Too Advanced for STA, Too Common for HST? Navigating NICE Appraisals of Gene Therapies
Author(s)
Evangelos Papastergios, PhD, Bryony Langford, MPhil, MSc, Laura Sawyer, BA, MSc.
Symmetron, London, United Kingdom.
Symmetron, London, United Kingdom.
OBJECTIVES: Gene therapies (GTs) offer transformative potential for severe conditions but face unique health technology assessment (HTA) challenges. This study compared GT evaluations through the Highly Specialised Technology (HST) and the Single Technology Appraisal (STA) routes, exploring decision drivers and implications for access.
METHODS: The NICE website was searched in June 2025 for completed appraisals of GTs. Extracted data included timelines, recommendations, evidence base and criticisms, value modifiers, and managed access agreements (MAAs). Appraisals were categorised by route (HST vs STA) and compared.
RESULTS: Seventeen HTAs of 12 GTs were identified, comprising 6 HST appraisals and 11 STAs. STAs were associated with shorter timelines from NICE submission to recommendation (STA: 12 months; HST: 15 months). Four HST appraisals resulted in a full recommendation, while two led to restricted recommendations based on age and disease severity. Outcomes were poorer for STAs, including six full, four restricted (based on age, contraindications and disease-specific criteria), and one negative recommendation. Few submissions included randomised controlled trials (HST: 1/6; STA: 3/11), with most relying on single-arm studies. However, STAs faced stricter scrutiny, particularly on trial design, model structure, survival extrapolation and generalisability. The HST route showed greater flexibility in the use of a 1.5% discount rate (HST: 2/6; STA: 0) and QALY weighting (HST: 5/6; STA: 5/11). MAAs were more common among STAs, with five using the Cancer Drugs Fund and three the Innovative Medicines Fund. Only one HST included an MAA. MAAs were primarily used to address uncertainty around long-term and real-world effectiveness.
CONCLUSIONS: While GTs have achieved access through both HST and STA pathways, these routes manage uncertainty differently. HSTs were more frequently associated with favourable discount rates, modifiers, and unrestricted recommendations. STAs faced tighter scrutiny of clinical evidence and economic assumptions, often resulting in restricted access and MAAs to address uncertainty.
METHODS: The NICE website was searched in June 2025 for completed appraisals of GTs. Extracted data included timelines, recommendations, evidence base and criticisms, value modifiers, and managed access agreements (MAAs). Appraisals were categorised by route (HST vs STA) and compared.
RESULTS: Seventeen HTAs of 12 GTs were identified, comprising 6 HST appraisals and 11 STAs. STAs were associated with shorter timelines from NICE submission to recommendation (STA: 12 months; HST: 15 months). Four HST appraisals resulted in a full recommendation, while two led to restricted recommendations based on age and disease severity. Outcomes were poorer for STAs, including six full, four restricted (based on age, contraindications and disease-specific criteria), and one negative recommendation. Few submissions included randomised controlled trials (HST: 1/6; STA: 3/11), with most relying on single-arm studies. However, STAs faced stricter scrutiny, particularly on trial design, model structure, survival extrapolation and generalisability. The HST route showed greater flexibility in the use of a 1.5% discount rate (HST: 2/6; STA: 0) and QALY weighting (HST: 5/6; STA: 5/11). MAAs were more common among STAs, with five using the Cancer Drugs Fund and three the Innovative Medicines Fund. Only one HST included an MAA. MAAs were primarily used to address uncertainty around long-term and real-world effectiveness.
CONCLUSIONS: While GTs have achieved access through both HST and STA pathways, these routes manage uncertainty differently. HSTs were more frequently associated with favourable discount rates, modifiers, and unrestricted recommendations. STAs faced tighter scrutiny of clinical evidence and economic assumptions, often resulting in restricted access and MAAs to address uncertainty.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HTA337
Topic
Clinical Outcomes, Health Policy & Regulatory, Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes, Value Frameworks & Dossier Format
Disease
Genetic, Regenerative & Curative Therapies, No Additional Disease & Conditions/Specialized Treatment Areas