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Design, Quality, and Bias in Randomized Controlled Trials of Systemic Lupus Erythematosus
FOTINI B. KARASSA, ATHINA TATSIONI, and JOHN P.A. IOANNIDIS
ABSTRACT.
Methods. RCT with at least 5 patients with SLE were retrieved from MEDLINE, EMBASE, and the Cochrane Library. We analyzed study design, quality of reporting, and trial results. Results. Ninety-four trial reports (37 on lupus nephritis) were eligible with 2,257 SLE patients (n = 795 in lupus nephritis trials). Median sample size was 28 patients. Fifty-one trials (54.3%) were double blind, but only 31 (33.0%) mentioned the randomization mode, only 19 (20.2%) described allocation concealment, and only 7 (7.5%) were adequately powered. Sixty-three trials (67%) described adequately reasons for withdrawals. Nephritis trials had on average longer followup (p = 0.001) and were less likely to be double blind (p < 0.001), to describe reasons for withdrawals [both overall (p = 0.008) and per arm (p = 0.009)] and to involve a comparison against placebo or no treatment (p < 0.001). Larger trials scored higher on several quality characteristics. Significant efficacy or trend for efficacy was claimed in 72 reports (76.6%) and this was even more common in trials published in 1999-2002 (89.5%). Significant efficacy was found more frequently in trials that clearly specified withdrawals per arm (p = 0.001) and outcomes (p = 0.001) and used intention-to-treat analyses (p = 0.03). Besides outcome specification, no other quality variables seemed to improve significantly over time. Conclusion. Several aspects of the design and reporting of RCT on SLE can be improved. Larger, adequately powered, and accurately reported trials are needed. (J Rheumatol 2003;30:979-84) Key Indexing Terms:
SYSTEMIC LUPUS ERYTHEMATOSUS
From the Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, the University of Ioannina School of Medicine, Ioannina, Greece and the Division of Clinical Care Research, Tufts-New England Medical Center, Boston, Massachusetts, USA. F.B. Karassa, MD; A. Tatsioni, MD, Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine; J.P.A. Ioannidis, MD, Clinical Trials and Evidence-Based Medicine Unit, Chair, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine and the Division of Clinical Care Research, Tufts-New England Medical Center. Address reprint requests to Dr. J.P.A. Ioannidis, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, 45110, Greece. E-mail: jioannid@cc.uoi.gr Submitted July 15, 2002; revision accepted October 31, 2002. |