COHORT STUDIES

Overview

• Definition: A study in which two or more groups of people that are free of disease and that differ according to the extent of exposure (e.g. exposed and unexposed) are compared with respect to disease incidence

• Cohort studies are the observational equivalent of experimental studies but the researcher cannot allocate exposure -he must locate a natural experiment to observe the relationship between the exposure and disease

Overview

Example: Ranch Hand Study

• Exposed group: 1,264 Air Force servicemen who sprayed agent orange during Vietnam War, 1962-1971

• Unexposed group: 1,264 Air Force servicemen who flew other missions during Vietnam War

• Outcomes of interest: cancer, post traumatic stress, adverse pregnancy outcomes etc.

• Principle: If Agent Orange is not associated with the outcomes under study, then the outcome rates will be the same in both groups

Timing of cohort studies

• Retrospective: both exposure and disease have occurred at start of study

Exposure------------------------Disease *Study starts

• Prospective: exposure has (probably) occurred, disease has not occurred

Exposure----------------------Disease *Study starts

• Ambi-directional: elements of both

OverviewPrinciples of experimental studies applied to observational cohort Studies

1. Randomization of treatment so groups are comparable on known and unknown confounders. Can't randomize in an observational study so select a comparison group as alike as possible to the exposed group

 2. Use placebo in order to reduce bias. Can’t use placebo in

observational studies so you must make the groups as comparable as possible.

 3. Blinding to avoid bias in outcome ascertainment. In a cohort study,

it is crucial to have high follow-up rates and comparable ascertainment of outcomes in the exposed and comparison groups. You can blind the investigators conducting follow up and confirming the outcomes.

Timing of cohort studies

How do you choose between a retrospective vs. prospective design?

Retrospective:• Cheaper, faster

• Efficient with diseases with long latent period

• Exposure data may be inadequate

Prospective:• More expensive, time consuming

• Not efficient for diseases with long latent periods

• Better exposure and confounder data

• Less vulnerable to bias

Issues in design of cohort studies

Selection of exposed population

Choice depends upon hypothesis under study and feasibility considerations

Issues in design of cohort studies

Examples of exposed populations:

• Occupational groups

• Groups undergoing particular medical treatment

• Groups with unusual dietary or life style factors

• Professional groups (nurses, doctors)

• Students or alumni of colleges

• Geographically defined areas (e.g. Framingham)

Issues in design of cohort studies

For rare exposures, you need to assemble special cohorts (occupational groups, groups with unusual diets etc.)

Example of special cohort study• Rubber workers in Akron, Ohio• Exposure: industrial solvent• Outcomes: cancer

Issues in design of cohort studiesIf exposure is common, you may want to use a general cohort

that will facilitate accurate and complete ascertainment of data (Doctors, nurses, well-defined communities)

Example of general cohort study

• Framingham Study• Exposures: smoking, hypertension, family

history• Outcomes: heart disease, stroke, gout, etc.

Issues in design of cohort studiesSelection of comparison (unexposed) group

Principle: You want the comparison (unexposed) group to be as similar as possible to the exposed group with respect to all other factors except the exposure. If the exposure has no effect on disease occurrence, then the rate of disease in the exposed and comparison groups will be the same.

Counterfactual ideal: The ideal comparison group consists of exactly the same individuals in the exposed group had they not been exposed. Since it is impossible for the same person to be exposed and unexposed simultaneously, epidemiologists much select different sets of people who are as similar as possible.

Issues in design of cohort studies

Three possible sources of comparison group

• 1. Internal comparison: unexposed members of same cohort• Ex: Framingham study, Ranch Hand study

• 2. Comparison cohort: a cohort who is not exposed from another similar population• Ex: Asbestos textile vs. cotton textile workers

Issues in design of cohort studies• 3. General population data: Use pre-existing

data from the general population as the basis for comparison. General population is commonly used in occupational studies. Usually find healthy worker effect

• Ex. A study of asbestos and lung cancer with U.S. male population as the comparison group

Which of the three comparison groups is best?

Issues in design of cohort studiesSources of exposure information

Pre-existing records - inexpensive, data recorded before disease occurrence but level of detail may be inadequate. Also, records may be missing, usually don't contain information on confounders

Issues in design of cohort studiesSources of exposure information

• Questionnaires, interviews: good for information not routinely recorded but

have potential for recall bias

• Direct physical exams, tests, environmental monitoring may be needed to ascertain certain exposures.

Issues in design of cohort studies

Sources of outcome information

• Death certificates• Physician, hospital, health plan records• Questionnaires (verify by records)• Medical exams

Goal is to obtain complete follow-up information on all subjects regardless of exposure status. You can use blinding (like an experimental study) to ensure that there is comparable ascertainment of the outcome in both groups.

Issues in design of cohort studiesApproaches to follow-up

• In any cohort study, the ascertainment of outcome data involves tracing or following all subjects from exposure into the future.

• Resources utilized to conduct follow-up: town lists, Polk directories, telephone books; birth, death, marriage records; driver's license lists, physician and hospital records; relatives, friends.

• This is a time consuming process but high losses to follow-up raise doubts about validity of study

Ex. Tuberculosis treatment and breast cancer study

Analysis of cohort studies

• Basic analysis involves calculation of incidence of disease among exposed and unexposed groups.

• Depending on available data, you can calculate cumulative incidence or incidence rates.

• Recall set up of 2 x 2 tables.

Analysis of cohort studies

Example: Tuberculosis treatment and breast cancer study

• Followed 1,047 women who were treated with air collapse therapy and exposed to numerous fluoroscopic examinations (radiation) and 717 who received other treatments. A total of 47,036 woman-years of follow-up were accumulated during which 56 breast cancer cases occurred.

Analysis of cohort studies Breast

Cancer Cases

Woman-Years of follow-up

Exposed 41 28,001

Unexposed 15 19,025

Total 56 47,036

IR1 = 41/28,011 = 1.5/1,000 woman-years IR0 = 15/19,025 = 0.8/1,000 woman-years RR = IR1/IR0 = 1.9

Interpretation: Women exposed to fluoroscopies had 1.9 times the risk of breast cancer compared to unexposed women.

Strengths of Cohort Studies

• Efficient for rare exposures, diseases with long induction and latent period

• Can evaluate multiple effects of an exposure

• If prospective, good information on exposures, less vulnerable to bias, and clear temporal relationship between exposure and disease

Weaknesses of Cohort Studies• Inefficient for rare outcomes • If retrospective, poor information on

exposure and other key variables, more vulnerable to bias

• If prospective, expensive and time consuming, inefficient for diseases with long induction and latent period

• Keep these strengths and weaknesses in mind for comparison with case-control studies