Solving the PICO Puzzle: Perspectives on Outcome Measures for Oncology Medicines in Assessments of the European Medicines Agency and Health Technology Assessment Organizations in Europe
Author(s)
Francine Brinkhuis, MSc1, Kees-Jan van Hoorne, BSc2, Wim G. Goettsch, MSc, PhD1, Aukje K. Mantel-Teeuwisse, MSc, PhD2, Hendrika A. van den Ham, MSc, PhD2.
1Utrecht University; Zorginstituut Nederland, Utrecht; Diemen, Netherlands, 2Utrecht University, Utrecht, Netherlands.
1Utrecht University; Zorginstituut Nederland, Utrecht; Diemen, Netherlands, 2Utrecht University, Utrecht, Netherlands.
OBJECTIVES: The PICO (Population, Intervention, Comparator, Outcome) framework is widely used in Health Technology Assessment (HTA) to define the evaluation scope for medicines and is crucial in Joint Clinical Assessments under the EU HTA Regulation. For the “Outcomes” element, variations in stakeholder perceptions and jurisdictional practices may result in differences in outcome measures considered. This study examines outcome measures used in relative effectiveness assessments (REAs) of oncology medicines, their alignment with European Medicines Agency (EMA) approvals, and variation across HTA organizations.
METHODS: We conducted a retrospective analysis of outcome measures used in EMA marketing authorizations and REAs by HTA organizations across six European countries (Denmark, France, Germany, Ireland, The Netherlands, United Kingdom). The analysis focused on selected oncology medicines approved between 2010-2023. Outcome measures were extracted from publicly available reports, pooled into categories, and compared between EMA and HTA assessments as well as across HTA organizations.
RESULTS: A preliminary analysis of 155 HTA reports for 32 medicine-indication combinations identified 28 distinct outcome measures. Overall Survival (OS), Progression-free Survival (PFS), and adverse events were most frequently assessed. OS was included in all HTA assessments when considered by EMA (100%), while alignment for PFS and Overall Response Rate (ORR) was 77% and 34%, respectively. Alignment between EMA and HTA outcome measures varied by country, ranging from lowest in Germany to highest in Ireland. Significant variability in outcome measures was observed across HTA organizations. The results may be updated as final product selection is confirmed.
CONCLUSIONS: Outcome measures considered by HTA organizations in REAs of oncology medicines differ from EMA regulatory evaluations and vary across countries, posing challenges to PICO scoping under the EU HTA Regulation. These findings underscore the need for early regulatory-HTA collaboration, such as Joint Scientific Consultations, to align priorities and optimize clinical trial designs for more consistent and efficient assessments.
METHODS: We conducted a retrospective analysis of outcome measures used in EMA marketing authorizations and REAs by HTA organizations across six European countries (Denmark, France, Germany, Ireland, The Netherlands, United Kingdom). The analysis focused on selected oncology medicines approved between 2010-2023. Outcome measures were extracted from publicly available reports, pooled into categories, and compared between EMA and HTA assessments as well as across HTA organizations.
RESULTS: A preliminary analysis of 155 HTA reports for 32 medicine-indication combinations identified 28 distinct outcome measures. Overall Survival (OS), Progression-free Survival (PFS), and adverse events were most frequently assessed. OS was included in all HTA assessments when considered by EMA (100%), while alignment for PFS and Overall Response Rate (ORR) was 77% and 34%, respectively. Alignment between EMA and HTA outcome measures varied by country, ranging from lowest in Germany to highest in Ireland. Significant variability in outcome measures was observed across HTA organizations. The results may be updated as final product selection is confirmed.
CONCLUSIONS: Outcome measures considered by HTA organizations in REAs of oncology medicines differ from EMA regulatory evaluations and vary across countries, posing challenges to PICO scoping under the EU HTA Regulation. These findings underscore the need for early regulatory-HTA collaboration, such as Joint Scientific Consultations, to align priorities and optimize clinical trial designs for more consistent and efficient assessments.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HPR188
Topic
Clinical Outcomes, Health Policy & Regulatory, Health Technology Assessment
Topic Subcategory
Reimbursement & Access Policy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Oncology