WHEN EVIDENCE IS NON-RANDOMIZED: HTA DECISIONS IN ATMPS ASSESSMENTS. A CROSS-AGENCY TARGETED REVIEW
Author(s)
Adéla Bártová, MSc, PharmD1, Beatriz Carmona-Hidalgo, PhD2, Md Sohail Aman, MD3, Hodgkinson Victoria, PhD4, Monica Daigl, MSc5.
1Masaryk University Brno, Czech republic, Brno, Czech Republic, 2Junta De Andalucia, Cordoba, Spain, 3PharmaQuant, Kolkata, India, 4Lumiio, Calgary, AB, Canada, 5Access Evidence Enabler, Roche, Basle, Switzerland.
1Masaryk University Brno, Czech republic, Brno, Czech Republic, 2Junta De Andalucia, Cordoba, Spain, 3PharmaQuant, Kolkata, India, 4Lumiio, Calgary, AB, Canada, 5Access Evidence Enabler, Roche, Basle, Switzerland.
OBJECTIVES: Non-randomized evidence (NRE) form a significant evidence base for advanced therapy medicinal products (ATMPs), especially in rare diseases where randomized trials are often not feasible. Despite regulatory acceptance, HTA agencies frequently interpret NRE evidence inconsistently. This study compares assessments across five major agencies (CDA, G-BA, HAS, ICER, and NICE) and identifies decision-making patterns to inform expectations for evidence generation. This work was developed in collaboration with the HTAi Rare Disease Interest Group.
METHODS: A targeted review was conducted using predefined criteria. ATMPs approved based on NRE were identified from the EMA and FDA regulatory databases. For each product, assessment outcome (eg positive, conditional, or unfavourable), key arguments and methodological approaches were extracted and quality check performed. A descriptive analysis synthesis of cross-agency patterns was performed and outcomes visualized with heat maps.
RESULTS: Thirteen ATMPs were identified across the oncological, hematological and nervous system areas, representing a total of 81 recommendations across agencies and indications. In 88% of the assessments, agencies explicitly indicated SAT design as a limitation and 21% (17/81) resulted in negative outcomes (p=0.620 for cross-agency comparison). HTA benefit ratings varied across agencies with ICER having more positive assessments as opposed to other agencies (p-value<0.001). Comparative effectiveness was assessed in 72% of cases based on comparator’s aggregated level data (eg using MAIC or STC), 13% of the comparisons with SoC were derived based on individual patient data (eg with PSM), 4% of the assessments relied on intra-patient comparison and in 12% the assessments no comparative effectiveness was supplemented.
CONCLUSIONS: HTA agencies’ decisions on NRE-based ATMPs differ substantially. The findings further suggest that, without clearer expectations regarding acceptable levels of uncertainty, NREs-based ATMPs will continue to face considerable variability in HTA outcomes - directly affecting the predictability of patient access to innovative treatments.
METHODS: A targeted review was conducted using predefined criteria. ATMPs approved based on NRE were identified from the EMA and FDA regulatory databases. For each product, assessment outcome (eg positive, conditional, or unfavourable), key arguments and methodological approaches were extracted and quality check performed. A descriptive analysis synthesis of cross-agency patterns was performed and outcomes visualized with heat maps.
RESULTS: Thirteen ATMPs were identified across the oncological, hematological and nervous system areas, representing a total of 81 recommendations across agencies and indications. In 88% of the assessments, agencies explicitly indicated SAT design as a limitation and 21% (17/81) resulted in negative outcomes (p=0.620 for cross-agency comparison). HTA benefit ratings varied across agencies with ICER having more positive assessments as opposed to other agencies (p-value<0.001). Comparative effectiveness was assessed in 72% of cases based on comparator’s aggregated level data (eg using MAIC or STC), 13% of the comparisons with SoC were derived based on individual patient data (eg with PSM), 4% of the assessments relied on intra-patient comparison and in 12% the assessments no comparative effectiveness was supplemented.
CONCLUSIONS: HTA agencies’ decisions on NRE-based ATMPs differ substantially. The findings further suggest that, without clearer expectations regarding acceptable levels of uncertainty, NREs-based ATMPs will continue to face considerable variability in HTA outcomes - directly affecting the predictability of patient access to innovative treatments.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HTA282
Topic
Health Policy & Regulatory, Health Technology Assessment, Organizational Practices
Topic Subcategory
Decision & Deliberative Processes, Value Frameworks & Dossier Format
Disease
Rare & Orphan Diseases