Rationale
Dementia describes a collection of typically progressive symptoms associated with damage to the brain caused by diseases, such as Alzheimer’s disease, Lewy body dementia, vascular dementia, fronto-temporal dementia and others. The prevalence and therefore burden of dementia is set to increase, from an estimated 885,000 people currently living in the UK with dementia to 1.3 million by 2040. In recognition of this, the UK government has identified dementia as a key healthcare challenge for the future in a number of priority-setting documents, including the Life Sciences Vision and recently announced 10-Year Plan for Dementia.
There is a rich research and development ecosystem already seeking to address this challenge, including pharmaceutical companies and collaboratives, charities, centres of expertise such as the UK Dementia Research Institute and research infrastructure such as the Dementia Platform UK.
While there has been significant scientific progress in recent years, which may support a growing pipeline of interventions, there remains a need for translational research to evaluate potential new treatments, and it is important that future investment focusses on addressing bottlenecks for progress. As articulated in the Life Sciences Vision, the development of novel precision treatments and application of biomarker discoveries is particularly challenging, but key to supporting a pipeline of interventions which target a range of mechanisms.
It was demonstrated in the recent 10-year impact assessment that the EME programme is uniquely positioned to support the translation of discovery science by funding clinical trials which support the testing of promising interventions, with embedded research to further understand their mechanisms of action. EME is able to support the evaluation of precision medicine technologies, as well as the definitive evaluation of markers to predict treatment response and thereby inform clinical decisions.
For this call, the EME programme will also support opportunities within the study to validate biomarker-based endpoints for use in clinical efficacy trials. Any such elements must build on clinical evidence of the marker’s potential and may not be exploratory. Applicants should clearly demonstrate the ability of the study design to validate these biomarkers, which must not be at the expense of the efficiency of the efficacy study.
Through this call, the EME programme hopes to commission a platform study to efficiently address current knowledge gaps and elevate translational clinical trial activity in dementia. The platform will support definitive efficacy trials of novel and repurposed interventions, with the opportunity to also support research into the clinical application and evaluation of biomarkers.
The platform must be clearly positioned to complement significant investments in earlier-phase clinical and biomarker validation research, by collaborating with existing infrastructure and seeking to build on any proof of concept established through these initiatives.
Call scope
The aim of this call is to commission a single adaptive platform study with the following objectives:
- Primary Objective: To evaluate the efficacy of potential interventions in dementia, particularly those trialling a precision medicine approach. The platform could focus on one main subtype of dementia, or include several.
- Opportunity to include: Where defined and justified by applicants, other objectives may include the evaluation of biomarkers for patient stratification, predictive markers of treatment response and validation of biological measures of clinical efficacy, within clinical trials.
All components of the study should be within remit of the EME Programme. Specifically:
- Interventions must be fully developed with sufficient human proof of concept that the intervention may be of benefit (i.e. a signal of efficacy in dementia or findings which may be considered transferrable, with a sound mechanistic rationale) to justify the proposed trial.
- Biomarker components must build on early stages (discovery, accuracy studies, technical validation and early clinical validation) and aim to evaluate the clinical and/or research utility of markers; they must test a well-defined hypothesis and must not be hypothesis-generating.
At the outset, applications must define a body of work, including the interventions and any biomarker research to be conducted. As an adaptive study, the platform should have the flexibility to incorporate additional interventions as promising candidates are identified. Applicants may also wish to consider how to incorporate or support additional biomarker work throughout the project.
It is therefore anticipated that commissioning in this important area will comprise two stages:
- Part 1 – MRC-NIHR EME Programme call to commission the infrastructure of a platform trial, including initial interventions and biomarker components.
- Part 2 – Additional funding to support per-intervention costing, to continue to populate the platform. Applications should describe an Independent Scientific Advisory Group to oversee the identification and prioiritisation of candidates.
Applications must link with the relevant clinical trial infrastructure across the dementia research landscape, particularly with regards to recruitment centres and the prioritisation of further candidate interventions.
Out of scope
The EME Programme is not able to fund biomarker discovery research or evaluate biomarkers of disease progression. For earlier stage biomarker research, teams may wish to refer to MRC funding opportunities. In particular, for biomarker validation and translational clinical studies which constitute proof of concept in humans, applicants may wish to refer to the MRC Developmental Pathway Funding Scheme (DPFS).
Applications to clinically validate novel diagnostic tests, while within remit of the programme, are not included within the scope of this call and may instead refer to EME Researcher-Led funding opportunities.
Although the EME programme may not directly fund these elements, any study funded from this call is strongly encouraged to support, through sample discoverability, availability and data sharing, other important biomarker work in dementia.
Duration and costs
EME is keen to receive applications to this call for a large and ambitious study. There is no set upper limit for the duration or cost of applications, however value for money will be a key consideration.
Applications must detail project costs and duration according to the initial interventions and biomarker components proposed.
As further potential therapies and/or applied biomarker sub-studies are prioritised by the Independent Scientific Advisory Group, details including additional costs will be submitted to the NIHR for consideration. Amended payment schedules will then be agreed for any further funding.
Applicants are encouraged to consider the sustainability and growth of the platform beyond the initially funded work, where relevant.
Process for Assessment of Applications
Applications to this call will follow a two-stage application process.
The deadline for Stage 1 applications will be: 4 May, 2023
The deadline for shortlisted Stage 2 applications will be: 7 September, 2023