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