The Need for Transparency of Clinical Trials Jeffrey Bridge, The Research Institute at Nationwide Children's Hospital 24 November 2008 The article by Dr. Ioannidis provides a thought-provoking discussion of two recently published meta-analyses—the results of which call into question the apparent efficacy of antidepressant medications—and offers some practical suggestions for ways to improve the evidence base for antidepressants going forward: pre-registration of fully transparent protocols, strict adherence to a priori defined data analysis plans, and public availability of individual patient-level trial data for prospective meta-analyses. The use of “mega-trials” to answer pressing questions about the clinical utility of antidepressant medications is also an attractive proposition as these types of studies use randomization to avoid selection bias, simple designs to reduce investigator and participant burden, and enroll thousands of participants from diverse clinical practice settings, which increases generalizability and provides ample statistical power to identify small but clinically important treatment effects.1, 2With regard to the issue of transparency, I would like to draw attention to the recently enacted FDA Amendments Act (Public Law 110-85), which mandates registration and results of all controlled, clinical trials other than Phase I investigations.3 This law requires that sponsors and investigators report basic trial results, including demographic and baseline characteristics of the study participants, the number of participants who dropped out or were excluded, and provide tables of values for the primary and secondary efficacy outcome measures as well as serious adverse events (SAEs) and frequent adverse events in each arm of the trial, including statistical significance.4 Although still a long way from achieving the goal of full access to individual patient trial data, the FDA Amendments Act may bring us one step closer to understanding the true benefit-to-risk profile of all medications, including antidepressants.REFERENCES1. March JS, Silva SG, Compton S, Shapiro M, Califf R, Krishnan R. The case for practical clinical trials in psychiatry. Am J Psychiatry. May 2005;162(5):836-846.2. Peto R, Collins R, Gray R. Large-scale randomized evidence: large, simple trials and overviews of trials. J Clin Epidemiol. Jan 1995;48(1):23-40.3. U.S. Food and Drug Administration. Law Strengthens FDA. http://www.fda.gov/oc/initiatives/advance/fdaaa.html (accessed 11/14/2008).4. Zarin DA, Tse T. Medicine. Moving toward transparency of clinical trials. Science. Mar 7 2008;319(5868):1340-1342. Competing interests None declared.