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

摘要

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; ≥ 14 years of age, 53 patients); patients in study 2-stable had stable respiratory symptoms (n = 140; < 14 years of age, 14 patients; ≥ 14 years, 126 patients). nnMethods: 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. nnResults: 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. nnConclusions: 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. nnTrial registration (study 1-exacerbation): Australian-New Zealand Clinical Trials Registry Identifier: ACTRN 12605000602628 nnTrial registration (study 2-stable): ClinicalTrials.gov Identifier: NCT00104520 nnThere is growing recognition that patient-reported outcomes (PROs), such as health-related quality of life (HRQOL), are important indicators of patient benefit in clinical trials.1–3 This is particularly true for patients with chronic illnesses such as cystic fibrosis (CF), for whom disease management is both challenging and lifelong. nnPROs assess clinical benefit from the patient's perspective and must meet basic psychometric criteria, such as reliability and validity. It is also important to establish their responsiveness, or ability to detect clinical change, and to determine how to interpret the magnitude of change observed.4 The minimal clinically important difference (MCID [also abbreviated as MID in other publications]) score corresponds to the smallest clinically relevant change a patient can detect.5,6 Methods to establish MCID scores fall into the following two broad categories: anchor-based and distribution-based. Anchor-based methods rely on a series of ratings made by patients; these ratings quantify the extent of change perceived during or after a clinical intervention. This value is then mapped onto the change reported for the PRO. Essentially, anchor-based methods calibrate how much change on the PRO is perceived by patients as minimal, moderate, or large. In contrast, distribution-based methods rely on statistical tests; 0.5 SD of the change in HRQOL scores and 1 SEM are two of the statistical tests used to estimate MCIDs.7,8nnThe Cystic Fibrosis Questionnaire-Revised (CFQ-R) is a validated HRQOL measure for CF that meets US Food and Drug Administration psychometric requirements for PROs.9–12 It contains both generic and CF-specific scales and has demonstrated responsiveness in previous clinical studies.13,14 For patients with CF who have moderate-to-severe lung disease and persistent Pseudomonas aeruginosa (PA) airway infection, long-term use of tobramycin inhalation solution (TIS) is the currently recognized standard of care.15–17 We determined MCID scores for the CFQ-R respiratory symptom (CFQ-R-Respiratory) scale, applying both anchor-based and distribution-based methods, using data from two TIS clinical studies. Patients in both studies had CF and chronic PA airway infection. In the first study (study 1-exacerbation),18 patients received 28 days of therapy with open-label TIS to treat symptoms indicative of pulmonary exacerbation. In the second study (study 2-stable),19 patients with stable respiratory symptoms received 28 days of therapy with open-label TIS. The responsiveness of the CFQ-R-Respiratory scale was assessed in these patient populations by comparing changes in CFQ-R-Respiratory scores with changes in pulmonary function. This work was previously published in abstract form.20,21