Evolving perspectives on patient outcome measures for oncology medicines and ATMPs in Health Technology Assessment

Abstract

Abstract Background: The PICO (Population, Intervention, Comparator, Outcome) framework is widely used in Health Technology Assessment (HTA) to define the evaluation scope for medicines, and also plays a key role in Joint Clinical Assessments under the EU HTA Regulation. For the “Outcomes” element, variations in stakeholder perceptions and jurisdictional practices may result in differing priorities for outcome measures considered. This study evaluates the outcome measures considered by HTA organizations in relative effectiveness assessments (REAs) of oncology medicines, their differences from regulatory approvals by the European Medicines Agency (EMA), and variations across HTA organizations. Methods: We conducted a retrospective comparative analysis of outcome measures used in EMA marketing authorization assessments and REAs by HTA organizations across six European countries (Denmark, France, Germany, Ireland, The Netherlands, and The United Kingdom). The analysis focused on a selection of oncology medicines approved between 2010-2023. Outcome measures were extracted from publicly available HTA and EMA assessment reports and pooled into categories. We compared outcome measures considered in HTA assessments with those in EMA reports, as well as across HTA organizations. Results: We analyzed 155 HTA reports for 32 medicine-indication combinations, identifying 28 distinct outcome measures, with Overall Survival (OS), Progression-free Survival (PFS), and adverse events being the most frequently assessed. Of the HTA reports, 21 (14%) fully aligned with the outcome measures considered by EMA, 47 (30%) showed no alignment, and 75 (48%) showed partial alignment, considering either additional or fewer outcome measures. OS was included in all HTA assessments when considered by the EMA (100%), while alignment for PFS and Overall Response Rate (ORR) was 77% and 34%, respectively. Alignment between outcome measures considered by EMA and HTA organizations varied by country, ranging from 18% for Germany (G-BA) to 87% for Ireland (NCPE). Significant variability in outcome measures was observed across HTA organizations, with an average alignment of 72% the same medicine-indication combinations. Conclusion(s): Outcome measures considered by HTA organizations in REAs of oncology medicines vary from EMA regulatory evaluations as well as across organizations, posing challenges to the PICO scoping process within 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 evaluations.