Epidemiologic Study

Designs

Acknowledgements:
M. Tevfik DORAK
Ahmed Mandil
Kimberly R. Barber
Birgit Greiner
 Study design: Definition
A study design is a specific plan or
protocol for conducting the study,
which allows the investigator to
translate the conceptual hypothesis into
an operational one.
 Epidemiologic Study Designs

Experimental Observational
(RCTs)

Analytical Descriptive

Case-Control Cohort
+ cross-sectional & ecologic
Epidemiologic Study Designs

Descriptive studies
Examine patterns of disease

Analytical studies
Studies of suspected causes of diseases

Experimental studies
Compare treatment modalities
Epidemiologic Study Designs

Grimes & Schulz, 2002

Hierarchy of Epidemiologic Study Design

Tower & Spector, 2007

 Observational Studies
(no control over the circumstances)
- Descriptive: Most basic demographic studies
* Case Report
* Case Series
* Cross sectional
* Ecological/Correlation study
- Analytical: Comparative studies testing an hypothesis
* cross-sectional
(a snapshot; no idea on cause-and-effect relationship)
* cohort
(prospective; cause-and-effect relationship can be inferred)
* case-control
(retrospective; cause-and-effect relationship can be inferred)
Epidemiologic Study Designs

Grimes & Schulz, 2002

 Case Report
• What? • Example
the profile of a single In 1961, a published
patient is reported in case report of a 40
detail by one or more year-old women who
clinicians developed pulmonary
embolism after
beginning use oral
contraceptive
 Case Series
• What? • Example
An individual case In Los Angeles, five
report that has been young homosexuals
expanded to include a men, previously
number of patients healthy, were
with a given disease diagnosed with
pneumocyst cariini
pneumonia in a 6-
month period
 Ecological or Correlation
• Ecological Studies
– whole population is the unit of analysis
– relationship between exposure and outcome at the
individual level is missing (incomplete design)
– ecological fallacy
 Analytical Studies
(comparative studies testing an hypothesis)

* cohort (prospective)
Begins with an exposure (smokers and non-smokers)

* case-control (retrospective)
Begins with outcome (cancer cases and healthy controls)
 Cohort Studies

Disease
People Exposed No disease
Population without
disease Not Disease
exposed
No disease
 disease
Factor
present
Study no disease
population
Cohort Design

free of
disease disease
Factor
absent
no disease

present
future

time
Study begins here
Examples of Cohort Studies

*Framingham Heart Study (www)

* Physicians' Health Study (www)
* Nurses' Health Study (www)
 Advantages of Cohort Studies

- Can establish population-based incidence

- Accurate relative risk (risk ratio) estimation
- Can examine rare exposures (asbestos > lung cancer)
- Temporal relationship can be inferred (prospective design)
- Time-to-event analysis is possible
- Can be used where randomization is not possible
- Magnitude of a risk factor’s effect can be quantified
- Selection and information biases are decreased
- Multiple outcomes can be studied
(smoking > lung cancer, COPD, larynx cancer)
 Disadvantages of Cohort Studies

- Lengthy and expensive

- May require very large samples
- Not suitable for rare diseases
- Not suitable for diseases with long-latency
- Unexpected environmental changes may influence the association
- Nonresponse, migration and loss-to-follow-up biases
- Sampling, ascertainment and observer biases are still possible
 Presentation of cohort data:
Population at risk

Does HIV infection increase risk of developing TB

among a population of drug users?

Population Cases
(follow up 2 years)

HIV + 215 8
HIV - 289 1

Source: Selwyn et al., New York, 1989

EPIET
 Relative Risk calculation
Disease Un-disease
Expose a b a+b
Un-expose c d c+d
Incidence in expose (Ie)=a/a+b
Incidence in unexpose (Io)=c/c+d
Relative Risk=Ie/Io
 Does HIV infection increase risk of developing TB
among drug users?

Population Incidence Relative

Exposure Cases
(f/u 2 years) (%) Risk

HIV + 215 8 3.7 12.3

HIV - 298 1 0.3

EPIET
 Prospective cohort study

Disease
Exposure Study starts occurrence

time

Disease
Study starts Exposure occurrence

time
EPIET
 Retrospective cohort studies

Disease
Exposure Study starts
occurrence

time

EPIET
Cohort Studies

Grimes & Schulz, 2002

 Case-Control Studies

Exposed
Not
Cases
exposed
Population
Exposed Controls
Not
exposed
Case-Control Studies

Schulz & Grimes, 2002

 Odds ratio calculation
Case Control
Expose a b
Un-expose c d

Odds Ratio =ad/bc

 Advantages of Case-Control Studies

- Cheap, easy and quick studies

- Multiple exposures can be examined
- Rare diseases and diseases with long latency
can be studied
- Suitable when randomization is unethical
(alcohol and pregnancy outcome)
 Disadvantages of Case-Control Studies

- Case and control selection troublesome

- Subject to bias (selection, recall, misclassification)
- Direct incidence estimation is not possible
- Temporal relationship is not clear
- Multiple outcomes cannot be studied
-If the incidence of exposure is high, it is difficult to show the
difference between cases and controls
-Reverse causation is a problem in interpretation
Case-Control Studies:
Potential Bias

Schulz & Grimes, 2002

 Application Exercise:
Case / Control Study
• Describe a case/control study on the
relationship between childhood obesity,
smoking history, and occurrence of
hypertension in middle-aged men.

• What research question can we answer?

 Cross-Sectional Studies
• Measurement of risk and outcome at the
same time.
Risk factor

Outcome
Cross-Sectional Design
• The only study
capable of calculating
prevalence.
– Proportion of the
population with
the outcome at
any point in time.
 Application Exercise:
Cross-Sectional Study
• Design a cross-sectional study that
examines the relationship between dietary
sodium and hypertension in middle-aged
men.

• What research question can we answer?

 Cross-Sectional Studies
Advantages

• Cheap and quick studies.

• Data is frequently available through current
records or statistics.
• Ideal for generating new hypothesis.
 Cross-Sectional Studies
Disadvantages
The importance of the relationship between
the cause and the effect cannot be
determined.
• Temporal weakness:
– Cannot determine if cause preceded the effect
or the effect was responsible for the cause.
– The rules of contributory cause cannot be
fulfilled.
 Type of Alternative Unit of
Study Name Study
Randomised Controlled Clinical Trials Patients
Trials

Field Trials Healthy People

Community
Community Trials Intervention Studies Communities
 Types of trials
T r ia l

C o n tr o lle d N o t c o n tr o lle d

R a n d o m is e d N o t r a n d o m is e d

B lin d e d N o t b lin d e d
 RANDOMIZATION outcome
Intervention
Experimental Design
no outcome
Study
population
outcome
Control
no outcome
baseline
future

time
Study begins here (baseline point)
Intervention Randomisation

Control Blinding
 Experimental studies are useful
for evaluating:
• New drug or other treatment for disease
• New medical/health care technology
• Methods of prevention
• Methods of health promotion
• New health protection policies
• Programs for screening and diagnosis
• Methods of providing health care
• New health care policies
 Ethical Considerations in
experimental studies
• Is proposed treatment safe?
• For the sake of trial, can a treatment ethically
be withheld?
• What patients may be brought into trial and
allocated randomly to treatments?
• Is it ethical to use a placebo or dummy
treatment?
• Is it proper for the trial to be in any way
masked?
Adapted from Hill (1977)
 Advantages (I)

– the “gold standard” of research designs.

They thus provide the most convincing
evidence of relationship between
exposure and effect. Example:
• trials of hormone replacement therapy in
menopausal women found no protection
for heart disease, contradicting findings
of prior observational studies
 Advantages (II)

• Best evidence study design

• No selection bias (using blinding)
• Controlling for possible confounders
• Comparable Groups (using
randomization)
 Disadvantages
• Is the most expensive study design in terms
of money, time, and number of patients.
– Issues of patient attrition and compliance may
invalidate the results.
– Can be problematic for ethical reasons.
• Use of placebo
• Harm outweighing benefits
• Zero tolerance for some exposures