Study Designs in Epidemiologic
Research
Fundamental Assumption in Epidemiology
• Disease doesn’t occur in a vacuum
Disease is not randomly distributed
throughout a population
• Epidemiology uses systematic approach to
study the differences in disease distribution
in subgroups
• Allows for study of causal and preventive
factors
Components of Epidemiology
• Measure disease frequency
• Quantify disease
• Assess distribution of disease
• Who is getting disease?
• Where is disease occurring?
• When is disease occurring?
➔Formulation of hypotheses concerning causal and
preventive factors
• Identify determinants of disease
• Hypotheses are tested using epidemiologic studies
Types of Primary Studies
• Descriptive studies
• describe occurrence of outcome
• Analytic studies
• describe association between
exposure and outcome
Basic Question in Analytic Epidemiology
• Are exposure and disease linked?
Exposure Disease
Basic Questions in Analytic Epidemiology
• Look to link exposure and disease
• What is the exposure?
• Who are the exposed?
• What are the potential health effects?
• What approach will you take to study
the relationship between exposure
and effect?
Basic Research Study
Designs and their
Application to Epidemiology
Major Goal
• To prevent and control disease
• In a coordinated plan, try to
• identify hypotheses on what is related
to disease and may be causing it
• formally test these hypotheses
•Study designs direct how the
investigation is conducted
What designs exist to identify
and investigate factors in
disease?
Descriptive Analytic
Case report Cohort study
RCT
Case series Case-Control
study
Descriptive
Epidemiology Case-Crossover
study
Cross-sectional
study
Before-After
study
Ecologic study
Time frame of Studies
• Prospective Study - moves forward,
looks to the future, examines future
events, follows a condition, concern or
disease into the future
time
Study begins here
Time frame of Studies
• Retrospective Study - “to look back”,
looks back in time to study events that
have already occurred
time
Study begins here
Study Design Sequence
Hypothesis formation
Descriptive
Case reports Case series
epidemiology
Analytic Animal Lab
epidemiology study study
Clinical
trials Hypothesis testing
Cohort Case- Cross-
control sectional
Descriptive Studies Develop
hypothesis
Increasing Knowledge of
Disease/Exposure Investigate it’s
Case-control Studies relationship to
outcomes
Define it’s meaning
Cohort Studies with exposures
Test link
Clinical trials experimentally
Descriptive Studies
Case Reports
• Detailed presentation of a single case or
handful of cases
• Generally report a new or unique finding
• e.g. previously undescribed disease
• e.g. unexpected link between diseases
• e.g. unexpected new therapeutic effect
• e.g. adverse events
Case Series
• Experience of a group of patients with a similar
diagnosis
• Assesses prevalent disease
• Cases may be identified from a single or
multiple sources
• Generally report on new/unique condition
• May be only realistic design for rare disorders
Case Series
• Advantages
• Useful for hypothesis generation
• Informative for very rare disease with few
established risk factors
• Characterizes averages for disorder
• Disadvantages
• Cannot study cause and effect relationships
• Cannot assess disease frequency
Case Report One case of unusual
findings
Multiple cases of
Case Series unusual findings
Descriptive Population-based
Epidemiology Study cases with denominator
Analytical Studies
Study Designs - Analytic Epidemiology
• Experimental Studies
• Randomized controlled clinical trials (RCT)
• Community trials
• Observational Studies
• Group data
• Ecologic
• Individual data
• Cross-sectional
• Cohort
• Case-control
• Case-crossover
Experimental Studies
• Treatment and exposures occur in a
“controlled” environment
• Planned research designs
• Clinical trials are the most well known
experimental design. Clinical trials use
randomly assigned data.
• Community trials use non-random data
Observational Studies
• Non-experimental
• Observational because there is no human
intervention
• Treatment and exposures occur in a “non-
controlled” environment
• Individuals can be observed prospectively,
retrospectively, or currently
Cross-sectional studies
• An “observational” design that surveys exposures
and disease status at a single point in time (a cross-
section of the population)
time
Study only exists at this point in time
Cross-sectional Design
factor present
No Disease
factor absent
Study
population
factor present
Disease
factor absent
time
Study only exists at this point in time
Cross-Sectional Studies
• Exposure and outcome status are determined at
the same time
• Examples include:
– Behavioral Risk Factor Surveillance System
(BRFSS) - [Link]
– National Health and Nutrition Surveys (NHANES)
- [Link]
• Also include most opinion and political polls
28
Cross-sectional Studies
• Often used to study conditions that are relatively frequent
with long duration of expression (non-fatal, chronic
conditions)
• It measures prevalence, not incidence of disease
• Example: community surveys
• Not suitable for studying rare or highly fatal diseases or a
disease with short duration of expression
Cross-sectional studies - Strengths
• Useful baseline assessment
• Generalizable results if population based sample
• Study multiple outcomes and exposures
• Immediate outcome assessment and no loss to follow-
up, therefore faster, cheaper, easier
• Hypothesis generating for causal links
• Serial surveys eg, Census
30
Cross-sectional studies
• Disadvantages
• Weakest observational design, (it measures
prevalence, not incidence of disease). Prevalent
cases are survivors
• The temporal sequence of exposure and effect may
be difficult or impossible to determine
• Usually don’t know when disease occurred
• Rare events a problem. Quickly emerging diseases
a problem
Epidemiologic Study Designs
• Case-Control Studies
• an “observational” design comparing
exposures in disease cases vs. healthy
controls from same population
• exposure data collected retrospectively
• most feasible design where disease
outcomes are rare
Case-Control Studies
Cases: Disease
Controls: No disease
factor present
Cases
factor absent (disease)
Study
population
factor present Controls
(no disease)
factor absent
present
past
time
Study begins here
Case-Control Study
• Strengths
• Less expensive and time consuming
• Efficient for studying rare diseases
• Limitations
• Inappropriate when disease outcome for a specific
exposure is not known at start of study
• Exposure measurements taken after disease occurrence
• Disease status can influence selection of subjects
Hypothesis Testing: Case-Crossover Studies
• Study of “triggers” within an individual
• ”Case" and "control" component, but information of both
components will come from the same individual
• ”Case component" = hazard period which is the time
period right before the disease or event onset
• ”Control component" = control period which is a
specified time interval other than the hazard period
Epidemiologic Study Designs
• Cohort Studies
• an “observational” design comparing
individuals with a known risk factor or
exposure with others without the risk factor or
exposure
• looking for a difference in the risk (incidence) of
a disease over time
• best observational design
• data usually collected prospectively (some
retrospective)
disease
Factor
Study present no disease
population
free of
disease Factor disease
absent
no disease
present
future
time
Study begins here
Time frame of Studies
• Prospective Study - moves forward, looks to the
future, examines future events, follows a
condition, concern or disease into the future
time
Study begins here
Prospective Cohort study
Exposed Outcome
Measure exposure
and confounder
variables
Baseline Non-exposed Outcome
time
Study begins here
Time frame of Studies
• Retrospective Study - “to look back”, looks back
in time to study events that have already
occurred
time
Study begins here
Retrospective Cohort study
Exposed Outcome
Measure exposure
and confounder
variables
Baseline Non-exposed Outcome
time
Study begins here
Differentiating between Prospective and Retrospective
• Prospective cohort study: Investigator starts the study
(from the beginning) with the identification of the
population and the exposure status (exposed/not exposed
groups)
• Follows them (over time) for the development of disease
• Takes a relatively long time to complete the study (as long
as the length of the study)
Differentiating between Prospective and Retrospective
• Retrospective cohort study: Investigator uses existing data
collected in the past to identify the population and the
exposure status (exposed/not exposed groups)
• Determines at present the (development) status of disease
• Investigator spends a relatively short time to assemble study
population (and the exposed/not exposed groups) from past
data
• Determine disease status at the present time (no future follow-
up)
Cohort Study
• Strengths
• Exposure status determined before disease detection
• Subjects selected before disease detection
• Can study several outcomes for each exposure
• Limitations
• Expensive and time-consuming
• Inefficient for rare diseases or diseases with long latency
• Loss to follow-up
Cohort versus Case-Control Study
47
Classification of Study Designs
48
Source: Grimes DA, Schulz KF. Lancet 2002; 359: 58
Experimental Studies
• Investigator can “control” the exposure
• Similar to laboratory experiments except living
populations are the subjects
• Generally involves random assignment to groups
• Clinical trials are the most well known experimental
design
• The ultimate step in testing causal hypotheses
Experimental Studies
• In an experiment, we are interested in the
consequences of some treatment on some outcome.
• The subjects in the study who actually receive the
treatment of interest are called the treatment group.
• The subjects in the study who receive no treatment
(placebo) or a different treatment are called the
comparison group.
Epidemiologic Study Designs
• Randomized Controlled Trials (RCTs)
• a design with subjects randomly assigned to
“treatment” and “comparison” groups
• provides most convincing evidence of relationship
between exposure and effect
• not possible to use RCTs to test effects of exposures
that are expected to be harmful, for ethical reasons
RANDOMIZATION outcome
Intervention
no outcome
Study
population
outcome
Control
no outcome
baseline
future
time
Study begins here (baseline point)
Epidemiologic Study Designs
• Randomized Controlled Trials (RCTs)
• the “gold standard” of research designs
• provides most convincing evidence of
relationship between exposure and effect
• trials of hormone replacement therapy in
menopausal women found no protection for heart
disease, contradicting findings of prior
observational studies
Randomized Controlled Trials
• Disadvantages
• Very expensive
• Not appropriate to answer certain types of
questions
• it may be unethical, for example, to assign
persons to certain treatment or comparison
groups
