Experimental Studies Types of Experimental Studies Multiple experimental

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Experimental Studies

Experimental Studies

Types of Experimental Studies • Multiple experimental groups • Blinds ü single, double, triple

Types of Experimental Studies • Multiple experimental groups • Blinds ü single, double, triple

Public Health & Clinical Objectives • Modify natural history of disease and express disease

Public Health & Clinical Objectives • Modify natural history of disease and express disease prognosis üPrevent or delay death or disability üImprove health of patient or population • Need to use best preventive or therapeutic measures üRandomized 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

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: ücoffee on CHD ücarotene on cancers ühormonal therapy on

Recent Perspectives • Effect of: ücoffee on CHD ücarotene on cancers ühormonal therapy on breast cancer üdrug-lowering cholesterol on CHD

Randomized Trials • Historically, were done accidentally, in other words, “unplanned trials” üAmbroise Pare

Randomized Trials • Historically, were done accidentally, in other words, “unplanned trials” üAmbroise Pare (1510 - 1590) discovered new treatment for war wounds when original therapy was unavailable üJames Lind (1747) studying scurvy • Subjects assigned to groups using a non-biased procedure

Design of a Randomized Clinical Trial

Design of a Randomized Clinical Trial

Selection of Subjects • Well-designed • Eliminate subjectivity • Promote reliability üReplicable, as with

Selection of Subjects • Well-designed • Eliminate subjectivity • Promote reliability üReplicable, as with laboratory experiments üAccurate

Selection of Subjects: Studies without Comparison • Question: If we administer a drug and

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) üData

Selection of Subjects: Studies with Comparison • Historical controls (comparison group from past) üData must be abstracted from records not kept for research purposes üDifferences may be due to quality of the data üMay not be able to substantiate differences üCan be useful for drugs developed against fatal diseases

Selection of Subjects: Studies with Comparison (cont. ) • Simultaneous Non-Randomized Controls ü May

Selection of Subjects: Studies with Comparison (cont. ) • Simultaneous Non-Randomized Controls ü May introduce bias üExample - 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 (cont. ): Randomization • • Best approach Uses tables of random

Selection of Subjects (cont. ): Randomization • • Best approach Uses tables of random numbers Must still eliminate physician bias Can achieve non-predictability

Effect of Comparability Not Randomized

Effect of Comparability Not Randomized

Selection of Subjects (cont. ): Stratified Randomization • Useful when concerned that certain variables

Selection of Subjects (cont. ): Stratified Randomization • Useful when concerned that certain variables may affect the outcome ü For 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

Selection of Subjects (cont. ): Stratified Randomization

Data Collection on Subjects: Potential Variables • Treatment: ü that was assigned ü that

Data Collection on Subjects: Potential Variables • Treatment: ü that was assigned ü that was received • Outcome ü Explicit criteria required ü Comparable measurements required • Prognostic Profile at Entry ü If risk factors for a bad outcome are known, assure that treatment groups are reasonably similar for these factors ü Data for prognostic factors obtained upon enrollment in study • Masking (Blinding)

Data Collection on Subjects (cont. ): Masking (Blinding) • Attempt to eliminate biases &

Data Collection on Subjects (cont. ): Masking (Blinding) • Attempt to eliminate biases & preconceptions • Single-blind ü Subject masking ü Use of placebo • Double-blind ü Subject masking and researcher masking • Data collectors and data analysts • Triple-blind ü Subject masking, researcher masking and study sponsor masking