Abstract

Background There is no consistent approach in assessing swallowing function both in clinical or research settings. However, its significance in ensuring proper nutrition, growth/ development, and overall quality of life is undeniable. We aim to introduce a novel methodology that enhances swallowing function as an outcome measure in clinical and rare disease research and demonstrate its efficacy in Niemann-Pick Type C1 (NPC1). Methods We reviewed commonly implemented qualitative and quantitative swallowing assessments in current clinical practice, including patient/proxy/clinician reports, clinical swallowing evaluation, videofluoroscopic swallow assessment (VFSS), and post-VFSS interpretive measures [American Speech Hearing Association National Outcomes Measures Scale (ASHA-NOMS) and National Institutes of Health penetration and aspiration scale (NIH-PAS)]. Data analysis involved descriptive statistics, longitudinal statistical modeling to account for NPC1-specific covariates, and Kappa weighting correlations to determine inter-rater reliability. Results Our NPC1 cohort ( n = 120) underwent baseline and longitudinal evaluations, ( n = 269 VFSSs). We identified three statistically significant ( p < 0.05) NPC1-specific variables associated with post-VFSS interpretive measures, providing insights into disease progression and treatment effects. Inter-rater reliability correlations for ASHA-NOMS and NIH-PAS demonstrated strong agreement between two speech pathologists [ASHA-NOMS: 0.76 (95% CI 0.70-0.83); NIH-PAS: 0.88 (95% CI 0.82- 0.93)]. VFSS mean radiation dosage was calculated ( n = 129) and fell within the acceptable range declared by the American College of Radiology (263.79 ± 147.44 cGy*cm 2 ). Conclusions This comprehensive methodology successfully documented functional swallowing status with dietary modifications and aspiration risk in a rare disease cohort (NPC1). Additionally, we effectively employed this methodology to support swallowing function as a research endpoint, specifically for phenotyping and developing therapeutic interventions for rare diseases.