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One group is given a newly developed medication X, and the other group placebo. If X has noticeable side effects, like extra sleepiness, change in appetite, tremors, etc, wouldn't the participates in group 1 realize that they're given the real medication? How would it affect the study?

asmani
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    not necessarily: even placebo has "noticeable" side effects. every symptom you describe can also occur in a placebo group. under some circumstances, it could be an issue. if it is, then they would consider using an active placebo. this is uncommon, however. you can test for what you're describing: you ask the participants what group they were in. a properly-blinded study will have the same rate of wrong/correct belief. – faustus Feb 12 '18 at 11:48

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If a drug produces noticeable side effects, it is likely that studies will suffer from an unblinding effect which will cause overstatement of efficacy of the drug. This is because in a properly blinded study, the placebo effect is the same* for both the active drug and the placebo, so we can calculate the true efficacy by subtracting*. Unblinding causes the placebo effect to increase in the treatment group (due to increased certainty that they're receiving the active drug).

Active placebos could be used to mimic side effects and reduce risk of unblinding. Antidepressants, for example, show reduced effect in studies that use an active placebo.

Surveys could be done of patient and provider so you could verify the validity of the blinding using the correlation between the patient taking the drug and belief that the patient is taking the drug.

Neither of those things are commonly done.

Zaz
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