Importance of Decisional Context in the Health Technology Assessment (HTA) of Ultra-Orphan Drugs
Author(s)
Krzysztof Kloc, MSc1, Mondher Toumi, Sr., MSc, PhD, MD2, Malwina Kowalska, MSc1.
1Clever-Access, Krakow, Poland, 2University Aix-Marseille /Creativ-Ceutical, Paris, France.
1Clever-Access, Krakow, Poland, 2University Aix-Marseille /Creativ-Ceutical, Paris, France.
OBJECTIVES: Clinical data quality and efficacy are key Health Technology Assessment (HTA) drivers. The disease context, including disease severity and the level of unmet needs, is also important, especially in ultra-rare diseases. However, the European HTA (EU-HTA) regulations do not account for disease-related considerations. This study aimed to analyze the evidence level for ultra-orphan drugs (UODs), the disease context and the associated HTA outcomes of the French HTA agency. Practical implications of the EU-HTA were also discussed.
METHODS: UODs with HTA reports in France were extracted from the NaviHTA database. Evidence level was assessed considering clinical study type, the comparator and outcome data relevance. HAS benefit assessment was analyzed against disease characteristics, including population age, severity, availability of alternatives, and the level of unmet needs.
RESULTS: Among the analyzed 68 UODs, 44% were assessed based on non-randomized studies, 34% had no comparative data, and only 21% had a relevant comparator. In most cases (79%), efficacy was not demonstrated with validated surrogate or non-surrogate endpoints, and often, the effect on mortality or patient-reported outcomes was insignificant (in 94% and 92% of cases, respectively). In 82% of cases, the disease was life-threatening. For most UODs (79%), there were therapeutic alternatives available; however, unmet needs were claimed moderate or high in 94% of cases. Ultimately, 75% of UODs were reimbursed, with 61% providing at least minor clinical improvement. Pediatric indications were associated with increased actual benefit (SMR) ratings, while life-threatening diseases and those without alternative therapy or higher unmet needs - with better improvement in benefit (ASMR) ratings.
CONCLUSIONS: UODs often demonstrate poor clinical evidence but are frequently accepted for reimbursement due to consideration of the disease context in the deliberative process. Decontextualized EU-HTA assessments could negatively impact HTA outcomes, which could limit patient access and suggest the exclusion of UODs from the EU centralized process.
METHODS: UODs with HTA reports in France were extracted from the NaviHTA database. Evidence level was assessed considering clinical study type, the comparator and outcome data relevance. HAS benefit assessment was analyzed against disease characteristics, including population age, severity, availability of alternatives, and the level of unmet needs.
RESULTS: Among the analyzed 68 UODs, 44% were assessed based on non-randomized studies, 34% had no comparative data, and only 21% had a relevant comparator. In most cases (79%), efficacy was not demonstrated with validated surrogate or non-surrogate endpoints, and often, the effect on mortality or patient-reported outcomes was insignificant (in 94% and 92% of cases, respectively). In 82% of cases, the disease was life-threatening. For most UODs (79%), there were therapeutic alternatives available; however, unmet needs were claimed moderate or high in 94% of cases. Ultimately, 75% of UODs were reimbursed, with 61% providing at least minor clinical improvement. Pediatric indications were associated with increased actual benefit (SMR) ratings, while life-threatening diseases and those without alternative therapy or higher unmet needs - with better improvement in benefit (ASMR) ratings.
CONCLUSIONS: UODs often demonstrate poor clinical evidence but are frequently accepted for reimbursement due to consideration of the disease context in the deliberative process. Decontextualized EU-HTA assessments could negatively impact HTA outcomes, which could limit patient access and suggest the exclusion of UODs from the EU centralized process.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HTA198
Topic
Health Policy & Regulatory, Health Technology Assessment, Organizational Practices
Topic Subcategory
Decision & Deliberative Processes, Value Frameworks & Dossier Format
Disease
Rare & Orphan Diseases