How and why study designs affect the nature and validity of study results: appearance versus true knowledge. Part I

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.