ONE SIZE FITS ALL? RARE DISEASES AND ADVANCED THERAPIES UNDER THE EU JOINT CLINICAL ASSESSMENT FRAMEWORK
Author(s)
Imen Soussi, engineer1, Meriem Fadhel, engineer1, Aleksandra Caban, Phd2, Mondher Toumi, MSc, PhD, MD3.
1Clever-Access, Tunis, Tunisia, 2Clever-Access, Cracow, Poland, 3Aix-Marseille University, Marseille, France.
1Clever-Access, Tunis, Tunisia, 2Clever-Access, Cracow, Poland, 3Aix-Marseille University, Marseille, France.
OBJECTIVES: Rare-disease and advanced therapies increasingly drive innovation — yet they are assessed with a framework built for conventional medicines. The HTAR recognises their specific characteristics, but Joint Clinical Assessments operate primarily through a generic methodological approach. This study examined whether existing JCA procedures accommodate the evidence-generation realities of orphan medicinal products (OMPs) and advanced therapy medicinal products (ATMPs).
METHODS: A legal-policy and methodological analysis was performed using Regulation (EU) 2021/2282, orphan and ATMP legislation, HTA methodological guidance, and published evidence regarding evidence-generation pathways for rare diseases and advanced therapies. Particular focus was placed on the treatment of single-arm trials and unanchored indirect treatment comparisons.
RESULTS: The analysis identified a structural mismatch between the generic JCA framework and the evidentiary characteristics of many OMPs and ATMPs. Rare diseases often involve limited patient populations that restrict the feasibility of large randomised controlled trials. Advanced therapies frequently rely on single-arm evidence and long-term follow-up strategies. Simultaneously, current methodological expectations place substantial weight on comparative evidence and frequently challenge unanchored indirect comparisons. The combination of these factors may create circumstances in which therapies authorised through recognised regulatory pathways encounter difficulties demonstrating value within HTA assessments. Given the high prevalence of orphan designation among approved ATMPs and the growing role of orphan products in oncology, this issue affects a substantial segment of the future JCA portfolio.
CONCLUSIONS: A dedicated framework for rare diseases and advanced therapies could reflect how their evidence is actually generated, improving predictability and consistency without lowering scientific standards. Adaptation is not a concession; it is a precondition for fair assessment.
METHODS: A legal-policy and methodological analysis was performed using Regulation (EU) 2021/2282, orphan and ATMP legislation, HTA methodological guidance, and published evidence regarding evidence-generation pathways for rare diseases and advanced therapies. Particular focus was placed on the treatment of single-arm trials and unanchored indirect treatment comparisons.
RESULTS: The analysis identified a structural mismatch between the generic JCA framework and the evidentiary characteristics of many OMPs and ATMPs. Rare diseases often involve limited patient populations that restrict the feasibility of large randomised controlled trials. Advanced therapies frequently rely on single-arm evidence and long-term follow-up strategies. Simultaneously, current methodological expectations place substantial weight on comparative evidence and frequently challenge unanchored indirect comparisons. The combination of these factors may create circumstances in which therapies authorised through recognised regulatory pathways encounter difficulties demonstrating value within HTA assessments. Given the high prevalence of orphan designation among approved ATMPs and the growing role of orphan products in oncology, this issue affects a substantial segment of the future JCA portfolio.
CONCLUSIONS: A dedicated framework for rare diseases and advanced therapies could reflect how their evidence is actually generated, improving predictability and consistency without lowering scientific standards. Adaptation is not a concession; it is a precondition for fair assessment.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HPR97
Topic
Health Policy & Regulatory
Topic Subcategory
Approval & Labeling, Coverage with Evidence Development & Adaptive Pathways, Reimbursement & Access Policy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas