BACKGROUND: The reimbursement landscape of available AD drugs is heterogeneous across countries, and challenges are associated with reimbursement decision-making. With several new agents currently in phase III clinical development, there is a need to understand HTA and payer evidence requirements in this disease area.

OBJECTIVES: To provide recommendations for HTA requirements in AD from a market access and health economics perspective based on previous assessments by HAS, IQWiG, and NICE.

METHODS: We searched the websites of HAS, IQWiG and NICE for assessments of currently available AD treatments. Then we mapped the identified requirements from the HTA reports with endpoints used in clinical trials of emerging therapies (identified through clinicaltrials.gov), namely aducanumab, donanemab, gantenerumab, and lecanemab. These interventions were included in our evaluation as they may be considered for future marketing authorisation.

RESULTS: Out of 31 HTA reports identified, we included only the most recent assessments (n=11) as these represent the current reimbursement landscape. From clinicaltrials.gov, we included 18 phase III clinical trials.

Donepezil, galantamine, rivastigmine, and memantine are reimbursed in Germany, England, and Wales but not in France. Cognition, daily function, behaviour, global clinical assessment, time to institutionalisation, mortality, adverse events, HRQoL, and caregiver burden were the most common endpoints used for decision-making across HTAs. However, for institutionalisation, caregiver burden, and HRQoL, the evidence provided in the submissions was deemed inadequate. Moreover, a common critique across HTAs was small evaluable sample sizes and a lack of long-term data.

The primary endpoints of the identified clinical trials were cognition, disease-specific functioning scales, and safety. None of the assessed trials included endpoints on HRQoL, caregiver burden, or institutionalisation.

CONCLUSIONS: Although clinical trials on new AD agents include HTA- and payer-relevant endpoints, it is highly recommended to also assess time to institutionalisation, HRQoL, and caregiver burden to generate a compelling HTA and payer evidence package.