Original articleDetermining a minimal important change in a disease-specific quality of life questionnaire
Abstract
This study was carried out to determine whether the minimal important difference, in evaluative quality of life instruments which use a 7-point scale, is similar across individual domains and for both improvement and deterioration. Thirty nine adults with asthma were studied, using an 8 week cohort with assessments at 0, 4 and 8 weeks. The outcomes were the Asthma Quality of Life Questionnaire and global rating of change. For overall asthma-specific quality of life and for all individual domains (activities, emotions, symptoms), the minimal important difference of quality of life score per item was very close to 0.5 (range: 0.42–0.58); differences of approximately 1.0 represented a moderate change (range: 0.77–1.51); differences greater than 1.5 represented large changes. Changes for improvement and deterioration were very similar. The changes in quality of life score that represent a minimal important difference are very similar to those observed for other evaluative instruments. The observation that the minimal important difference is consistent across domains and for both improvement and deterioration will facilitate interpretation of results of studies examining quality of life.
References (12)
- R. Jaeschke et al.
Measurements of health status: ascertaining the minimal clinically important difference
Controlled CGn Trials
(1989) - B. Kirshner et al.
A methodologic framework for assessing health indices
J Chron Dis
(1985) - J.-L. Malo et al.
A quality of life questionnaire for asthma: clinical validation of discriminative properties
J Allergy CGn Inununol
(1993) - G.H. Guyatt et al.
- G.H. Guyatt et al.
A measure of quality of life for clinical trials in chronic lung disease
Thorax
(1987) - G.H. Guyatt et al.
Development and testing of a new measure of health status for clinical trials in heart failure
J Gen Intern Med
(1989)
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Dr Guyatt is a Career Scientist of the Ontario Ministry of Health.