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