Unanswered Questions in Schizophrenia Clinical Trials

Abstract

process is carried out varies enormously from one clinical setting to another and from clinical practice to clinical research. In addition, mental health care is fragmented, and records are often poor or not readily obtainable and as a result gathering an accurate history of previous symptoms, course, treatments utilized, and response (either therapeutic oradverse)canbeverydifficult.Patientsarenotgenerally in a position to provide the desired historical details. It is in this context that clinicians make day-to-day decisions as to how to treat their patients. Clinicians will rely on a number of sources of information in developing a treatment plan but will also be influenced by a variety of other factors. It is difficult to rank order these influences; however, personal training and experience, the influence of current colleagues and ‘‘institutional traditions,’’ pharmaceutical detailing and marketing, lectures and continuing medical education activities, journal articles (ranging from reports of individual trials to reviews and meta-analyses) published guidelines, algorithms or expert consensus reports, cost, access, patient preference, and perceived ‘‘hassles’’ are the most salient. It is with this background that we wish to review the role of the clinical trial in providing appropriate influence in this process. The clinical trial is a mainstay of evidenced-based medicine. In psychiatry, we should be particularly sensitive to the need for appropriate strategies to eliminate, or reduce to the extent possible, subjectivity and bias. It is only after well-controlled studies are conducted that we can draw meaningful conclusions about a treatment’s effects. Though unreplicated trials, uncontrolled systematic descriptions, case reports, etc. can be critical in the process of developing new knowledge, the randomized clinical trial provides the most important evidence and remains the gold standard. It is also true that no single trial, no matter how large, can address themultiplequestionsthatmightberelevantinacomplex disease like schizophrenia. In addition, small trials might have insufficient statistical power to allow firm conclusions, but meta-analysis has become an increasingly valuable (though not without its own pitfalls) strategy to combine results from all available trials to provide further critical knowledge on treatment effects and charac