A controlled trial comparing three hynotic drugs— chloral betaine, 750 mg; diphenhydramine hydrochloride, 50 mg; pentobarbital, 100 mg—and a placebo was introduced into a comprehensive drug surveillance program. The standard methods of data collection employed in the program were applied to the trial. These methods employ judgments made by the attending physicians on the efficacy and side effects of drugs. The greater efficacy of hypnotics was evident in the data. There was also some evidence of a higher frequency of side effects among patients who received hypnotic drugs. The efficacy of the placebo was greater among women than among men while the hypnotic drugs were equally effective among both sexes. It is concluded that physicians' judgments of efficacy and side effects are valid to the extent of permitting the demonstration of differences between hypnotic drugs and the placebo, under the conditions of a randomized, double-blind trial.
Jick H, Slone D, Shapiro S, Lewis GP. Clinical Effects of HypnoticsI. A Controlled Trial. JAMA. 1969;209(13):2013–2015. doi:10.1001/jama.1969.03160260017004