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A Trial of Clonidine to Stop Smoking

David H. Mark, MD, MPH
JAMA. 1990;263(20):2746. doi:10.1001/jama.1990.03440200048011.
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To the Editor.—  Franks et al1 discuss a point that is increasingly being recognized as a potential flaw in double-blind studies. When medication causes significant side effects, it is not difficult for researchers and patients to figure out which treatment is being administered. For researchers, this can cause bias in ascertainment of certain outcomes. For patients, this defeats the whole purpose of giving the placebo, which is to rule out a placebo effect. Thus, estimates of the effectiveness of drugs are inflated by the amount of the placebo effect, which would be absent in patients who believe they are taking a placebo.Other researchers have suggested possible strategies for dealing with this problem.2,3 Placebos that mimic the side effects of the active treatment are one option. This will decrease the ability of the patients to guess correctly which medication they are taking. However, patients are still aware that


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