title: Outcome measurements in scleroderma: results from a delphi exercise.
abstract: OBJECTIVE
  To obtain a consensus on the minimal clinically relevant treatment effect in various scleroderma disease outcome measures to be used in future clinical trials.
  
  
  METHODS
  A Delphi consensus building exercise using a survey was sent out to members of the Scleroderma Clinical Trials Consortium (SCTC). The 65 SCTC members were divided into 2 groups. Group 1 was informed, in a cover letter, of the usual American College of Rheumatology 20% response results in randomized trials using effective biologic treatments for rheumatoid arthritis, while Group 2 was not. The first round of the exercise presented the scleroderma experts with a survey composed of 95 questions/clinical scenarios divided into 8 categories. These included situations where the treatment group improved, or worsened, or where some outcome measures improved, while others worsened. From the responses of this first round, a mean, mode, median, and range of responses for each of the 95 questions was obtained. This information was sent out, in the second round of the Delphi exercise, only to those respondents who answered the first round. The respondent's previous answer and the mean and range from the first round were provided for each question. It gave respondents the option to change any of their initial responses. The median of their responses in the second round was used to calculate the values for the minimal clinically relevant treatment effect.
  
  
  RESULTS
  Thirty-two of the 65 SCTC members returned the first round of the Delphi exercise. Twenty-eight members returned the second round. Intraclass correlation coefficients between responses to round 1 and 2 were calculated for the questions. These varied from 0.99 (excellent agreement) to 0.02 (poor agreement). The p value was under 0.09 for 9 questions and under 0.19 for 20 questions. Standard deviations (SD) were calculated and were found to be lesser for each of the questions in round 2 when compared to the SD in responses from round 1, thus indicating a movement towards a consensus by the second round. An average of 33% of the responses were changed by the respondents in the second round of the Delphi exercise to a value closer to the median/average of the first round's responses. A range in required values for the minimal clinically relevant treatment effect for Modified Rodnan skin score is 3 to 7.5 units, Health Assessment Questionnaire Disability Index (HAQ-DI) 0.2 to 0.25 units, HAQ pain 0.2 to 0.3 units, MD global (100 mm visual analog scale) 8 to 13, patient global assessment 10 to 12, and diffusing capacity (percentage predicted) 9 to 10. The scenarios were especially weighted towards overall disease modification, thus organ-specific measures, such as 6 minute walk time (which has been used in many pulmonary artery hypertension trials), forced vital capacity, and a dyspnea rating (which may be important in scleroderma lung trials), were not included in the survey.
  
  
  CONCLUSIONS
  Our study begins to address the current deficiency in our knowledge of appropriate values for the minimal clinically relevant treatment effect in various scleroderma disease outcome measures. A consensus could be achieved, or at least a range of minimal clinically relevant treatment effect values could be found for several outcome measurements. Of course, this consensus statement will be modified by evidence as it accrues in each consensus area.
authors.affiliation: Division of Rheumatology, Department of Medicine, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Hashim
authors.initials: H
authors.lastname: Gazi
authors.forename: Janet E
authors.initials: JE
authors.lastname: Pope
authors.forename: Philip
authors.initials: P
authors.lastname: Clements
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Medsger
authors.forename: Richard W
authors.initials: RW
authors.lastname: Martin
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.forename: Bashar
authors.initials: B
authors.lastname: Kahaleh
authors.forename: Frank A
authors.initials: FA
authors.lastname: Wollheim
authors.forename: Murray
authors.initials: M
authors.lastname: Baron
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Csuka
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Jill F
authors.initials: JF
authors.lastname: Belch
authors.forename: Samina
authors.initials: S
authors.lastname: Hayat
authors.forename: Edward V
authors.initials: EV
authors.lastname: Lally
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Korn
authors.forename: Laszlo
authors.initials: L
authors.lastname: Czirjak
authors.forename: Ariane
authors.initials: A
authors.lastname: Herrick
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Voskuyl
authors.forename: Pius
authors.initials: P
authors.lastname: Bruehlmann
authors.forename: Murat
authors.initials: M
authors.lastname: Inanc
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.forename: Carol
authors.initials: C
authors.lastname: Black
authors.forename: Michael H
authors.initials: MH
authors.lastname: Ellman
authors.forename: Larry W
authors.initials: LW
authors.lastname: Moreland
authors.forename: Naomi F
authors.initials: NF
authors.lastname: Rothfield
authors.forename: Vivien
authors.initials: V
authors.lastname: Hsu
authors.forename: Maureen
authors.initials: M
authors.lastname: Mayes
authors.forename: Kevin M
authors.initials: KM
authors.lastname: McKown
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.forename: James R
authors.initials: JR
authors.lastname: Siebold
mesh_terms: D002986:Clinical Trials as Topic; D003697:Delphi Technique; D006233:Persons with Disabilities; D023381:Endpoint Determination; D006304:Health Status; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000592:standards*; D012219:Rheumatology / Q000592:standards; D012595:Scleroderma, Systemic / Q000628:therapy*; D016896:Treatment Outcome