COLUMNS: PSYCHOPHARMACOLOGYHow and Why Study Designs Affect the Nature and Validity of Study Results: Appearance Versus True Knowledge. Part IPreskorn, Sheldon H. MDAuthor Information Professor, Department of Psychiatry, University of Kansas School of Medicine-Wichita, and Chief Executive Officer and Medical Director, Clinical Research Institute, Wichita, Kansas He has more than 30 years of drug development research experience at all levels (ie, pre-clinical through Phase IV) and has been a principal investigator on over 250 clinical trials including every antidepressant marketed in the United States over the last 25 years. Dr Preskorn maintains a website at (www.preskorn.com) where readers can access previous columns and other publications. This two-part series of columns is adapted from Preskorn SH. The appearance of knowledge. Journal of Practical Psychiatry and Behavioral Health 1997;3:233-8. Disclosure statement: Dr Preskorn, as chief executive officer of the Clinical Research Institute, Wichita, KS, and, in many cases, as principal investigator, has received grants from the following entities: AstraZeneca, Biovail, Boehringer-Ingelheim, Bristol-Myers Squibb, CoMentis, Cyberonics, Dainippon Sumitomo, Eisai, EnViVo, GlaxoSmithKline, Merck, Memory, Organon, Otsuka, Pfizer, Sepracor, Somerset, Wyeth, and the National Institute of Mental Health. He has served as a consultant, on the advisory board, and/or as a speaker for the following: Biovail, Bristol-Myers Squibb, CoMentis, Covedien, Cyberonics, Dainippon Sumitomo, Eli Lilly, EnViVo, Evotec, Fabre-Kramer, Jazz, Lundbeck, Memory, Organon, Pfizer, Somerset, Takeda, Transcept, and Wyeth. Journal of Psychiatric Practice: July 2009 - Volume 15 - Issue 4 - p 306-310 doi: 10.1097/01.pra.0000358316.96555.f2 Buy Metrics Abstract Patients often do not respond optimally to the first medication tried so that switching among classes of medications—and even within a class—for a given indication is a common clinical practice. In the absence of data, such switches are often based on clinical judgment or experience, but when data are available, that is generally considered preferable. However, such data may be derived from sub-optimally designed trials that produce only the appearance of knowledge. In this first of a two-part series, findings from sequential treatment trials of selective serotonin reuptake inhibitors (SSRIs) are used to illustrate how such research is done and factors that can affect outcomes. Results of early trials suggested that 50%–60% of patients who did not benefit from one SSRI could benefit when switched to a second SSRI, a finding not supported by pharmacologic data nor recent research. Differences between treatment in clinical trials and routine practice that may account for discrepancies between those early results and pharmacologic data are discussed. Part II of this series will describe study designs, from the least to the most rigorous, to help clinicians recognize when studies are providing the appearance rather than the substance of knowledge. (Journal of Psychiatric Practice 2009;15:306-310). Copyright © 2009 Wolters Kluwer Health, Inc. All rights reserved.