Psychometric evaluation of the Activity Impairment in Migraine-Diary (AIM-D) using data from a phase 3 clinical trial (ADVANCE) in patients with episodic migraine

The psychometric properties of the Activity Impairment in Migraine‐Diary were established using phase 3 episodic migraine trial data, indicating this scale is suitable to construct clinical trial endpoints that evaluate the impact of migraine on performing daily activities and physical impairment. Background: The Activity Impairment in Migraine‐Diary (AIM‐D) is a novel patient‐reported outcome (PRO) measure consisting of 11 items and 2 domains (Performance of Daily Activities [PDA; 7 items] and Physical Impairment [PI; 4 items]) designed to evaluate the impact of migraine on activity impairment. The objective of this study was to evaluate the psychometric properties and establish meaningful within‐patient change (MWPC) threshold estimates for the AIM‐D, using phase 3 trial data. Methods: In a 12‐week, double‐blind, controlled trial (NCT03777059), participants with episodic migraine (EM) were randomized to receive atogepant 10 mg QD, 30 mg QD, 60 mg QD, or placebo. AIM‐D PDA and PI domains (each scored on a 0‐100 scale) were key secondary endpoints of this study and were completed daily using an electronic diary. The AIM‐D was collected daily with the same set of questions administered in headache (HA) and non‐headache (NHA) versions. Monthly domain scores are calculated by summing the non‐missing daily domain scores (HA and NHA days combined) and dividing the number of non‐missing daily scores with the availability of at least 14 days of non‐missing scores. Other PRO instruments completed periodically on an electronic tablet included Migraine Specific Quality of Life Questionnaire (MSQ v2.1), Patient Global Impression of Severity (PGI‐S), Patient Global Impression of Change (PGI‐C), and the 6‐item Headache Impact Test (HIT‐6). Psychometric properties were evaluated using confirmatory factor analysis (CFA), tests of reliability, validity (convergent and known‐groups), and responsiveness. MWPC threshold estimates were established using anchor‐based methods supported by distribution‐based methods, and empirical cumulative distribution function (eCDF) and probability density function (PDF) curves. Results: Of 910 participants enrolled, 719 were included in the PRO analysis (mean [range] age: 42 [18‐73] years; 88% were female). CFA supported the 2‐domain factor structure (Table). Both domains demonstrated good internal consistency (Cronbach's alpha: PDA = 0.98, PI = 0.95), and test‐retest reliability (intraclass correlation coefficients: PDA = 0.77, PI = 0.80). Construct validity was supported by moderate/strong correlations at baseline between the AIM‐D domains and migraine/headache days (0.30‐0.45) and activity level/limitation (‐0.33 to 0.92). Known‐groups validity showed the 2 domain scores significantly differentiated groups defined by monthly migraine days (p < 0.0001) and PGI‐S (p < 0.0001). Each domain score differed significantly across the anchors, PGI‐S, PGI‐C, and percent monthly migraine days. Anchor‐based results demonstrated MWPC estimates of =9 points for the PDA domain and =6 points for the PI domain. Conclusion: The psychometric properties of the AIM‐D were confirmed and MWPC estimates were established using phase 3 EM trial data. The AIM‐D is suitable to construct clinical trial endpoints to evaluate the impact of migraine on performance of daily activities and physical impairment in patients with EM.