FROM EVIDENCE GAPS TO LAUNCH READINESS: WHICH EVIDENCE UNCERTAINTIES RESTRICT PATIENT ACCESS?
Author(s)
Laurie M. Marlow, Biological Sciences (BSc), Sonika Awasthy, International Health Management (MSc).
HEOR & Market Access, OPEN Health, London, United Kingdom.
HEOR & Market Access, OPEN Health, London, United Kingdom.
OBJECTIVES: With the EU Joint Clinical Assessment (JCA) centralising comparative effectiveness expectations across Europe, evidence requirements need to be anticipated earlier in launch planning. This study explored a sample of recent restricted reimbursement decisions across major European HTA bodies, with the aim to identify evidence uncertainties to inform integrated evidence generation planning and launch readiness.
METHODS: Data was extracted from 20 publicly available HTA assessments (5 from each of NICE, G-BA, HAS, ZIN between 2020-2026; 12 oncology, 8 rare disease, selected as therapy areas common to HTA scrutiny and evidence uncertainty). AI-assisted text analysis supported extraction and coding of data against 12 predefined evidence-uncertainty categories, 25% of coded decisions were manually validated against source documents. Frequencies and proportions were calculated overall, by agency, and by therapeutic area.
RESULTS: The most frequent uncertainties relate to long-term outcomes (17/20) and patient-reported outcomes (17/20), HRQoL (16/20), comparative effectiveness (14/20), and subgroup uncertainty (13/20). Reimbursement outcomes were agency-specific: NICE used managed-access/Cancer Drugs Fund routes (5/5); ZIN required price negotiation via the sluis procedure (5/5); HAS granted favourable reimbursement with low-to-moderate clinical value (CAV III-V) (5/5); G-BA outcomes were subgroup- or time-dependent in 3/5 cases. Rare disease decisions showed higher rates of indirect-comparison, subgroup, and comparative-effectiveness uncertainty (each 87.5% vs 41.7-58.3% oncology); immature survival data were more common in oncology (66.7% vs 37.5%). Post-launch evidence-generation was specified in 75% (15/20) of decisions, most commonly through registry/real-world evidence and long-term follow-up (each 50%).
CONCLUSIONS: Long-term outcomes, patient-reported outcomes, HRQoL, and comparative effectiveness were the most recurrent uncertainties across NICE, G-BA, HAS and ZIN, with comparator and subgroup evidence disproportionately challenging in rare diseases. These findings support earlier planning for long-term outcomes, comparative evidence, patient-centred outcomes and subgroup evidence ahead of launch, particularly as JCA centralises comparative-effectiveness expectations across Europe.
METHODS: Data was extracted from 20 publicly available HTA assessments (5 from each of NICE, G-BA, HAS, ZIN between 2020-2026; 12 oncology, 8 rare disease, selected as therapy areas common to HTA scrutiny and evidence uncertainty). AI-assisted text analysis supported extraction and coding of data against 12 predefined evidence-uncertainty categories, 25% of coded decisions were manually validated against source documents. Frequencies and proportions were calculated overall, by agency, and by therapeutic area.
RESULTS: The most frequent uncertainties relate to long-term outcomes (17/20) and patient-reported outcomes (17/20), HRQoL (16/20), comparative effectiveness (14/20), and subgroup uncertainty (13/20). Reimbursement outcomes were agency-specific: NICE used managed-access/Cancer Drugs Fund routes (5/5); ZIN required price negotiation via the sluis procedure (5/5); HAS granted favourable reimbursement with low-to-moderate clinical value (CAV III-V) (5/5); G-BA outcomes were subgroup- or time-dependent in 3/5 cases. Rare disease decisions showed higher rates of indirect-comparison, subgroup, and comparative-effectiveness uncertainty (each 87.5% vs 41.7-58.3% oncology); immature survival data were more common in oncology (66.7% vs 37.5%). Post-launch evidence-generation was specified in 75% (15/20) of decisions, most commonly through registry/real-world evidence and long-term follow-up (each 50%).
CONCLUSIONS: Long-term outcomes, patient-reported outcomes, HRQoL, and comparative effectiveness were the most recurrent uncertainties across NICE, G-BA, HAS and ZIN, with comparator and subgroup evidence disproportionately challenging in rare diseases. These findings support earlier planning for long-term outcomes, comparative evidence, patient-centred outcomes and subgroup evidence ahead of launch, particularly as JCA centralises comparative-effectiveness expectations across Europe.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HTA25
Topic
Clinical Outcomes, Economic Evaluation, Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes
Disease
Oncology, Rare & Orphan Diseases