Managerial Epidemiology
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.