cohort design

7/28/2019 Cohort Design

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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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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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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


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


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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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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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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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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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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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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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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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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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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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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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

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