EVIDENCE EXPECTATIONS VS. EVIDENTIARY REALITY: LESSONS FROM MISSING INFORMATION NOTICES IN RARE ONCOLOGY JOINT CLINICAL ASSESSMENTS
Author(s)
Rachel Beckerman, PhD1, Chloe Sheppard, MSc2, James Horscroft, PhD1, Sylwia Lach, MPH3, Helena Emich, PhD4.
1Maple Health Group, New York, NY, USA, 2Maple Health Group, London, United Kingdom, 3Maple Health Group, LLC, Cracow, Poland, 4Maple Health Group, New York, United Kingdom.
1Maple Health Group, New York, NY, USA, 2Maple Health Group, London, United Kingdom, 3Maple Health Group, LLC, Cracow, Poland, 4Maple Health Group, New York, United Kingdom.
OBJECTIVES: To evaluate the evidence requirements imposed under the Joint Clinical Assessment (JCA) and assess their feasibility for rare oncology therapies, using Missing Information Notices (MINs) as a structured data source.
METHODS: We conducted a qualitative analysis of two publicly available MINs issued by the European Commission: one for catequentinib (issued May 2026) and one for autologous melanoma-derived tumor infiltrating lymphocytes (TIL) (issued February 2026). In both cases, the JCA was discontinued. The information gaps cited in the MINs were categorised by the relevant article under EU Regulation 2021/2282 and consolidated into key themes.
RESULTS: Both MINs represented second requests for evidence from the European Commission, meaning developers had made an initial dossier submission and one round of remediation before the notices were issued. The information gaps centered around six key themes: incomplete systematic evidence retrieval across data sources; insufficient methodological justification for deviations from Health Technology Assessment Coordination Group (HTA CG) guidance; absent or inadequate comparative effectiveness and safety data across multiple Populations, Interventions, Comparators and Outcomes (PICOs); non-compliance with dossier template structure; absence of underlying documentation including statistical analysis plans, and incomplete certainty-of-evidence assessments. Information gaps across both MINs were flagged for non-adherence to Articles 9(2), 9(3)(a-d), and 9(4), indicating the breadth and complexity of JCA requirements.
CONCLUSIONS: The extent and recurring nature of the information gaps identified in the MINs for catequentinib and autologous melanoma-derived TIL reflect the high evidence expectations for JCAs in a rare oncology setting where evidence bases are inherently limited. The requirement to satisfy these standards under tight timelines represents a substantial operational and resource burden for developers. To avoid additional failed JCAs in future, there is a need for early evidence generation and contingency planning by developers, meaningful dialogue between developers and JCA assessors, and a pragmatic JCA framework that acknowledges evidentiary constraints in rare diseases.
METHODS: We conducted a qualitative analysis of two publicly available MINs issued by the European Commission: one for catequentinib (issued May 2026) and one for autologous melanoma-derived tumor infiltrating lymphocytes (TIL) (issued February 2026). In both cases, the JCA was discontinued. The information gaps cited in the MINs were categorised by the relevant article under EU Regulation 2021/2282 and consolidated into key themes.
RESULTS: Both MINs represented second requests for evidence from the European Commission, meaning developers had made an initial dossier submission and one round of remediation before the notices were issued. The information gaps centered around six key themes: incomplete systematic evidence retrieval across data sources; insufficient methodological justification for deviations from Health Technology Assessment Coordination Group (HTA CG) guidance; absent or inadequate comparative effectiveness and safety data across multiple Populations, Interventions, Comparators and Outcomes (PICOs); non-compliance with dossier template structure; absence of underlying documentation including statistical analysis plans, and incomplete certainty-of-evidence assessments. Information gaps across both MINs were flagged for non-adherence to Articles 9(2), 9(3)(a-d), and 9(4), indicating the breadth and complexity of JCA requirements.
CONCLUSIONS: The extent and recurring nature of the information gaps identified in the MINs for catequentinib and autologous melanoma-derived TIL reflect the high evidence expectations for JCAs in a rare oncology setting where evidence bases are inherently limited. The requirement to satisfy these standards under tight timelines represents a substantial operational and resource burden for developers. To avoid additional failed JCAs in future, there is a need for early evidence generation and contingency planning by developers, meaningful dialogue between developers and JCA assessors, and a pragmatic JCA framework that acknowledges evidentiary constraints in rare diseases.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HTA115
Topic
Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes, Systems & Structure, Value Frameworks & Dossier Format
Disease
Oncology, Rare & Orphan Diseases