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Epidemiologic Study Epidemiologic Study DesignsDesigns
Acknowledgements:
M. Tevfik DORAK
Ahmed MandilAhmed 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
DescriptiveAnalytical
Case-Control Cohort+ cross-sectional & ecologic
(RCTs)
Descriptive studiesDescriptive studies
Examine patterns of disease
Analytical studiesAnalytical studies
Studies of suspected causes of diseases
Experimental studiesExperimental studies
Compare treatment modalities
Epidemiologic Study Designs
Epidemiologic Study Designs
Grimes & Schulz, 2002
Hierarchy of Epidemiologic Study DesignHierarchy of Epidemiologic Study Design
Tower & Spector, 2007
ObservationalObservational Studies 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?
the profile of a single patient is reported in detail by one or more clinicians
• Example
In 1961, a published case report of a 40 year-old women who developed pulmonary embolism after beginning use oral contraceptive
Case Series• What?
An individual case report that has been expanded to include a number of patients with a given disease
• Example
In Los Angeles, five young homosexuals men, previously healthy, were 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
AnalyticalAnalytical Studies 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)
PopulationPeople without disease
Exposed
Not exposed
Disease
No disease
Disease
No disease
Cohort StudiesCohort Studies
Coh
ort D
esig
n
time
Study begins here
Studypopulation
free ofdisease
Factorpresent
Factorabsent
disease
no disease
disease
no disease
presentfuture
Examples of Cohort StudiesExamples of Cohort Studies
*Framingham Heart Study (www)
* Physicians' Health Study (www)
* Nurses' Health Study (www)
Advantages of Cohort StudiesAdvantages 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 StudiesDisadvantages 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
Population Cases (follow up 2 years)
HIV + 215 8HIV - 289 1
Presentation of cohort data: Presentation of cohort data: Population at riskPopulation at risk
Does HIV infection increase risk of developing TB among a population of drug users?
Source: Selwyn et al., New York, 1989EPIET
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
Exposure Population (f/u 2 years)
Cases Incidence
(%) Relative
Risk
HIV +
215
8
3.7
12.3
HIV - 298 1 0.3
Does HIV infection increase risk of developing TB Does HIV infection increase risk of developing TB among drug users?among drug users?
EPIET
time
Exposure Study startsDisease
occurrence
Prospective cohort studyProspective cohort study
time
ExposureStudy startsDisease
occurrence
EPIET
Retrospective cohort studiesRetrospective cohort studies
Exposure
time
Diseaseoccurrence Study starts
EPIET
Cohort StudiesCohort Studies
Grimes & Schulz, 2002
Population
Cases
Controls
Exposed
Case-Control StudiesCase-Control Studies
Not exposed
Exposed
Not exposed
Case-Control StudiesCase-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 StudiesAdvantages 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 StudiesDisadvantages 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 StudiesCase-Control Studies: :
Potential BiasPotential 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.
Outcome
Risk factor
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 StudiesAdvantages
• Cheap and quick studies.
• Data is frequently available through current records or statistics.
• Ideal for generating new hypothesis.
Cross-Sectional StudiesDisadvantages
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 Study
Alternative Name
Unit of Study
Randomised Controlled Trials
Field Trials
Community Trials
Clinical Trials
Community Intervention Studies
Patients
Healthy People
Communities
Types of trials
B lind ed N o t b lind ed
R a nd o m ised N o t ran d om ised
C o n tro lled N o t co n tro lled
T ria l
Exp
erim
enta
l Des
ign
timeStudy begins here (baseline point)
Studypopulation
Intervention
Control
outcome
no outcome
outcome
no outcome
baselinefuture
RANDOMIZATION
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