Steven D Nathan1, Roland M du Bois2, Carlo Albera3, Williamson Z Bradford4, Ulrich Costabel5, Alex Kartashov6, Paul W Noble7, Steven A Sahn8, Dominique Valeyre9, Derek Weycker10, Talmadge E King11. 1. Inova Fairfax Hospital, 3300 Gallows Rd., Falls Church, VA 22042, USA. Electronic address: steven.nathan@inova.org. 2. Imperial College, South Kensington Campus, London SW7 2AZ, UK. Electronic address: ron@du-bois.co.uk. 3. University of Turin, San Luigi Gonzaga Medical School, Regione Gonzole, 1010043 Orbassano, Turin, Italy. Electronic address: carlo.albera@yahoo.it. 4. InterMune, Inc., 3280 Bayshore Blvd., Brisbane, CA 94005, USA. Electronic address: bbradford@intermune.com. 5. Ruhrlandklinik, University Hospital, University of Duisburg-Essen, 45117 Essen, Germany. Electronic address: ulrich.costabel@ruhrlandklinik.uk-essen.de. 6. Policy Analysis Inc. (PAI), 4 Davis Ct., Brookline, MA 02445, USA. Electronic address: akartashov@pai2.com. 7. Duke University School of Medicine, 106 Research Dr., Durham, NC 27710, USA. Electronic address: paul.noble@cshs.org. 8. Medical University of South Carolina, 96 Jonathan Lucas St., Charleston, SC 29425, USA. Electronic address: sahnsa@musc.edu. 9. Assistance Publique-Hôpitaux de Paris, 3, Ave. Victoria, 75004 Paris, France. Electronic address: dominique.valeyre@avc.aphp.fr. 10. Policy Analysis Inc. (PAI), 4 Davis Ct., Brookline, MA 02445, USA. Electronic address: dweycker@pai2.com. 11. University of California, San Francisco, 505 Parnassus Ave., Box 0120, San Francisco, CA 94143, USA. Electronic address: tking@medicine.ucsf.edu.
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.
RCT Entities:
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: Isabelle Delanote; Wim A Wuyts; Jonas Yserbyt; Eric K Verbeken; Geert M Verleden; Robin Vos Journal: BMC Pulm Med Date: 2016-11-18 Impact factor: 3.317