Determination of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire-Revised respiratory symptom scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection

Abstract

Background: The Cystic Fibrosis Questionnaire-Revised (CFQ-R) is a validated patient-reported outcome (PRO) containing both generic scales and scales specific to cystic fibrosis (CF). The minimal clinically important difference (MCID) score for a PRO corresponds to the smallest clinically relevant change a patient can detect. MCID scores for the CFQ-R respiratory symptom (CFQ-R-Respiratory) scale were determined using data from two 28 day, open-label, tobramycin inhalation solution (TIS) studies in patients with CF and chronic Pseudomonas aeruginosa airway infection. At study enrollment, patients in the study 1-exacerbation had symptoms indicative of pulmonary exacerbation (n = 84; < 14 years of age, 31 patients; > or = 14 years of age, 53 patients); patients in study 2-stable had stable respiratory symptoms (n = 140; < 14 years of age, 14 patients; > or = 14 years, 126 patients).

Methods: The anchor-based method utilized a global rating-of-change questionnaire (GRCQ) that assessed patients' perceptions of change in their respiratory symptoms after TIS treatment. The mean change from baseline CFQ-R-Respiratory scores were mapped onto the GRCQ to estimate the MCID. The two distribution-based methods were as follows: (1) 0.5 SD of mean change in CFQ-R-Respiratory scores (baseline to end of TIS treatment); and (2) 1 SEM for baseline CFQ-R-Respiratory scores. Triangulation of these three estimates defined the MCIDs.

Results: MCID scores were larger for patients in study 1-exacerbation (8.5 points) than for those in study 2-stable (4.0 points), likely reflecting differences in patient disease status (exacerbation/stable) between these studies.

Conclusions: Patient benefit from new and current CF therapies can be evaluated using changes in CFQ-R-Respiratory scores. Using the MCID provides a systematic way to interpret these changes, and facilitates the identification of CF treatments that improve both symptoms and physiologic variables, potentially leading to better treatment adherence and clinical outcomes. Trial registration (study 1-exacerbation): Australian-New Zealand Clinical Trials Registry Identifier: ACTRN 12605000602628 Trial registration (study 2-stable): ClinicalTrials.gov Identifier: NCT00104520.

Figures

Figure 1

Correlations between efficacy measures: data from individual patients. Change in CFQ-R-Respiratory scores vs the percentage change in FEV1 (in liters) after TIS treatment (day 28) is shown for study 1-exacerbation (top left, A) and study 2-stable (bottom left, C). Change in CFQ-R-Respiratory scores vs GRCQ respiratory functioning scores after TIS treatment (day 28) is shown for study 1-exacerbation (top right, B) and study 2-stable (bottom right, D). Each circle represents data from a single patient. Pearson correlation coefficients are shown. The GRCQ change categories are represented by gray and white stripes (top right, B, and bottom right, D).