title: Systematic literature review and validity evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in patients with multiple sclerosis.
abstract: BACKGROUND
  There are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of therapeutic interventions. We examined to what extent the psychometric properties of two accepted instruments--EDSS and MSFC--meet methodological standards and the value they have in clinical trials.
  
  
  METHODS
  We conducted a systematic literature search in relevant databases [MEDLINE (PubMed), ISI Web of Science, EMBASE, PsycINFO & PSYNDEX, CINAHL] yielding 3,860 results. Relevant full-text publications were identified using abstract and then full-text reviews, and the literature was reviewed.
  
  
  RESULTS
  For evaluation of psychometric properties (validity, reliability, sensitivity of change) of EDSS and MSFC, 120 relevant full-text publications were identified, 54 of them assessed the EDSS, 26 the MSFC and 40 included both instruments. The EDSS has some documented weaknesses in reliability and sensitivity to change. The main limitations of the MSFC are learning effects and the z-scores method used to calculate the total score. However, the methodological criterion of validity applies sufficiently for both instruments.For use in clinical studies, we found the EDSS to be preferred as a primary and secondary outcome measure in recent studies (50 EDSS, 9 MSFC).
  
  
  CONCLUSIONS
  Recognizing their strengths and weaknesses, both EDSS and MSFC are suitable to detect the effectiveness of clinical interventions and to monitor disease progression. Almost all publications identify the EDSS as the most widely used tool to measure disease outcomes in clinical trials. Despite some limitations, both instruments are accepted as endpoints and neither are discussed as surrogate parameters in identified publications. A great advantage of the EDSS is its international acceptance (e.g. by EMA) as a primary endpoint in clinical trials and its broad use in trials, enabling cross-study comparisons.
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Walther-Rathenau-Strasse 48, 17475 Greifswald, Germany. sandra.meyer-moock@uni-greifswald.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Meyer-Moock
authors.forename: You-Shan
authors.initials: YS
authors.lastname: Feng
authors.forename: Mathias
authors.initials: M
authors.lastname: Maeurer
authors.forename: Franz-Werner
authors.initials: FW
authors.lastname: Dippel
authors.forename: Thomas
authors.initials: T
authors.lastname: Kohlmann
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods; D004185:Disability Evaluation; D006801:Humans; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology*; D011594:Psychometrics / Q000379:methods / Q000592:standards*