The treatment of schizophrenia represents one of the most difficult areas of medicine for carrying out reliable
and informative clinical trials of new medicinal products. The methodological issues that affect studies of neuroleptic agents are not unique. The evaluation of treatments for negative symptoms probably represents the most, unusual methodological problem (not covered in this paper), but from a statistical perspective this problem has parallels elsewhere in medicine. The real reason why clinical trials in schizophrenia are so difficult, is the fact that a number of methodological issues Inhibitors,research,lifescience,medical are present, together and in a severe form. This paper is concerned largely with trials that provide the confirmatory evidence of the efficacy of new medicinal agents, that, is those carried out during their phase 3 development, or perhaps during the development of a new indication in Inhibitors,research,lifescience,medical phase 4. Hence, it is concerned only with controlled trials that provide the most reliable and informative
evidence of efficacy Inhibitors,research,lifescience,medical for licensing decisions. General guidance on the statistical issues that arise in confirmatory trials and that relate to regulatory decisions can be found in ICH E9 (ICH, International Conference on Harmonization of Technical Requirements for Registration Inhibitors,research,lifescience,medical of Pharmaceuticals for Human Use).1 Guidance on the design, conduct, analysis, and interpretation of these trials in the field of schizophrenia can be found in the Committee for Proprietary Medicinal Products (CPMP) Note for guidance.2 Two issues require a broader introduction before discussing their impact, on trials in schizophrenia. The
Inhibitors,research,lifescience,medical first is the use of placebo. TTic most recent revision of the Declaration of Helsinki3 in October 2000 Dipeptidyl peptidase caused alarm among those conducting and carrying out controlled clinical trials by appearing to limit the future role of placebo to a serious extent. The use of placebo in schizophrenia trials was already a problematic matter. Hence in the context of this paper, it is important to check details clarify the basis of the concerns surrounding its use and to explain the current resolution. The second issue is the design of studies to evaluate the long-term maintenance treatment of an episodic, or partly episodic, condition. The use of medicinal products for this purpose arises in a number of psychiatric and other indications, and a terminology has been developed to communicate thoughts and conclusions.