title: Validation of test performance characteristics and minimal clinically important difference of the 6-minute walk test in patients with idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  The 6-minute walk test distance (6MWD) has been shown to be a valid and responsive outcome measure in patients with idiopathic pulmonary fibrosis (IPF). The analyses were based, however, on a single phase 3 trial and require validation in an independent cohort.
  
  
  OBJECTIVE
  To confirm the performance characteristics and estimates of minimal clinically important difference (MCID) of 6MWD in an independent cohort of patients with IPF.
  
  
  METHODS
  Patients randomized to placebo in the phase 3 CAPACITY trials who had a baseline 6MWD measurement were included in these analyses. The 6MWD and other functional parameters (lung function, dyspnea, and health-related quality of life) were measured at baseline and 24-week intervals. Validity and responsiveness were examined using Spearman correlation coefficients. The MCID was estimated using distribution- and anchor-based methods.
  
  
  RESULTS
  The analysis comprised 338 patients. Baseline 6MWD was significantly correlated with lung function measures, patient-reported outcomes, and quality-of-life measures (validity). Compared with baseline 6MWD, change in 6MWD (responsiveness) showed stronger correlations with change in lung function parameters and quality-of-life measures. Dyspnea measured by the University of California San Diego Shortness of Breath Questionnaire showed the strongest correlations with 6MWD (baseline: coefficient -0.35; 48-week change: coefficient -0.37; both p < 0.001). The distribution-based analyses of MCID using standard error of measurement yielded an MCID of 37 m, and distribution-based analyses by effect size resulted in 29.2 m. The MCID by anchor-based analysis using criterion referencing (health events of hospitalization or death) was 21.7 m.
  
  
  CONCLUSIONS
  The 6MWD is a valid and responsive clinical endpoint, which provides objective and clinically meaningful information regarding functional status and near-term prognosis. These results confirm previous findings in an independent cohort of patients with IPF.
authors.affiliation: Inova Fairfax Hospital, 3300 Gallows Rd., Falls Church, VA 22042, USA. Electronic address: steven.nathan@inova.org.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Nathan
authors.affiliation: Imperial College, South Kensington Campus, London SW7 2AZ, UK. Electronic address: ron@du-bois.co.uk.
authors.forename: Roland M
authors.initials: RM
authors.lastname: du Bois
authors.affiliation: University of Turin, San Luigi Gonzaga Medical School, Regione Gonzole, 1010043 Orbassano, Turin, Italy. Electronic address: carlo.albera@yahoo.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Albera
authors.affiliation: InterMune, Inc., 3280 Bayshore Blvd., Brisbane, CA 94005, USA. Electronic address: bbradford@intermune.com.
authors.forename: Williamson Z
authors.initials: WZ
authors.lastname: Bradford
authors.affiliation: Ruhrlandklinik, University Hospital, University of Duisburg-Essen, 45117 Essen, Germany. Electronic address: ulrich.costabel@ruhrlandklinik.uk-essen.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
authors.affiliation: Policy Analysis Inc. (PAI), 4 Davis Ct., Brookline, MA 02445, USA. Electronic address: akartashov@pai2.com.
authors.forename: Alex
authors.initials: A
authors.lastname: Kartashov
authors.affiliation: Duke University School of Medicine, 106 Research Dr., Durham, NC 27710, USA. Electronic address: paul.noble@cshs.org.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Noble
authors.affiliation: Medical University of South Carolina, 96 Jonathan Lucas St., Charleston, SC 29425, USA. Electronic address: sahnsa@musc.edu.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Sahn
authors.affiliation: Assistance Publique-Hôpitaux de Paris, 3, Ave. Victoria, 75004 Paris, France. Electronic address: dominique.valeyre@avc.aphp.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.affiliation: Policy Analysis Inc. (PAI), 4 Davis Ct., Brookline, MA 02445, USA. Electronic address: dweycker@pai2.com.
authors.forename: Derek
authors.initials: D
authors.lastname: Weycker
authors.affiliation: University of California, San Francisco, 505 Parnassus Ave., Box 0120, San Francisco, CA 94143, USA. Electronic address: tking@medicine.ucsf.edu.
authors.forename: Talmadge E
authors.initials: TE
authors.lastname: King
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D005080:Exercise Test / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011728:Pyridones / Q000627:therapeutic use; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D016138:Walking / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; D014409:Tumor Necrosis Factor-alpha; C093844:pirfenidone
keywords: 6-minute walk test; Dyspnea; Idiopathic pulmonary fibrosis; Lung function; Minimal clinically important difference