Background <p>The Asthma Daytime and Nighttime Symptom Diaries (ADSD and ANSD) were developed to provide an accurate and standardized instrument for assessing patient-reported severity of asthma symptoms. While previous evidence supports the content validity and cross-sectional measurement properties of the ADSD and ANSD, the US Food and Drug Administration (FDA) qualification statement for these tools recommended further evaluation of their longitudinal measurement properties and the interpretation of within-patient meaningful change (WPMC). Therefore, two complementary studies were designed to assess cross-sectional and longitudinal measurement properties and estimate thresholds for WPMC for the ADSD/ANSD in patients with moderate-to-severe asthma, responding to measurement gaps identified in the FDA statement.</p> Methodology <p>Quantitative evaluation of ADSD/ANSD (score range 0 to 10) measurement properties was performed in a real-world observational study (RWS; ≥16 years old; moderate-to-severe asthma) and a randomized controlled trial (RCT; ≥12 years old; severe asthma with type 2 inflammation). Cross-sectional and longitudinal measurement properties were assessed and WPMC thresholds estimated.</p> Results <p>A total of 576 patients with moderate-to-severe asthma were recruited across both studies. The RWS (<i>n</i> = 241) and RCT (<i>n</i> = 335) both found the ADSD/ANSD to have high internal consistency and test-retest reliability with Cronbach’s α-coefficients ≥0.94 and intraclass correlation coefficients ≥0.90. Evidence in support of the unidimensional scoring solution for both the ADSD and ANSD was established via confirmatory factor analysis across timepoints and studies, and evidence of construct validity was demonstrated via convergent and known-groups validity testing. In the blinded RCT analysis, the threshold for WPMC was estimated at 1.2 for the ADSD and 1.5 for the ANSD. In the RWS, the WPMC threshold for within-patient improvement was estimated to be from 0.6 to 1.3 for ADSD and from 0.8 to 1.4 for ANSD across 6- and 10-week intervals. </p> Conclusions <p>This study directly addresses the evidence gaps identified by the FDA, demonstrating that the ADSD and ANSD are reliable and valid tools for the measurement of daily symptoms in patients with moderate-to-severe asthma, and are capable of detecting WPMC. Values derived from the RCT analysis support a recommendation for thresholds for meaningful within-patient change of 1.2 and 1.5 for the ADSD and ANSD, respectively.</p> Clinical trial registration <p>GSK ID: 217640; NCT04719832.</p>