Validation of test performance characteristics and minimal clinically important difference of the 6-minute walk test in patients with idiopathic pulmonary fibrosis

Respir Med. 2015 Jul;109(7):914-22. doi: 10.1016/j.rmed.2015.04.008. Epub 2015 Apr 24.


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.

Keywords: 6-minute walk test; Dyspnea; Idiopathic pulmonary fibrosis; Lung function; Minimal clinically important difference.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Exercise Test / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Idiopathic Pulmonary Fibrosis / diagnosis*
  • Idiopathic Pulmonary Fibrosis / drug therapy
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Male
  • Middle Aged
  • Prognosis
  • Pyridones / therapeutic use
  • Quality of Life*
  • Surveys and Questionnaires
  • Time Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Walking / physiology*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Pyridones
  • Tumor Necrosis Factor-alpha
  • pirfenidone