Abstract
OBJECTIVE: The objective of the analyses described here was to develop thresholds defining clinically meaningful response on the total and item scores of the 6-item short-form Headache Impact Test (HIT-6) in a population of patients with chronic migraine (CM). BACKGROUND: The HIT-6 is a short, easily understood, and useful measure of the impact of headache on daily life. Though widely used, limited literature supports a threshold value for clinically meaningful response within individuals over time for the HIT-6 total score and for the item scores, especially in the CM population. METHODS: PROMISE-2 is a randomized, double-blind, multicenter study comparing intravenous eptinezumab 100 and 300 mg with placebo for the preventive treatment of CM. Responder definitions for HIT-6 total and items scores using data from PROMISE-2 study were calculated via distribution-based and anchor-based methods. Distribution-based methods included half of the baseline standard deviation and baseline standard error of measurement. The change from baseline to week 12 in HIT-6 scores was assessed using the following anchors: patient global impression of change, reduction in migraine frequency, and change in EuroQol 5 dimensions 5 levels visual analog scale. Values from the literature and PROMISE-2 analyses were plotted against the cumulative distribution function of change values (baseline to week 12) and used to triangulate to empirically support clinically meaningful change definitions for the HIT-6 total and item scores in patients with CM. RESULTS: From the literature, 5 articles provided 7 candidate values for a responder threshold for the HIT-6 total score. From distribution- and anchor-based methods, 5 candidate values were derived from PROMISE-2 data. Using the median of all candidate values, a HIT-6 total score responder definition estimate of -6 (ie, ≥6-point improvement in the total score) appears most appropriate for discriminating between individuals with CM who have experienced meaningful change over time and those who have not. For item-level analyses using anchor-based methods, the responder definition for items 1-3 ("severe pain," "limits daily activities," and "lie down") was a 1-category improvement in response (eg, from Sometimes to Rarely); for items 4-6 ("too tired," "felt fed up or irritated," and "limits concentration"), a 2-category improvement in response (eg, from Always to Sometimes) was clinically meaningful. CONCLUSIONS: Using a multifaceted, statistically-based approach, the recommended responder definition for the HIT-6 total score in the CM population is a ≥6-point decrease, consistent with previous literature. Anchor-based item-level responder thresholds were defined as a decrease of 1 or 2 categories, depending on the item. These CM-specific values will provide researchers and clinicians a means to interpret clinically meaningful change in the HIT-6 total and item scores and may facilitate the measurement of treatment benefits in specific functional domains of the HIT-6.