On The Edge Of HTA: Shaping the boundaries across borders and stakeholders to prepare HTA for future complex medicines

This thesis aimed to investigate how to prepare health technology assessment (HTA) organisations for the assessment of future complex medicines for reimbursement. The first part of the thesis studied the current challenges for HTA and discovered that these mostly stem from unavailable data. HTA assessors were positive towards using patient registry real-world data (RWD) in the case of complex medicines. However, many hurdles remain. For example, a discrepancy was seen between methods for comparing single-arm trials with RWD-based comparators in the literature and those used in practice. Tumour-agnostic therapies challenged current approaches to defining eligible patients and evidence generation. Variations in accepting uncertainties led to differences in adopting the agnostic indication across decision-makers. The second part focused on the current status of alignment between regulatory reviews, HTA reports and clinical guidelines (CGs). For multiple sclerosis medicines, variations were observed in the recommended treatment lines and sub-indications. Time lags exist between HTA report publication and clinical guideline uptake. Descriptions of recommended patient populations for oncology medicines evolved heavily throughout the lifecycle, highlighting the complexity of evidence-based decision-making for eligible patients. The third part investigated ways to improve alignment among regulatory authorities, HTA organisations, and CG developers. Focus group discussions revealed that alignment might be achieved through similar definitions and methods, and ‘multi-stakeholder dialogues’ to set evidence requirements followed by ‘joint parallel scientific consultations’. Additionally, guidance was developed which can be used to manage uncertainty throughout the drug development and evaluation process. In conclusion, this thesis underscores the need for HTA to adapt to the evolving healthcare landscape to prepare for future complex medicines.