Editorial: The Vital Role of Randomized Controlled Trials in <i>Arthritis &amp; Rheumatology</i>
Authors: Daniel H. Solomon, Michael E. Weinblatt, Richard J. Bucala
Journal: Arthritis & Rheumatology (2015)

In this issue of Arthritis & Rheumatology (A&R), Sieper and colleagues report the results of an important trial demonstrating the benefits of a tumor necrosis factor (TNF) antagonist for the treatment of nonradiographic spondyloarthritis 1. As optimal treatment for this condition evolves, well-designed randomized controlled trials (RCTs) will play a pivotal role in defining the standard of care for one of the more common inflammatory arthritides. We highlight this study not only because of its importance to rheumatology but also because of the vital role of RCTs in A&R. Throughout the 57-year history of A&R, RCTs have always played a prominent role. Major advances in our understanding of treatment, pathobiology, the mechanisms of action of a treatment, and new avenues of scientific investigation are facilitated by RCTs. Some of the major RCTs published in A&R throughout the many decades document the roles of TNF antagonists in rheumatoid arthritis 2, 3, cyclophosphamide and belimumab in systemic lupus erythematosus 4, 5, nonpharmacologic therapies in osteoarthritis 6, 7, novel therapies in gout 8, 9, and various treatments in vasculitis 10, 11 With this issue, which begins the tenure of the new editorial team, we rededicate Arthritis & Rheumatology to the goal of publishing the most important RCTs in our field. The importance of RCTs in A&R is reflected by a new section of the journal that is dedicated to RCTs, with one of us (MEW), a senior clinical trials investigator, as the section advisor. As with the RCT published in the current issue 1, A&R will now offer fast-track reviews. For example, the total review time for the article by Sieper and colleagues 1, from submission to acceptance, was 20 days. Authors of RCTs desiring a fast-track review need to contact the Editor in Chief (RJB) or Deputy Editor (DHS) at least 14 days prior to submission to facilitate such a review. The new section will focus on phase I, phase II, and phase III RCTs. A phase III RCT using approved drugs for new indications, such as that reported by Sieper and colleagues, will also be considered for this section and for fast-track review. Nonrandomized phase IV studies will be published in other sections of the journal, and phase I and phase II studies will typically not receive fast-track status, except under circumstances in which the findings are exceptionally noteworthy. In addition, A&R embraces the important role of effectiveness studies in the current research milieu. Efficacy studies (how interventions work in idealized settings, such as an RCT) and effectiveness studies (how interventions work in typical settings, such as registries and pragmatic controlled clinical trials) contribute complementary and critical information for determining best practice. RCTs with negative results also provide important information for drug developers, providers, and patients that will be embraced by this journal. An analysis of the RCT presented in the current issue highlights why such studies are important to our field 1. First, the authors defined a study question with great clinical relevance: whether anticytokine therapy would increase attainment of 20% improvement according to the criteria of the Assessment of SpondyloArthritis international Society among patients with ankylosing spondylitis who have not developed changes apparent on plain radiographs. Second, they selected a study sample reflecting typical patients with AS that was sufficiently large to obtain a clear answer. Third, the conduct of the trial involved the use of rigorous clinical trial methods, with adequate masking, successful randomization, appropriate safety monitoring, and clear prespecified analyses (https://www.clinicaltrials.gov/ct2/show/NCT01453725?term=NCT01453725&rank=1). Finally, the interpretation of the results does not reach beyond the data. The authors let the data speak. Pragmatic trials—reflecting conditions closer to typical practice than many double-blind RCTs—will take on a greater prominence 12. The design of relevant RCTs for some rheumatic diseases requires innovative approaches, using adaptive designs in which strategies (not drugs) need to be tested or in which only specific subgroups of patients are likely to respond 13. In some adaptive and nonadaptive trial designs, biomarkers will be used to identify relevant subgroups of patients who are likely or unlikely to respond to a given treatment. Arthritis & Rheumatology aspires to leadership in the delivery of high-quality and timely information that is useful to clinicians, scientists, and policy makers. This will include a broad range of clinical, basic, and population science publications dealing with common rheumatic diseases as well as those that are rare. RCTs often reflect the culmination of years of basic science studies, the translation of mechanistic studies into therapeutic options, and proof (or disproof) of clinical relevance. The ultimate goal of A&R continues to be advancement of the scientific basis of rheumatology and to improve clinical practice. We look forward to publishing more high-quality RCTs in A&R. All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published.