Single-Arm Trials and Reimbursement Decision Making in Europe: A Case Study in Non-Small Cell Lung Cancer
Author(s)
Giles Monnickendam, BSc, MSc.
Director, Ceelos Consulting, London, United Kingdom.
Director, Ceelos Consulting, London, United Kingdom.
OBJECTIVES: Single-arm trials (SAT) have been accepted as pivotal evidence for oncology marketing authorisations, with the objective of expediting regulatory approval and accelerating access to new therapies in areas of high unmet need. However, SATs do not provide the comparative evidence needed for robust value assessment by health technology assessment (HTA) bodies which determine reimbursement in Europe. This research examines regulatory and HTA outcomes in non-small cell lung cancer (NSCLC), to estimate the overall impact of SATs on access in Europe.
METHODS: European Medicines Authority (EMA) data was used to identify all regulatory submissions for NSCLC therapies. EMA public assessment reports and decision documents published by HTA bodies in France, Germany and UK were reviewed to identify therapies approved based on SATs, evidence assessed and decisions made in regulatory and reimbursement processes.
RESULTS: Of 20 NSCLC therapies submitted to the EMA with pivotal evidence from SATs, none has positive evidence for overall survival (OS) from subsequent randomised controlled trials (RCT) in the original SAT indication and only two have positive evidence for OS in any NSCLC indication. Of 15 therapies assessed by HAS (France), 5 received SMR “insufficient” and only one achieved better than ASMR5 using SAT evidence. Of 16 therapies assessed by G-BA (Germany), 14 had additional benefit not proven. Of 19 therapies considered by NICE (UK), 4 entered the Cancer Drugs Fund, 3 were not recommended and 6 appraisals were terminated or suspended. Re-evaluation using confirmatory RCTs improved some HTA value assessments but always caveated with high uncertainty.
CONCLUSIONS: Lack of comparative data in SATs and confounding from crossover in confirmatory RCTs present major impediments to value assessment of therapies first approved based on SATs. Because of these challenges, it is not obvious that increased reliance on SATs by oncology developers will deliver faster or better access to innovative medicines in Europe.
METHODS: European Medicines Authority (EMA) data was used to identify all regulatory submissions for NSCLC therapies. EMA public assessment reports and decision documents published by HTA bodies in France, Germany and UK were reviewed to identify therapies approved based on SATs, evidence assessed and decisions made in regulatory and reimbursement processes.
RESULTS: Of 20 NSCLC therapies submitted to the EMA with pivotal evidence from SATs, none has positive evidence for overall survival (OS) from subsequent randomised controlled trials (RCT) in the original SAT indication and only two have positive evidence for OS in any NSCLC indication. Of 15 therapies assessed by HAS (France), 5 received SMR “insufficient” and only one achieved better than ASMR5 using SAT evidence. Of 16 therapies assessed by G-BA (Germany), 14 had additional benefit not proven. Of 19 therapies considered by NICE (UK), 4 entered the Cancer Drugs Fund, 3 were not recommended and 6 appraisals were terminated or suspended. Re-evaluation using confirmatory RCTs improved some HTA value assessments but always caveated with high uncertainty.
CONCLUSIONS: Lack of comparative data in SATs and confounding from crossover in confirmatory RCTs present major impediments to value assessment of therapies first approved based on SATs. Because of these challenges, it is not obvious that increased reliance on SATs by oncology developers will deliver faster or better access to innovative medicines in Europe.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HPR184
Topic
Health Policy & Regulatory
Topic Subcategory
Reimbursement & Access Policy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Oncology