METHODOLOGICAL FIT BETWEEN THE EU JOINT CLINICAL ASSESSMENT AND EVIDENCE GENERATION FOR ADVANCED THERAPY AND ORPHAN MEDICINES
Author(s)
Saurabh Aggarwal, BS, MS, PhD1, Ozlem Topaloglu, PhD, MPH2, Sushil Kumar, BS2.
1NOVEL Health Strategies, Chevy Chase, MD, USA, 2NOVEL Health Strategies, Bethesda, MD, USA.
1NOVEL Health Strategies, Chevy Chase, MD, USA, 2NOVEL Health Strategies, Bethesda, MD, USA.
OBJECTIVES: The EU Joint Clinical Assessment (JCA) requires evidence on relative effectiveness and safety across Member State PICO questions. Advanced therapy medicinal products (ATMPs) and orphan medicines often have small populations, limited comparator availability, single arm pivotal studies, surrogate outcomes and immature durability data at launch. We assessed how JCA evidence expectations align with the evidence base typically available for ATMPs and orphan medicines before the 2028 scope expansion
METHODS: We synthesized published JCA methodological and procedural guidance and evidence reviews of EU authorized ATMPs. Evidentiary features were extracted for trial design, comparator availability, endpoint maturity, use of external controls, indirect treatment comparisons and long term follow up. Features were mapped against JCA requirements for comparative evidence across PICO defined populations and comparators.
RESULTS: The evidence base for ATMPs and orphan medicines frequently relies on single arm trials, surrogate or intermediate endpoints, natural history data, external controls and post launch follow up. These features create challenges under a JCA framework centered on comparative estimates for each relevant population and comparator. A stakeholder analysis of 18 EU authorized ATMPs estimated that 16 would not have demonstrated added benefit under baseline methods proposed for JCA, mainly because randomized evidence or long term durability data were unavailable at launch. PICO multiplication may further widen evidence gaps when Member States identify multiple subpopulations or comparators not represented in pivotal trials. These risks are expected to increase when orphan medicines enter JCA scope in 2028 and all new medicines enter scope in 2030.
CONCLUSIONS: A methodological fit issue exists between JCA comparative evidence requirements and the evidence generation constraints of ATMPs and orphan medicines. Developers should seek early scientific advice, plan indirect or external control strategies prospectively, justify surrogate outcomes and define post launch durability evidence plans before JCA scope expansion.
METHODS: We synthesized published JCA methodological and procedural guidance and evidence reviews of EU authorized ATMPs. Evidentiary features were extracted for trial design, comparator availability, endpoint maturity, use of external controls, indirect treatment comparisons and long term follow up. Features were mapped against JCA requirements for comparative evidence across PICO defined populations and comparators.
RESULTS: The evidence base for ATMPs and orphan medicines frequently relies on single arm trials, surrogate or intermediate endpoints, natural history data, external controls and post launch follow up. These features create challenges under a JCA framework centered on comparative estimates for each relevant population and comparator. A stakeholder analysis of 18 EU authorized ATMPs estimated that 16 would not have demonstrated added benefit under baseline methods proposed for JCA, mainly because randomized evidence or long term durability data were unavailable at launch. PICO multiplication may further widen evidence gaps when Member States identify multiple subpopulations or comparators not represented in pivotal trials. These risks are expected to increase when orphan medicines enter JCA scope in 2028 and all new medicines enter scope in 2030.
CONCLUSIONS: A methodological fit issue exists between JCA comparative evidence requirements and the evidence generation constraints of ATMPs and orphan medicines. Developers should seek early scientific advice, plan indirect or external control strategies prospectively, justify surrogate outcomes and define post launch durability evidence plans before JCA scope expansion.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
P64
Topic
Health Policy & Regulatory
Topic Subcategory
Pricing Policy & Schemes, Reimbursement & Access Policy