title: Comparison of alternative primary outcome measures for use in lupus nephritis clinical trials.
abstract: OBJECTIVE
  Clinical trials of therapies for lupus nephritis have used many different primary outcome measures, ranging from complete response to time to end-stage renal disease. The objective of this study was to compare several possible outcome measures, using data from a large, multicenter trial of abatacept in lupus nephritis, to gain insight into which outcome measure, if any, was best able to discern differences among treatment groups.
  
  
  METHODS
  Study patients received either abatacept or placebo, on a background of mycophenolate mofetil and glucocorticoids. Using data from this trial, the following primary outcome measures at 24 and 52 weeks were compared: complete response rate, major clinical response rate, total response rate (complete plus partial response), improvement in proteinuria, improvement in estimated glomerular filtration rate, and frequency of treatment failure. Time to complete response was also evaluated.
  
  
  RESULTS
  Complete response rate, major clinical response rate, and time to complete response were the measures that best discriminated between the abatacept groups and placebo, and the sensitivities of these 3 measures were comparable. For these measures, sample sizes of 50 patients would have been sufficient to demonstrate a statistically significant difference between treatment and control at 52 weeks. Each of the other measures also discriminated between treatment and control, but much larger group sizes would have been required to determine statistical significance.
  
  
  CONCLUSIONS
  The choice of primary outcome measure can substantially influence the ability to detect therapeutic benefit in lupus nephritis trials. This study suggests that complete response rate, major clinical response rate at 52 weeks, and time to complete response may be the most sensitive outcome measures for detecting differences among therapeutic regimens.
authors.affiliation: Arthritis/ Immunology Unit (111R), San Francisco VA Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA. wofsyd@medsch.ucsf.edu
authors.forename: David
authors.initials: D
authors.lastname: Wofsy
authors.forename: Jan L
authors.initials: JL
authors.lastname: Hillson
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
mesh_terms: D000069594:Abatacept; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care; D011507:Proteinuria / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept; D009173:Mycophenolic Acid