Optimizing PICO Scoping in EU HTA: Lessons From a HTA Coordination Group PICO Exercise in Advanced NSCLC to Inform Future Best Practice
Author(s)
Nebibe Varol, PhD1, Reginald Villacorta, BS, MA, MS, PhD2, Max Prokopovich, PharmD2, Adam Lee, MSc3, Ana Lisica, PhD4, Adam Parnaby, BA, MSc5.
1Bristol Myers Squibb, Uxbridge, United Kingdom, 2Bristol Myers Squibb, Lawrenceville, NJ, USA, 3Bristol Myers Squibb (affiliation at time of study), Uxbridge, United Kingdom, 4IQVIA, London, United Kingdom, 5Bristol Myers Squibb, Brussels, Belgium.
1Bristol Myers Squibb, Uxbridge, United Kingdom, 2Bristol Myers Squibb, Lawrenceville, NJ, USA, 3Bristol Myers Squibb (affiliation at time of study), Uxbridge, United Kingdom, 4IQVIA, London, United Kingdom, 5Bristol Myers Squibb, Brussels, Belgium.
OBJECTIVES: Following intense debate on the design of the EU HTA Regulation, PICO exercises were carried out by the HTACG to test the new JCA scoping process guidance. In this study, we aimed to review consolidated PICOs proposed for adagrasib to integrate developers perspective based on broader clinical evidence base and epidemiological insights from adagrasib HTA submissions and inform future best practices for scoping.
METHODS: We systematically reviewed the consolidated PICOs with respect to i) relevance of the different populations based on the approved indication and the target patient population in the pivotal trial KRYSTAL-1 and KRYSTAL -12 (confirmatory head-to-head trial) and ii) clinical relevance of comparators in each PICO based on precise target population, current national/EU level treatment guidelines, and clinical feedback during HTA assessments within KRAS G12C-mutated NSCLC in the UK/Europe.
RESULTS: The clinical relevance of 3 comparators (PICO 2,4,5) was unclear since 98.3% and 100% of patients had received prior IO and PDC in KRYSTAL-1 and KRYSTAL-12 studies respectively. These patients would not be rechallenged with ICI or PDC. The clinical relevance of 3 populations (PICO 6,11,12) was also unclear since both KRYSTAL studies excluded patients with only prior IO or only cytotoxic chemotherapy. Although EMA indication is broad enough for use after at least one prior systemic therapy, the relevance of this small population is unclear. PICO7,8 were identified as redundant and would have likely been removed in the final consolidation of JCA scoping.
CONCLUSIONS: Given the lack of systematic involvement of developers in JCA scoping, we appreciate the opportunity to learn from these PICO exercises. Streamlining assessment scope can be achieved through input from developers and clinical experts; thereby, ensuring process efficiency and usability at the national level. This is especially valuable in cases with high number of consolidated PICOs and complex evidence requirements.
METHODS: We systematically reviewed the consolidated PICOs with respect to i) relevance of the different populations based on the approved indication and the target patient population in the pivotal trial KRYSTAL-1 and KRYSTAL -12 (confirmatory head-to-head trial) and ii) clinical relevance of comparators in each PICO based on precise target population, current national/EU level treatment guidelines, and clinical feedback during HTA assessments within KRAS G12C-mutated NSCLC in the UK/Europe.
RESULTS: The clinical relevance of 3 comparators (PICO 2,4,5) was unclear since 98.3% and 100% of patients had received prior IO and PDC in KRYSTAL-1 and KRYSTAL-12 studies respectively. These patients would not be rechallenged with ICI or PDC. The clinical relevance of 3 populations (PICO 6,11,12) was also unclear since both KRYSTAL studies excluded patients with only prior IO or only cytotoxic chemotherapy. Although EMA indication is broad enough for use after at least one prior systemic therapy, the relevance of this small population is unclear. PICO7,8 were identified as redundant and would have likely been removed in the final consolidation of JCA scoping.
CONCLUSIONS: Given the lack of systematic involvement of developers in JCA scoping, we appreciate the opportunity to learn from these PICO exercises. Streamlining assessment scope can be achieved through input from developers and clinical experts; thereby, ensuring process efficiency and usability at the national level. This is especially valuable in cases with high number of consolidated PICOs and complex evidence requirements.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HTA260
Topic
Health Technology Assessment
Disease
Oncology