Abstract
Introduction
Leptin receptor (LEPR) deficiency, pro-opiomelanocortin (POMC) deficiency, Bardet-Biedl syndrome (BBS), and acquired hypothalamic obesity (HO) are diseases of the melanocortin 4 receptor (MC4R) pathway that often lead to insatiable hunger and severe obesity. As targeted treatments, such as setmelanotide, emerge for these diseases, it is critical to understand treatment benefit from patients' perspectives. This study describes the development and psychometric evaluation of the Most Hunger item, a patient-reported outcome (PRO) measure assessing hunger in patients with MC4R pathway diseases.Methods
The content validity and appropriateness of the Most Hunger item were evaluated across three separate qualitative interview studies with individuals with LEPR or POMC deficiency, BBS, and acquired HO. Semistructured interviews were conducted. The psychometric evaluation assessed the reliability, validity, responsiveness, and meaningful within-patient change (MWPC) thresholds of the Most Hunger item using responses collected during phase 3 trials of setmelanotide from participants aged ≥12 years with LEPR or POMC deficiency, BBS, or acquired HO.Results
Qualitative interview participants understood the Most Hunger item and could rate their hunger using the item. Hunger scores and patient experiences with hunger were consistent across the three patient populations; patients described an unrelenting hunger prior to treatment and an impactful reduction in hunger post treatment. The Most Hunger item had moderate to good test-retest reliability, and convergent correlations supported its validity. Among patients with LEPR or POMC deficiency, BBS, or acquired HO, MWPC thresholds for Most Hunger (0-10 response scale) were estimated as 1.5-2.6, 0.95-1.6, and 2.4-3.7, respectively.Conclusion
Individuals with these distinct MC4R pathway diseases experience similar and high levels of hunger severity, with behaviors consistent with hyperphagia. The Most Hunger item is a fit-for-purpose PRO measure of hunger to assess treatment benefit in patients aged ≥12 years with LEPR or POMC deficiency, BBS, or acquired HO.Trial registrations
ClinicalTrials.gov identifiers, NCT03287960, NCT02896192, NCT03746522, and NCT05774756.