Measuring Hunger Severity in Rare MC4R Pathway Diseases: Development and Psychometric Evaluation of the Most Hunger Item.
The Most Hunger item effectively measures hunger severity in patients with MC4R pathway diseases, providing valuable insights into treatment benefits.
Where it sits
this study against the rest of the setmelanotide corpusSummary and findings
This study evaluated the Most Hunger item, a patient-reported outcome measure assessing hunger in patients with MC4R pathway diseases. It involved individuals with LEPR or POMC deficiency, Bardet-Biedl syndrome, and acquired hypothalamic obesity. The study reported changes in hunger severity pre- and post-treatment with setmelanotide.
Abstract
<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.<h4>Trial registrations</h4>ClinicalTrials.gov identifiers, NCT03287960, NCT02896192, NCT03746522, and NCT05774756.
Background
This paper addresses the measurement of hunger severity in patients with rare MC4R pathway diseases, such as LEPR deficiency and POMC deficiency. Prior to this study, there was limited understanding of how these patients perceive hunger and the impact of treatments like setmelanotide. The development of a reliable patient-reported outcome measure is essential for assessing treatment benefits from the patient's perspective.
Methods
The study utilized qualitative interviews with individuals diagnosed with LEPR or POMC deficiency, BBS, and acquired hypothalamic obesity. The psychometric evaluation assessed reliability, validity, responsiveness, and meaningful within-patient change thresholds of the Most Hunger item based on responses from phase 3 trials. Participants included individuals aged ≥12 years.
Results
The primary endpoint indicated that the Most Hunger item had MWPC thresholds of 1.5-2.6 for LEPR or POMC deficiency, 0.95-1.6 for BBS, and 2.4-3.7 for acquired HO. The item demonstrated moderate to good test-retest reliability, and convergent correlations supported its validity.
Interpretation
The findings suggest that the Most Hunger item is a valid measure for assessing hunger severity in patients with MC4R pathway diseases. While the results are statistically significant, the clinical relevance of the MWPC thresholds should be interpreted cautiously. Limitations include reliance on self-reported data and the potential for bias in patient responses.
Key findings
- MWPC threshold for Most Hunger in LEPR or POMC deficiency was estimated as 1.5-2.6.
- MWPC threshold for Most Hunger in BBS was estimated as 0.95-1.6.
- MWPC threshold for Most Hunger in acquired HO was estimated as 2.4-3.7.
- The Most Hunger item had moderate to good test-retest reliability.
- Patients described an unrelenting hunger prior to treatment and an impactful reduction in hunger post treatment.
Limitations
- self-reported measures may introduce bias
- psychometric evaluation based on phase 3 trial data
- not all patient populations may be represented