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.
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.
Quittner
Alexandra L
AL
University of Miami, Coral Gables, FL. Electronic address: aquittner@miami.edu.
Modi
Avani C
AC
Cincinnati Children's Hospital Medical Center and the University of Cincinnati, Cincinnati, OH.
Wainwright
Claire
C
Royal Children's Hospital and University of Queensland, Brisbane, QLD, Australia.
Otto
Kelly
K
Kelly Otto Consulting, Seattle, WA.
Kirihara
Jean
J
JKirihara Consulting Services, Seattle, WA.
Montgomery
A Bruce
AB
Gilead Sciences Inc, Seattle, WA.
D000280:Administration, Inhalation; D000293:Adolescent; D000367:Age Factors; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002648:Child; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D018410:Pneumonia, Bacterial / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology; D011552:Pseudomonas Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D011788:Quality of Life; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
D000900:Anti-Bacterial Agents