TY - JOUR T1 - Successful Trial Design and Planning in Systemic Sclerosis: Does It Take a Village? JF - The Journal of Rheumatology JO - J Rheumatol SP - 297 LP - 299 DO - 10.3899/jrheum.180062 VL - 45 IS - 3 AU - LESLEY ANN SAKETKOO Y1 - 2018/03/01 UR - http://www.jrheum.org/content/45/3/297.abstract N2 - Negative trial reporting, especially in rare diseases, provides essential information. The design and analysis of a “negative” trial, in diseases for which few potential treatments and no cure exist, warrants particular scrutiny to determine whether the trial was truly negative, or rather a “failed” trial owing to other design, financial, planning, or recruitment impediments1. A trial that is discontinued early warrants the label negative if an unbiased, independent data safety monitoring board identified either a harm signal (excessive intolerance or drug-related adverse events) or a clear worsening of the disease state in comparison to placebo.In an article by Hsu, et al, in this issue of The Journal, the authors describe a 52-week randomized double-blind placebo-controlled multicenter phase II study of pomalidomide2. The sponsors have conceded to the reviewers that the study was discontinued early because of poor recruitment. Yet the article’s discussion section persists in stating that discontinuation by the sponsor was due to lack of drug efficacy. To be clear, there exists no statistical application capable of calculating a reliable result in any of the study variables between the 4 treatment and the 7 placebo cases completing a study that was powered for a sample of 88. Thus, the study results carry similar statistical weight to the initial anecdotal case reports of perceived efficacy of pomalidomide by systemic sclerosis (SSc) specialists — cases that likely inspired moving the drug to trial.SSc disease behavior remains complex and challenging to the most seasoned SSc clinician researchers who are well-acclimated to a cautious approach to data interpretation in this “rare” and exceptionally complex disease. In a journal less cognizant of the humbling landscape in SSc clinical trial design, this study would have slipped by as a negative study, generating an inaccurate interpretation of the … Address correspondence to Dr. L.A. Saketkoo, MD, MPH, Associate Professor of Medicine, Tulane University School of Medicine, Division of Pulmonary Medicine and Critical Care, 1430 Tulane Ave., New Orleans, Louisiana 70112, USA. E-mail: lsaketk{at}tulane.edu ER -