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.