What are minimal important changes for asthma measures in a clinical trial?

Abstract

In this study, the perceptions of asthmatics to change in their disease was associated with observed changes in clinical asthma measures, in order to identify the threshold where changes in clinical asthma measures are perceivable by patients.The study included 281 asthmatic patients, aged 18±63 yrs, in a randomized, placebo-controlled clinical trial of a leukotriene antagonist. Changes were related in: 1) asthma symptom scores; 2) inhaled b-agonist use; 3) forced expiratory volume in one second (FEV1); and 4) peak expiratory flow (PEF) to a global question that queried overall change in asthma since starting the study drug. Additional analyses examined differences in the group reporting minimal improvement by treatment (active treatment versus placebo), sex and age groups.The average minimal patient perceivable improvement for each measure was: 1) -0.31 points for the symptom score on a scale of 0±6; 2) -0.81 puffs . day -1 for inhaled bagonist use; 3) 0.23 L for FEV1; and 4) 18.79 L . min -1 for PEF. In general placebotreated patients and older patients, who reported minimal improvement, experienced less mean improvement from baseline than active-treated patients and younger patients, who reported minimal improvement.Determining the minimal patient perceivable improvement value for a measure may be helpful to interpret changes. However, interpretation should be carried out cautiously when reporting a single value as a clinically important change. Eur Respir J 1999; 14: 23±27. Asthma is a chronic respiratory disease characterized histologically by airway inflammation and mucus hypersecretion, and clinically by reversible airway obstruction and specific patient-reported symptoms [1]. In clinical trials, changes in asthma are measured by pulmonary function tests, such as forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF), as well as by b-agonist inhaler use, and validated symptom scales that capture patient-reported symptoms [2]. While a clinical trial can be powered to find small differences between treatment groups on any one of these asthma measures, the meaning of these changes is often unknown. The question is often asked: "Do differences in asthma measures noted at the end of the study matter to the patients, that is are they clinically meaningful?". As an example, is an average of 1 or 2 puffs . day -1 decrease in b-agonist inhaler use or an increase of 8 or 10% in FEV1 perceived by patients?One method of providing clinical meaning is to relate change in one measure to a global measure of patientrated change. For example, JAESCHKE et al.[3] related average changes in scores on a health-related quality-oflife (HRQoL) questionnaire to patients' global ratings of change in their disease within an observational study environment. In this way, they provided meaning to changes in scores from baseline within groups on a newly developed HRQoL questionnaire.In this study, the theoretical framework of JAESCHKE et al. [3] was utilized in order to provide clinical meaning to changes...

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