Justifying score interpretation thresholds for the Asthma Control Questionnaire (ACQ-5) in a contemporary asthma...

The 5-item Asthma Control Questionnaire (ACQ-5) is widely used in clinical trials to assess the adequacy of asthma symptom control and any changes in asthma control as a result of treatment. Evidence supporting the psychometric properties of the ACQ-5, including a 0.5-threshold for meaningful improvement, was derived using methods that are no longer recommended in the literature or by regulatory authorities. The primary objective of this research was to derive meaningful change estimates using contemporary methods to evaluate clinically important change for the ACQ-5. A secondary objective was to evaluate the applicability of the existing ACQ-5 asthma control threshold for defining "well-controlled" asthma (ACQ-5 ≤ 0.75).

Measurement properties (item performance, reliability, validity, and responsiveness) were assessed prior to evaluating meaningful change, using data from a sample of 196 adults with inadequately controlled moderate-to-severe asthma from a placebo-controlled, Phase 2 study of rilzabrutinib (NCT05104892). Anchor- and distribution-based analyses were used to derive meaningful within-patient change (MWPC) and meaningful between-group difference (MBGD). Applicability of the existing ACQ-5 asthma control threshold was evaluated by plotting the positive predictive value (PPV) and negative predictive value (NPV) of the ACQ-5 total score in the current study against the PPV and NPV calculated in the original Juniper et al. (2006) study.

High internal consistency (Cronbach's alpha = 0.90), moderate-to-strong convergent validity (r range: 0.52-0.83), and ability to detect improvements in asthma control based on psychometric and physiological measures were demonstrated for the ACQ-5. Test-retest reliability results were poor-to-moderate (intraclass correlation coefficient range: 0.30-0.66). Of the anchor-based estimates derived (0.2 to 1.6), empirical cumulative distribution function plots supported 0.6 or 0.8 as appropriate MWPC thresholds. Estimated MBGD ranged from 0.2 to 0.6. PPV/NPV plots supported continued use of a 0.75- threshold to determine "well-controlled" asthma.

Contemporary score interpretation methods support a MWPC threshold of ≥ 0.6, which is functionally identical to the extant threshold of ≥ 0.5, given the 0.2 increments of the ACQ-5 scale. MBGD ranged from 0.2 to 0.6, further supporting use of the established ≥ 0.5 threshold to define clinically important change between groups of patients. A "well-controlled" threshold of ≤ 0.75 was also supported.