OBJECTIVES: Ahead of the mandatory EU Joint Clinical Assessment (JCA) for first-indication oncology projects in 2025, the JCA scoping process was simulated to explore the impact of different treatment landscapes on the number of populations, interventions, comparators and outcomes (PICOs) generated.

METHODS: Scoping was simulated for avelumab, an oncology therapy approved by the EMA in the densely populated renal cell carcinoma (RCC) and sparsely populated, rare Merkel cell carcinoma (MCC) indications. Targeted searches of EU HTA bodies were conducted to find publicly available appraisals for both indications; PICOs derived from these appraisals were consolidated in accordance with EUnetHTA21 scoping guidance. National and European guidelines were also reviewed to assess their impact on the total number of PICOs.

RESULTS: Reviewing 9 appraisals for RCC and 6 for MCC yielded 24 and 9 PICOs, respectively, pre-consolidation. Consolidation generated 22 and 8 PICOs for RCC and MCC, respectively. Of these consolidated PICOs, 12 and 2 were only required by a single member state for RCC and MCC respectively. Many comparators identified in guidelines were not reflected in national appraisals; upon including guidelines, an additional 8 and 6 comparators were identified for RCC and MCC, respectively, raising the number of consolidated PICOs to 53 and 21.

CONCLUSIONS: Based on appraisals and guidelines, the crowded RCC indication expectedly produced a substantially higher number of PICOs than MCC, driven by a higher number of subpopulations (RCC: 9, MCC: 2) and comparators (RCC: 16, MCC: 12). Where not specified otherwise, it was conservatively assumed that all listed comparators were required; whilst prospectively examining guidelines could provide a comprehensive assessment of comparators, investigating pragmatic HTA decisions and discussing different member state requirements with affiliates could aid further PICO consolidation. Overall, this simulation exercise further highlights the challenges likely to face manufacturers in meeting evidence requirements for all identified PICOs.