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Experimental Studies
Types of Experimental Studies
• Multiple experimental groups
• Blinds single, double, triple
Public Health & Clinical Objectives
• Modify natural history of disease and express disease prognosis Prevent or delay death or disabilityImprove health of patient or population
• Need to use best preventive or therapeutic measuresRandomized trials are ideal design to
evaluate effectiveness and side effects of new forms of intervention
Historical Perspectives
• Sir Francis Galton (1883) - ruminated over the influence of prayer
• Joyce and Welldon (1965) found no benefit of prayer
• R. C. Byrd (1988) - suggested positive benefits
• Washington Post Parade article (2003) - also suggested positive benefits
Recent Perspectives
• Effect of: coffee on CHDcarotene on cancershormonal therapy on breast cancerdrug-lowering cholesterol on CHD
Randomized Trials
• Historically, were done accidentally, in other words, “unplanned trials”Ambroise Pare (1510 - 1590) discovered
new treatment for war wounds when original therapy was unavailable
James Lind (1747) studying scurvy
• Subjects assigned to groups using a non-biased procedure
Design of a Randomized Clinical Trial
Selection of Subjects
• Well-designed
• Eliminate subjectivity
• Promote reliabilityReplicable, as with laboratory
experimentsAccurate
Selection of Subjects: Studies without Comparison
• Question: If we administer a drug and the patient improves, can we attribute the improvement to the administration of that drug?
• Answer: Results can always be improved by omitting controls.
- Prof. Hugo Muensch Harvard University
Selection of Subjects: Studies with Comparison
• Historical controls (comparison group from past)Data must be abstracted from records not
kept for research purposesDifferences may be due to quality of the dataMay not be able to substantiate differencesCan be useful for drugs developed against
fatal diseases
• Simultaneous Non-Randomized Controls May introduce biasExample - BCG vaccination study in NYC in
1975 • Investigators introduced selection bias in the
experimental group and controls• A change in the study design that eliminated
selection bias, although still not randomized, also eliminated differences observed in final results
Selection of Subjects: Studies with Comparison (cont.)
• Best approach
• Uses tables of random numbers
• Must still eliminate physician bias
• Can achieve non-predictability
Selection of Subjects (cont.):
Randomization
Effect of Comparability
Not Randomized Randomized
Selection of Subjects (cont.):
Stratified Randomization• Useful when concerned that certain
variables may affect the outcomeFor example, when the prognosis may be
much worse for older patients • Want two treatment groups to be
comparable in terms of the variables of concern
• Initially stratify (layer) the study population according to each variable of concern and then randomize participants to treatment groups within each stratum
Selection of Subjects (cont.):
Stratified Randomization
Data Collection on Subjects:Potential Variables
• Treatment: that was assigned that was received
• OutcomeExplicit criteria requiredComparable measurements required
• Prognostic Profile at Entry If risk factors for a bad outcome are known,
assure that treatment groups are reasonably similar for these factors
Data for prognostic factors obtained upon enrollment in study
• Masking (Blinding)
Data Collection on Subjects (cont.):
Masking (Blinding)
• Attempt to eliminate biases & preconceptions• Single-blind
Subject masking Use of placebo
• Double-blindSubject masking and researcher masking
• Data collectors and data analysts
• Triple-blindSubject masking, researcher masking and study
sponsor masking