Exposure: Effects of
Socioeconomic Environment on Adult Health (AM J Public
Health, 1999;89:1059-1065)
Methods: Data were from the 1958 British birth
cohort. Occupational class at birth and at 16, 23, and
33 years of age was used to generate a lifetime SES
score.
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The Duration and Timing of Exposure: Effects of
Socioeconomic Environment on Adult Health (AM J
Public Health, 1999;89:1059-1065)
Results: At 33 yrs of age, 12% of men and women reported poor
health.
SES at birth and at 16, 23 and 33 years of age wassignificantly associated with poor health for all ages.
No large differences in effect sizes emerged, suggestingthat timing was not a major factor.
Odds of poor health increased by 15% (men) and 18%
(women) with a 1-unit increase in the lifetime SESscore.
Strong effects oflifetime SES persisted afteradjustment for education level.
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Loss to Follow-up
Major portion of staff efforts are toward
reducing loss to follow-up.
Ways to reduce loss to follow-up ??
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Types of Cohort Studies
Concurrent
Retrospective
Mixed Design
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Disadvantages:
Costly, resource intensive (manpower, time and money)
Loss to follow-up of study subjects
Inefficient for studying diseases with long latency
Inefficient for studying rare diseases- example : If ID = 5 per 100,000 per year and sample size calculations
say you need 100 cases, given an initial cohort of 40,000
subjects follow-up would have to continue for 50 years
Study effects
Changing exposure
Withdrawals/loss to follow-up
Basic design allows only 1 risk factor to be studied
COHORT STUDIES