Epidemiologic Study Designs

Nancy D. Barker, MS

Epidemiologic Study Design The plan of an empirical investigation to

assess an E – D relationship.

Exposure• Alcohol consumption

• Raw hamburger

• Smoking

Health Outcome• Breast Cancer

• E. Coli

• Lung Cancer

Type of Epidemiologic Studies

• Experimental: Randomization to exposure

• Observational: No randomization

Experimental Studies

The investigator through randomization allocates subjects to different categories of exposure.

Randomization: An allocation procedure that assigns subjects into (one of the) exposure groups being compared so that each subject has the same probability of being in one group as in any other.

Randomization

• Tends to make demographic, behavioral, genetic, and other characteristics of the comparison groups similar except for their exposure status.

• If the study finds any difference in health outcome between the comparison groups, that difference can only be attributable to their difference in exposure status.

Experimental Studies

Advantage:• Randomization – unmeasured variables evenly

distributed among exposure• Potential for bias is low

Disadvantage:• Ethical concerns• Cost• Length of study• Not good for rare D

Observational Studies

• Investigator observes the exposure and outcome status of each

• Most Epidemiologic studies are observational

Observational Studies

• Descriptive Studies

• Analytic Studies

Observational Studies

Descriptive StudiesTo organize and summarize data according

to time, place, and person. Why?

• Describe natural history of disease• Extent of public health problem• Identify populations at greatest risk• Allocation of health care resources• Suggest hypothesis about causation

Observational Studies

Analytic StudiesUsed to quantify the association between an

exposure (E) and a health outcome (D), and to test hypotheses about causal relationships.

• Provides a control group (baseline)• Test hypotheses about determinants• Causation

Causation

In any research field involving the conduct of scientific investigations and the analysis of data derived from such investigations to test etiologic hypotheses, the assessment of causality is a complicated issue.

In particular, the ability to make causal inferences in the health sciences typically depends on synthesizing results from several studies, both epidemiologic and non-epidemiologic (e.g., laboratory or clinical findings).

Observational Studies

Advantage:• Natural Setting• Addresses ethical concerns

Disadvantage:• No randomization – investigator can only account

for variables measured.

Common Observational Study Designs

• Cohort Study

• Case-Control Study

• Cross-sectional Study

Design Options

• Directionality

• Timing

Directionality

• When the exposure variable is observed relative in time to when the health outcome is observed.

Forward Directionality

Forward Directionality

Backwards Directionality

Backwards Directionality

Non-Directionality

Timing

• Timing concerns whether the health outcome of interest, and therefore all study events, has already occurred before the study actually began.

Retrospective

Prospective

Retrospective or Prospective

Cohort Study

• Directionality: Always forward

• Timing: Prospective or Retrospective

Cohort Study

Synonyms:

• Follow-up study

• Longitudinal study

• Incidence study

Cohort Study Example

Example:

Prospective:

Framingham Heart Study (ActivEpi)

Retrospective:

VDTs and spontaneous abortions (ActivEpi)

The Exposure Variable in Cohort Studies

• If E is common, sample from large population, then divide into E and not E.

• If E is rare, sample E from special population, then sample not E from external comparison group.

• Caution: Healthy worker effect.

Cohort Study

• Advantages– Forward directionality

– Free of certain selection biases

– Prospective cohort less prone to obtaining incorrect information

– Can study several diseases

– Useful for examining rare exposures

– Retrospective cohort study is low-cost and quick, e.g., occupational studies

Cohort Study

• Disadvantages– Prospective cohort study is costly and time

consuming

– Loss of subjects from migration, lack of participation, withdrawal and death leads to bias

– Statistically and practically inefficient for rare diseases with long latency

– The exposed may be followed more closely than the unexposed

Example

Measure of Effect• Risk Ratio (Cumulative incidence – risk)• Rate Ratio (Incidence density – rate)

Case-Control Study

• Directionality: Always backwards• Timing: Always Retrospective

Case-Control Study

Examples:

• Case-control studies of aspirin and Reye's syndrome (ActivEpi)

• Case-control study of animal food products and Creutzfeldt-Jakob disease (ActivEpi)

Case-Control Study

Advantages:• Cheaper, quicker

• Sufficient number of cases

• Smaller sample size

• A variety of exposures

Case-Control Study

Disadvantages:• Do not allow several diseases

• Risk of disease cannot be estimated directly

• Selection bias

• Information bias

• Not for rare exposures

Case-Control Study

Selection of Controls• Representative of the source population from which

the cases derived

• Population-based controls -Cases and controls come from the same source population

• Hospital-based controls-Easily accessible, tend to be cooperative, and are inexpensive

-Not usually representative of the source population and may represent an illness caused by the exposure

Case-Control Study

Measure of Effect• Odds Ratio

Cross-Sectional Study

• Directionality: Always Non-directional• Timing: Always Retrospective

Cross-Sectional Study

Advantages:• Convenient and inexpensive

• Can consider several exposures and several diseases

• Can generate hypotheses

• Usually represents the general population

Cross-Sectional Study

Disadvantages:• Cannot establish whether the exposure preceded

disease or disease influenced exposure

• Can identify only prevalent cases rather than incident cases

• Possible bias since only survivors are available for study

• May under-represent diseases with short duration

Cross-Sectional Study

Example:

Cross-Sectional Study of Smoking and Peripheral Vascular Disease (ActivEpi)

Cross-Sectional Study

Measure of Effect• Prevalence ratio (PR)• Prevalence odds ratio (POR)

Hybrid Designs

Combine the elements of at least two basic designs, or extend the strategy of one basic design through repetition.

• The Case-Cohort design• The Nested Case-Control Study

Incomplete Designs

Studies in which information is missing on one or more relevant factors.

• Ecologic Studies• Proportional Studies

References

• ActivEpi Companion Textbook; Kleinbaum, Sullivan, Barker

• Principles of Epidemiology; CDC Self-Study Course

• Epidemiology in Medicine; Hennekens, Buring

• Statistics in Public Health: Quantitative Approaches to Public Health Problems; Stroup, Teutsch

• Case-Control Studies; Schlesselman