BEYOND UNCERTAINTY: A CROSS-AGENCY REVIEW OF HTA APPRAISALS OF EARLY-PHASE TRIALS IN ANSCLC
Author(s)
Urshita Pandit, MSc1, Noemi Muszbek, MSc2, Federico Manevy, MSc3, kostas papadakis, MSc, MBA3.
1Visible Analytics Ltd, Oxford, United Kingdom, 2Visible Analytics Ltd, Reading, United Kingdom, 3Bayer Consumer Care AG, Basel, Switzerland.
1Visible Analytics Ltd, Oxford, United Kingdom, 2Visible Analytics Ltd, Reading, United Kingdom, 3Bayer Consumer Care AG, Basel, Switzerland.
OBJECTIVES: Early-phase trials are increasingly used for regulatory approval; however, health technology assessment (HTA) agencies frequently highlight uncertainties affecting reimbursement. Understanding how these uncertainties are addressed can inform evidence-generation and submission strategies. This study aimed to identify key uncertainties raised in HTAs informed by early-phase trials, and the approaches used to address them, in advanced non-small cell lung cancer (aNSCLC).
METHODS: A literature review was conducted of aNSCLC appraisals published between 2022 and 2026 by the National Institute for Health and Care Excellence, Scottish Medicines Consortium, and Canada’s Drug Agency. Key appraisal characteristics and HTA concerns and solutions related to early-phase trials were extracted. Findings were analysed qualitatively to identify common themes.
RESULTS: Of 43 appraisals (19 treatments), 25 (58%) used early-phase evidence (48% phase 1, 52% phase 2 trials). Among appraisals based on early-phase evidence, 68% resulted in a positive recommendation, similar to all appraisals (70%). The recommendation rate based on early-phase evidence was highest for NICE (73%) and lowest for CDA (63%); across all appraisals, it was highest for CDA (80%) and lowest for SMC (58%). Most of these appraisals (92%) used a partitioned survival model. Common concerns included immature data, uncertainty in long-term outcomes, challenges with indirect comparisons, and limited generalisability. Concerns raised by HTA agencies were broadly similar, differing mainly in emphasis and analytical preferences, e.g. NICE’s focus on treatment waning and CDA’s focus on modelling approach. Uncertainty appeared partly mitigated when transparently characterised and supported by clearly described complementary analyses, including clinical validation, use of external or real-world data, and extensive sensitivity analyses.
CONCLUSIONS: HTA decisions were driven not by absence of uncertainty, but by how it was characterised, contextualised, and supported. Transparent and well-justified analytical approaches enabled decision-making despite residual uncertainty, underscoring the importance of robust evidentiary strategies when early-phase data underpin submissions.
METHODS: A literature review was conducted of aNSCLC appraisals published between 2022 and 2026 by the National Institute for Health and Care Excellence, Scottish Medicines Consortium, and Canada’s Drug Agency. Key appraisal characteristics and HTA concerns and solutions related to early-phase trials were extracted. Findings were analysed qualitatively to identify common themes.
RESULTS: Of 43 appraisals (19 treatments), 25 (58%) used early-phase evidence (48% phase 1, 52% phase 2 trials). Among appraisals based on early-phase evidence, 68% resulted in a positive recommendation, similar to all appraisals (70%). The recommendation rate based on early-phase evidence was highest for NICE (73%) and lowest for CDA (63%); across all appraisals, it was highest for CDA (80%) and lowest for SMC (58%). Most of these appraisals (92%) used a partitioned survival model. Common concerns included immature data, uncertainty in long-term outcomes, challenges with indirect comparisons, and limited generalisability. Concerns raised by HTA agencies were broadly similar, differing mainly in emphasis and analytical preferences, e.g. NICE’s focus on treatment waning and CDA’s focus on modelling approach. Uncertainty appeared partly mitigated when transparently characterised and supported by clearly described complementary analyses, including clinical validation, use of external or real-world data, and extensive sensitivity analyses.
CONCLUSIONS: HTA decisions were driven not by absence of uncertainty, but by how it was characterised, contextualised, and supported. Transparent and well-justified analytical approaches enabled decision-making despite residual uncertainty, underscoring the importance of robust evidentiary strategies when early-phase data underpin submissions.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HTA27
Topic
Economic Evaluation, Health Technology Assessment, Study Approaches
Topic Subcategory
Decision & Deliberative Processes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Oncology