title: The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis.
abstract: OBJECTIVE
  Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs).
  
  
  METHODS
  We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc. Forty scleroderma experts rated 20 patient profiles each and assessed whether each patient had improved or not improved over a period of 1 year. Using the profiles for which raters had reached a consensus on whether the patients were improved versus not improved (79% of the profiles examined), we fit logistic regression models in which the binary outcome referred to whether the patient was improved or not, and the changes in the core set items from baseline to followup were entered as covariates. We tested the final index in a previously completed RCT.
  
  
  RESULTS
  Sixteen of 31 core items were included in the patient profiles after a consensus meeting and review of test characteristics of patient-level data. In the logistic regression model in which the included core set items were change over 1 year in the modified Rodnan skin thickness score, the forced vital capacity, the patient and physician global assessments, and the Health Assessment Questionnaire disability index, sensitivity was 0.982 (95% confidence interval 0.982-0.983) and specificity was 0.931 (95% confidence interval 0.930-0.932), and the model with these 5 items had the highest face validity. Subjects with a significant worsening of renal or cardiopulmonary involvement were classified as not improved, regardless of improvements in other core items. With use of the index, the effect of methotrexate could be differentiated from the effect of placebo in a 1-year RCT (P = 0.02).
  
  
  CONCLUSIONS
  We have developed a CRISS that is appropriate for use as an outcome assessment in RCTs of early dcSSc.
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Veronica J
authors.initials: VJ
authors.lastname: Berrocal
authors.affiliation: Cincinnati Children's Hospital, Cincinnati, Ohio.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Giannini
authors.affiliation: Scleroderma Research Consultants, Litchfield, Connecticut.
authors.forename: James R
authors.initials: JR
authors.lastname: Seibold
authors.affiliation: University of Pennsylvania, Philadelphia.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.affiliation: University of Texas Health Science Center at Houston.
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Mayes
authors.affiliation: Jewish General Hospital and McGill University, Montreal, Quebec, Canada.
authors.forename: Murray
authors.initials: M
authors.lastname: Baron
authors.affiliation: University of California, Los Angeles.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Clements
authors.affiliation: Georgetown University, Washington, DC.
authors.forename: Virginia
authors.initials: V
authors.lastname: Steen
authors.affiliation: University of Texas Health Science Center at Houston.
authors.forename: Shervin
authors.initials: S
authors.lastname: Assassi
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Elena
authors.initials: E
authors.lastname: Schiopu
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Kristine
authors.initials: K
authors.lastname: Phillips
authors.affiliation: Boston University, Boston, Massachusetts.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Simms
authors.affiliation: Paris Descartes University and Cochin Hospital, AP-HP, Paris, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
authors.affiliation: Royal Free and University College London Medical School, London, UK.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Denton
authors.affiliation: Toronto Western Hospital and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
authors.affiliation: Toronto Western Hospital and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sindhu R
authors.initials: SR
authors.lastname: Johnson
authors.affiliation: Azienda Ospedaliero-Universitaria Careggi (AOUC) and University of Florence, Florence, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.affiliation: Schulich School of Medicine, Western University, London Campus, and St. Joseph's Health Care, London, Ontario, Canada.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Pope
authors.affiliation: Royal Adelaide Hospital and University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Proudman
authors.affiliation: Genentech/Roche, San Francisco, California.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Siegel
authors.affiliation: University of California, Los Angeles.
authors.forename: Weng Kee
authors.initials: WK
authors.lastname: Wong
authors.affiliation: Royal Brompton Hospital, London, UK.
authors.forename: Athol U
authors.initials: AU
authors.lastname: Wells
authors.affiliation: University of California, Los Angeles.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011594:Psychometrics; D016032:Randomized Controlled Trials as Topic; D012219:Rheumatology / Q000379:methods*; D045743:Scleroderma, Diffuse; D012720:Severity of Illness Index