Reliability and Minimal Clinically Important Differences of FVC Results from the Scleroderma Lung Studies (SLS-I and SLS-II)

Rationale: FVC percent predicted (FVC%) is the primary outcome measure in clinical trials of systemic sclerosis interstitial lung disease. For interpretation of change in the FVC% over time, it is important to define whether these changes are clinically meaningful. Objectives:: To assess the reliability and the minimal clinically important differences (MCID) for FVC% in the Scleroderma Lung Study I and II (SLS-I and -II). Methods: Using data from SLS-I and -II (N = 300), we evaluated the test-retest reliability for FVC% (screening vs. baseline) using intraclass correlation. MCID estimates at 12 months were calculated in the pooled cohort (SLS-I and -II) using two anchors: Transition Dyspnea Index (>= change of 1.5 units for improvement and worsening, respectively) and the Medical Outcomes Short Form-36 Health Transition question ("Compared with one year ago, how would you rate your health in general now"?), where "somewhat better" or "somewhat worse" were defined as the MCID estimates. We next assessed the association of MCID estimates for improvement and worsening of FVC% with patient-reported outcomes (PROs) and computer-assisted quantitation of extent of fibrosis (QLF) and of total interstitial lung disease (QILD) on high-resolution computed tomography. Student's t test was used to compare the mean difference in outcomes between the MCID improvement/worsening and the "no change" group. Measurements and Main Results: Reliability of FVC%, assessed at a mean of 34 days, intraclass correlation was 0.93 for the pooled cohort. The MCID estimates for the pooled cohort at 12 months for FVC% improvement ranged from 3.0% to 5.3% and for worsening from 23.0% to23.3%. FVC% improvement by greater than or equal to MCID was associated with either statistically significant or numerical improvements in some PROs, QILD, and QLF, whereas FVC% worsening greater than or equal to MCID was associated with statistically significant or numerical worsening of PROs, QILD, and QLF. Conclusions: FVC% has acceptable test-retest reliability, and we have provided the MCID estimates for FVC% in systemic sclerosis interstitial lung disease-based changes at 12 months from baseline in two clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT00004563 for SLS-I and NCT00883129 for SLS-II).