Table 1.

Evolving evidence challenges for a European health technology assessment in oncology as derived from the qualitative comments provided in the questionnaire

Management of Uncertainty	Comparator Choice	Endpoint Selection	Process Challenges
How can EU HTA take into account evolving clinical research and development paradigms in oncology to be a driver not a bottleneck for patient access to new medicines while at the same time not reducing quality standards? How to approach a gradually evolving evidence body with limited certainty at time of launch? How can certainty with small numbers e.g., in childhood cancer or in ATMPs be achieved? Is there a case for context-related evidence requirements & standards? What are suitable and achievable comparative evidence requirements for real-world data and new clinical trial designs? How relevant are the results of the pre-defined testing hierarchy (Alpha Risk Spending) to HTAs? How can combination of drugs be approached in HTA in terms of benefit per drug / shared benefit, etc.?	How to manage an ever more diverging and fast-moving comparator landscape in targeted oncology? How to ensure that comparator choice fulfils both, regulatory and HTA requirements? How to manage different national standards of care and heterogeneous guideline recommendations? Who should be involved in the selection of appropriate comparative therapy?	How to ensure that endpoints fulfil both, regulatory and HTA requirements? How to develop and validate innovative / new endpoints that best demonstrate the benefit of a new oncology medicine to patients? How to include patients and clinicians in the definition and selection of endpoints that are both, relevant for clinical trials and clinical practice? How to determine and develop valid and meaningful threshold for minimal clinical important difference? How to harmonize hierarchy of endpoints and measurement methods across regulatory and HTA bodies? How to align the EU HTA bodies on key oncology endpoints such as PFS?	How can regulatory and HTA requirements be coordinated and aligned? How to approach the challenge of multiple PICOs? How to achieve harmonization in implementation of EU HTAs while the assessments are not binding for national bodies? How can equal access of patients to new oncology medicines be facilitated despite the joint assessments not being binding? How to improve inclusion of eastern European countries in this process? How to quantify/ track the reduction of administrative burden? How do evolving regulatory pathways match HTA processes e.g., the upcoming new EMA regulation on orphan designation? How can gathering of HTA input very early in a medicine’s lifecycle with continuous follow up be facilitated? What if there are not sufficient slots available for early consultations? How can involvement of clinician and patient experts / integration of their views on key questions be improved? How will transparency of processes and decisions be implemented and tracked? How can divergence between countries in terms of expectations for EU HTA adoption (e.g., depending on national reimbursement system, use of HTA for patient access vs. for price negotiations, national economic models, etc.) be minimized? How can it be ensured that patient access to innovation is not hindered despite the divergence in expectation by different countries?