title: A comparison of rheumatoid arthritis and systemic lupus erythematosus trial design: a commentary on ways to improve the number of positive trials in SLE.
abstract: OBJECTIVE
  Recent systemic lupus erythematosus (SLE) randomised controlled trials (RCTs) were examined for potential design flaws and compared to rheumatoid arthritis (RA) RCT over the same time period to suggest modifications to SLE RCTs that could help improve the potential success rate of future SLE trials.
  
  
  METHODS
  RA and SLE biologics RCTs published between 2005 and July 2013 were identified using PubMed. Inclusion criteria, study design, outcome measures, sample size calculations, patient baseline characteristics steroid use in the protocol and results were extracted and compared.
  
  
  RESULTS
  All trials required active disease for enrolment. Twenty-two RA RCTs and eight SLE RCTs were included. All RA RCTs used either a partial or continuous measure of improvement. SLE RCTs used SLEDAI, BILAG, SLAM, SRI and BICLA. RA trials were larger (543 vs. 376 participants). Concomitant corticosteroid use was stable in 100% of RA trials while all SLE RCTs allowed dose tapering. RA trials were mostly in methotrexate or DMARD inadequate responders whereas SLE trials allowed for the presence or absence immunosuppressives within all trials. Sample sizes in RA were determined on a change in disease activity or proportion meeting a disease state. Positive trials were found in 100% of RA RCTs and 25% of SLE RCTs.
  
  
  CONCLUSIONS
  The potential insensitivity of SLE disease activity indices to partial improvements may result in type II errors in SLE RCTs. Varying concomitant pharmacotherapy, especially corticosteroid use, in SLE may blunt observed treatment effects. Steroid tapering should be considered a trial outcome in isolation. More realistic sample size calculations are needed in SLE.
authors: University of Toronto Medical School, Toronto, Canada.
authors: Amy
authors: A
authors: Miles
authors: Schulich School of Medicine & Dentistry, University of Western Ontario, St. Joseph's Health Care, London, Canada. janet.pope@sjhc.london.on.ca.
authors: Janet E
authors: JE
authors: Pope
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000188:drug therapy*; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012074:Remission Induction; D012107:Research Design; D018401:Sample Size; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents