Evaluating the Role of Disease-Specific Patient-Reported Outcomes in HTA Submissions for Rare Conditions: A Comparative Case Study of Narcolepsy and Phenylketonuria
Author(s)
Veena Lim, MD, MSc, Minoo Mazaheri, PharmD, MPH, MSc, Laura Sawyer, MSc, Bryony Langford, MPhil, MSc.
Symmetron Limited, London, United Kingdom.
Symmetron Limited, London, United Kingdom.
OBJECTIVES: In rare diseases, disease-specific patient-reported outcomes (dsPROs) are important for capturing outcomes and patient experiences that generic tools can miss. However, their influence on HTA decisions remains unclear. This study examined narcolepsy and phenylketonuria, two conditions where key symptoms can be overlooked by generic tools, to explore the influence of dsPROs on HTA decisions.
METHODS: Public HTA dossiers for narcolepsy and phenylketonuria were reviewed across seven agencies. Data were extracted on dsPROs use, their role in clinical and economic evidence, and related committee commentary. Influence was qualitatively rated based on use and relevance to final decisions.
RESULTS: Among 24 submissions, dsPROs were included more consistently in narcolepsy (12/14) than in phenylketonuria (4/10). dsPROs had high influence on decisions in three narcolepsy submissions, but not in phenylketonuria. In narcolepsy, dsPROs were mostly used as primary trial endpoints and, in three cases, incorporated into economic models. One case mapped Epworth Sleepiness Scale (ESS) to EQ-5D despite collecting EQ-5D-5L data, citing the generic tool’s insensitivity to narcolepsy impact. In contrast, in phenylketonuria, dsPROs were not used in modelling. Despite sponsor efforts to include such measures in clinical sections, their influence was limited as HTA bodies frequently raised concerns about psychometric validation and relevance in the phenylketonuria population. HTA agency acceptance varied. CADTH and IQWiG applied stricter standards, often excluding dsPROs from benefit assessments due to methodological concerns. Interestingly, in one case (CADTH-SR0141-000), inclusion of a dsPRO led to a failure to demonstrate cost-effectiveness. NICE occasionally accepted mapped dsPROs but questioned their validity, particularly when preference-based measures were collected but not used. HAS accepted dsPROs as supportive evidence without major critique when no better validated tools or endpoints were available.
CONCLUSIONS: Including dsPROs can strengthen the completeness of evidence, but consideration should be given to the intended purpose and the specific expectations of the target HTA agency.
METHODS: Public HTA dossiers for narcolepsy and phenylketonuria were reviewed across seven agencies. Data were extracted on dsPROs use, their role in clinical and economic evidence, and related committee commentary. Influence was qualitatively rated based on use and relevance to final decisions.
RESULTS: Among 24 submissions, dsPROs were included more consistently in narcolepsy (12/14) than in phenylketonuria (4/10). dsPROs had high influence on decisions in three narcolepsy submissions, but not in phenylketonuria. In narcolepsy, dsPROs were mostly used as primary trial endpoints and, in three cases, incorporated into economic models. One case mapped Epworth Sleepiness Scale (ESS) to EQ-5D despite collecting EQ-5D-5L data, citing the generic tool’s insensitivity to narcolepsy impact. In contrast, in phenylketonuria, dsPROs were not used in modelling. Despite sponsor efforts to include such measures in clinical sections, their influence was limited as HTA bodies frequently raised concerns about psychometric validation and relevance in the phenylketonuria population. HTA agency acceptance varied. CADTH and IQWiG applied stricter standards, often excluding dsPROs from benefit assessments due to methodological concerns. Interestingly, in one case (CADTH-SR0141-000), inclusion of a dsPRO led to a failure to demonstrate cost-effectiveness. NICE occasionally accepted mapped dsPROs but questioned their validity, particularly when preference-based measures were collected but not used. HAS accepted dsPROs as supportive evidence without major critique when no better validated tools or endpoints were available.
CONCLUSIONS: Including dsPROs can strengthen the completeness of evidence, but consideration should be given to the intended purpose and the specific expectations of the target HTA agency.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
PCR83
Topic
Health Technology Assessment, Patient-Centered Research
Topic Subcategory
Patient-reported Outcomes & Quality of Life Outcomes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Rare & Orphan Diseases