Study Design

Study Designs

Descriptive Studies

• Record events, observations or activities,documentaries

• No comparison group or intervention• Describe an event that needs to be brought

to the attention of colleagues• May lead to additional discoveries• Exercise caution with interpretation and application of information

Observational Studies

• Include case-control, cohort (follow-up), and cross-sectional studies

• Goal is to answer questions, not simply describe a situation

• Include a comparison• Report the natural course of events• Researchers are bystanders

Subjects WithSubjects With Disease (case)Disease (case)

Subjects WithoutSubjects WithoutDisease (control)Disease (control)

Study Study PopulationPopulation

Prior Exposure to Prior Exposure to Suspected Risk FactorSuspected Risk Factor

Prior Exposure to Prior Exposure to Suspected Risk FactorSuspected Risk Factor

No Prior Exposure toNo Prior Exposure toSuspected Risk FactorSuspected Risk Factor

No Prior Exposure toNo Prior Exposure toSuspected Risk FactorSuspected Risk Factor

Present-------------Time---------------PastPresent-------------Time---------------Past

Case Control Studies

Case-control Studies:Strengths

• Efficient– Time – Money

• Useful for the study of rare diseases

• Ethical concerns are limited

Case-control Studies:Weaknesses

• Incomplete or biased records• Recall of subjects may be selective or biased• Selection of controls

– From clinic, acute care facility, or community– Who included and excluded– Matched controls

• Selection of cases• Info gathering, differences between groups,

etc.

Subjects ExposedSubjects Exposed

Subjects NotSubjects NotExposedExposed

Study Study SampleSample at Riskat Risk

Develop Measured Develop Measured OutcomeOutcome

Develop MeasuredDevelop MeasuredOutcomeOutcome

Do Not DevelopDo Not DevelopMeasured OutcomeMeasured Outcome

Do Not DevelopDo Not DevelopMeasured OutcomeMeasured Outcome

TimeTime

Cohort Studies

Cohort Studies

• Strengths– Data is collected prospectively and in a more controlled

fashion– Subjects are not required to “recall” data– More accurate assessment of “which” came first

• Weaknesses– High cost and much time required– Population selection– Loss to follow-up– Changes in subject characteristics– Surveillance bias

Case-control study: takes the outcome as the starting point of the inquiry and looks for precursors or risk factors

Cohort Study: starts with a risk factor or exposure and looks at consequences

Comparison Case Control and Cohort

Cross-sectional Studies

• Assesses exposure and outcome status simultaneously

• “Slice-in-time” design or prevalence

• Assessment made during a

single examination

Cross-sectional Studies

Subjects WithSubjects WithDiseaseDisease

Subjects FreeSubjects FreeOf DiseaseOf Disease

Study Study SampleSample

Risk Factor Risk Factor PresentPresent

Risk FactorRisk FactorPresentPresent

No Risk FactorNo Risk FactorPresentPresent

No Risk FactorNo Risk FactorPresentPresent

PRESENTPRESENT

Cross-sectional Studies:

• Evaluate a new test

• Evaluate the predictive capability of clinical features

• Identify etiological agents or causative factors

• Determine prevalence

Cross-sectional Design

• Strengths– Efficient use of time– Efficient use of money

• Weaknesses– Population selection– Subject selection– Antecedent-Consequent relationship

Review : Study Designs

Experimental Studies

• Also known as a controlled trial, clinical trial, health-care trial, or intervention trial

• Goal is to answer questions, not simply describe a situation

• Include a comparison• An intervention is planned• An outcome is measured• Subjects followed forward in time

Definitions

• Retrospective Trial– Case-control study

– A study that analyzes previously collected data

– Carefully kept records are needed

• Prospective Trial:– Cohort or follow-up study

– A study in which data are collected

forward in time from the date

of study initiation

Clinical Trials: Study Design and

Methods of Control.

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Study Designs

The True Experiment

• Clinical trial, controlled trial, health-care trial, intervention trial

• Tool to evaluate clinical problems• Investigator actively intervenes• Intervention applied (independent variable)• Outcome is observed (dependent variable)• Goal is to establish a causal relationship

The True Experiment

• Most effective for controlling extraneous factors affecting interpretation of results

• Limitations include:– Expense– Ethics– Time required– Complexity

The Hypothesis

• Stated in introduction section• Focuses a study• Null hypothesis

– Hypothesis of no difference or no relationship– Results held to be true until evidence shows

otherwise

• Research hypothesis: expected results of the experiment based on theory or related research

The Hypothesis

Two Tailed Hypothesis• States that an

association or difference exists

• No direction of association specified

• Statistically

stronger

One Tailed Hypothesis• States that an

association or difference exists

• Direction between the predictor & outcome variables is specified

• Statistically easier to prove

Subject Identification

• Population selection• Subject selection

– Convenience sample– Systematic sample– Random sample

• Inclusion & exclusion criteria• Author should clearly explain process

of identifying subjects

Methods of Control

• Randomization

• Placebo, active, or historical control

• Blinding

• Stratification

• Matching

• Cross-over design

Randomization

• Always implies there is a control group• Assignment procedure• Improves validity of a study• Subjects are assigned to groups using a

system independent of personal judgment or subjects themselves

• Every member of population has a predetermined probability of being chosen for a group

Randomization

• Goal is to decrease/eliminate selection bias• Individuals randomized may or may not be

representative of a larger population• Differs from random sampling (individuals

are selected for a study by chance from a larger group or population; Aim is to obtain a sample that reflects characteristics of a larger group)

Blinding

• Eliminates bias that randomization cannot eliminate

• Errors occur when patient or individual making assessment are aware of treatment administered, especially if outcome is subjective

• Important to guarantee that the observed outcome is due to the applied therapy

• Attempts to overcome placebo effect

Blinding

• Single blind: subject unaware of therapy received

• Double blind: neither the observer nor subject aware of therapy received

• Triple blind: subject, investigator, and researcher measuring outcome unaware of therapy received

• Often impractical or unsuccessful

Stratification

• Method for dealing with inequalities remaining even with randomization

• Subjects are grouped based on risk factors or co-morbid conditions capable of influencing the results prior to randomization

Matching

• Assignment procedure• Goal is to decrease/eliminate

selection bias• Study and control group are

selected to ensure that an identified variable is the same in both groups

• Ability to evaluate influence of “matched characteristic” on outcome is lost

Cross-over Design

• Uses subjects as their own control• Good for a small number of patients• Subjects assigned to all interventions and

measurements obtained for each treatment• Control for order effect (randomize)• Control for carryover effect

(sufficient wash-out period)• Blind the cross-over point

Cross-over Design

Group 1

Group 2

Group 2

Group 1

Cross-over Point

Tx A

Tx B Tx B

Tx A

Cross-over Design

Group 1

Group 2

Group 2

Group 1

Wash-out Pd

Tx A

Tx B Tx B

Tx A

Case Study

Sample TreatmentMeasureOutcomeVariables

Population

X

One Group Pre-treatment & Post-treatment Design

TreatmentMeasureOutcomeVariables

Population

XSampleMeasureBaselineVariables

Static Group Comparison

Sample

Treatment

Treatment

MeasureOutcomeVariables

MeasureOutcomeVariables

Population

X

Non-equivalent Pre and Post-treatment Control Group

Design

Sample

Treatment

Treatment

MeasureOutcomeVariables

MeasureOutcomeVariables

Population

X

MeasureBaselineVariables

MeasureBaselineVariables

Post-treatment Only Control Group Design

Sample

Treatment

Treatment

MeasureOutcomeVariables

MeasureOutcomeVariables

Population

R

Pre and Post-treatment Control Group Design

Sample

Treatment

Treatment

MeasureOutcomeVariables

MeasureOutcomeVariables

Population

R

MeasureBaselineVariables

MeasureBaselineVariables