Clinical evaluation of hypnotic drugs: contributions from sleep laboratory studies.

The most thorough and clinically relevant approach to hypnotic drug evaluation is one that balances the strengths and weaknesses of clinical trials and sleep laboratory evaluations. Advantages of clinical trials include the ability to evaluate large numbers of subjects and specific target groups and to thoroughly assess and quantify a drug's side effects, whereas sleep laboratory studies are very limited in all of these areas. Sleep laboratory studies however provide a rigorous, precise, and comprehensive profile of a drug's activity since there is more control over experimental variables and measurements are objective as well as continuous throughout the night. These benefits offset the shortcomings of clinical trials, which include a lack of objective measurements, less control over experimental variables, failure to evaluate a drug's effectiveness with continued use, and inattention to drug interaction and withdrawal effect. Several basic principles derived from sleep laboratory findings have been incorporated into both the clinical trials and sleep laboratory evaluations recommended in the new FDA Guidelines for the Clinical Evaluation of Hypnotic Drugs. These principles include provision for adequate baseline and withdrawal periods, use of multiple consecutive drug nights to assess a drug's effectiveness with continued use, and inclusion of an adequate washout period when a cross-over design is used. The guidelines do not emphasize either clinical trials or sleep laboratory studies at the expense of each other, but rather stress their complementary utilization.