Disease-modifying dementia treatments (DMDTs) target amyloid beta or tau proteins and have the potential to change disease progression, representing a step change in the management and treatment of Alzheimer’s disease. Given the novel mechanism of action and impact on health care, the NICE Health Technology Assessment Innovation Laboratory (HTA Lab) sought to identify and contextualize the key issues for future appraisals.

We reviewed published assessment reports of DMDTs from international HTA agencies and conducted a scoping review of published economic models of pharmacological treatments to understand the challenges associated with evaluating the cost-effectiveness of dementia treatments. The HTA Lab held an engagement workshop with 27 external stakeholders, including expert clinicians, implementation partners, health economists, and representatives from international agencies to discuss and confirm the key issues and considerations likely to emerge during an appraisal of DMDTs.

Key clinical and cost-effectiveness issues were identified and discussed. We concluded that consideration needs to be given to the diagnostic methods to identify the DMDT-eligible population in the UK, the validity of the surrogate outcomes used in the DMDT clinical trials, treatment effectiveness in different populations, and the incidence of DMDT-associated adverse events. Economic considerations include the type of economic model used in the appraisal, modeling the natural history of the disease, paucity of quality-of-life data in the treatment population, the inclusion of societal impact, treatment duration, stopping rules, and long-term effectiveness beyond the clinical trials.

DMDTs could have the potential to transform Alzheimer’s disease care. With multiple treatments on the horizon, the appropriateness and acceptability of the new mechanism of action underpinning these treatments should be considered. We have identified areas of uncertainty that are likely to arise during an appraisal process, to facilitate the timely approval of these medicines and patient access.

There are many challenges encountered in the health technology assessment (HTA) of treatments for the management of neurodegenerative diseases like Alzheimer’s disease. A recent example where such challenges were visible was the assessment of aducanumab, a medication developed for Alzheimer’s disease. As part of the Innovative Medicines Initiative (IMI) Neuronet project, a series of workshops were held to understand the gaps in neurodegenerative disease research and identify the key research priorities, from the perspective of different stakeholders, that can inform decision-making and enable timely access to effective and safe treatments.

Three workshops were organised by Neuronet to consult with HTA and regulatory experts, people with dementia and their supporters, and academic and industry researchers. The first consultation was with the European Working Group of People with Dementia and their supporters, and their feedback was fed into the following two workshops which were conducted with HTA and regulatory experts, and with researchers. Discussions during the workshops were used to develop a summary of the gaps in research, and priorities from the perspective of each stakeholder group to be submitted to IMI to inform future research funding allocation.

Key priorities that were highlighted from an HTA and regulatory perspective were the collection of longitudinal data to understand the natural history of the disease, the generation of data on long-term clinical outcomes and the use of trial endpoints that are relevant to clinical practice. There is also a need for disease-modifying treatments that is yet to be met in this disease area. Furthermore, the involvement of the public, particularly people with dementia and relevant organisations, in setting research priorities and informing study designs was highlighted as a priority by all stakeholders.

There are key priorities for future neurodegenerative research from an HTA and regulatory perspective to address current gaps and challenges. It is important to involve different stakeholders in priority setting and decision-making to produce relevant and satisfactory research outputs.