Demand management
Demand management is being applied to this funding opportunity. Further details are provided in the ‘Who can apply’ section.
Scope
As the UK population grows and ages, increasing rates of ill health and declining healthy life expectancy are contributing to a worrying trajectory for health outcomes. The shift to prevention from treatment as part of the 10-year NHS health plan for England has the potential to reduce the burden of multiple long-term conditions and chronic diseases, support an ageing population, tackle health inequalities, lower associated NHS costs, boost productivity and drive economic growth.
Some effective prevention interventions already exist, but their impact is often limited by substantial variation in how individuals and populations respond. Heterogeneity is commonly observed in response, risk reduction, adverse effects, and clinical outcomes associated with biomedical interventions. The biological mechanistic pathways underpinning this variation are poorly understood.
Current approaches typically rely on average effects across diverse populations, leading to suboptimal benefit, unnecessary treatment, and persistent health inequalities. This funding opportunity aims to support interventional studies in humans to validate a mechanistic hypothesis and directly interrogate the biological mechanisms governing the transition from health to early disease and the mechanisms underlying variation in response to biomedical prevention interventions.
By deploying experimental challenges, interventions or controlled perturbations, studies can test biological mechanisms, with measurable outcomes providing evidence of the pathways involved, rather than inferring them from observational data. These mechanistic insights then inform how prevention interventions could be better targeted, timed, and delivered across different populations. These findings should contribute to an iterative feedback loop of mechanistic insight and re-testing that enables progressively more precise and effective prevention strategies.
Studies may address the heterogeneity of response of existing validated prevention interventions or investigate biological mechanisms that could support the future development of novel precision prevention interventions. In all cases, relevant, validated biological readouts must be measured to test the proposed mechanistic hypothesis. Exploratory biomarker studies are not eligible for funding.
Successful projects should address a clearly articulated gap in understanding the mechanisms underlying variation in response to preventive interventions or the biological mechanisms governing the transition from health to early disease. This should have a clear pathway to informing the targeting, timing, or optimisation of precision prevention approaches. Projects should demonstrate how these insights could enhance the effectiveness, efficiency, and equity of prevention, including by identifying opportunities to tailor interventions to those (high risk) people and populations most likely to benefit.
Project themes could include a combination of the following (non-exhaustive):
- improving mechanistic understanding of how interventions modify biological pathways across different population groups, enabling more personalised and equitable prevention approaches and avoiding harm
- generating mechanistic insights into early disease pathways that can enable the future development and tailoring of novel precision prevention approaches and support the stratification of populations
- use of current treatment interventions as mechanistic tools to understand pathways that influence responsiveness to prevention interventions and inform stratified prevention approaches
- validating surrogate endpoints that reflect biological mechanisms underlying heterogeneity in response to prevention interventions and track the transition between health and disease. This should not be the primary focus of the application
What your application must include
Your application must involve an experimental investigation in humans at its core, which has been designed to validate a mechanistic hypothesis. Projects must focus on the pre-disease state, early stage or emergence of disease. This should include a biomedical intervention or challenge, with an established safety profile, such as pharmacological or immunological.
We particularly welcome applications that address gaps in our understanding of biological mechanisms in multiple long-term conditions and metabolic disease and, where relevant, in underrepresented populations.
Activities we do not support
The activities that are ineligible for support are:
- characterisation or phenotyping work aiming to elucidate disease aetiology, where this is the main aim and without an experimental challenge or prevention intervention context
- experimental intervention or challenge in animals, using clinical assets to explore prevention and disease mechanisms and pathways
- biomarker discovery projects
- projects where the primary mechanistic question is directed at managing established disease rather than preventing its onset (tertiary prevention)
- pre-clinical model development and validation
These activities are supported through the following Medical Research Council (MRC) applicant-led funding opportunities:
The following activities are also ineligible for support through this funding opportunity:
Learn about MRC’s remit, programmes and priority areas.
Please see the ‘Additional information’ section for a video on this funding opportunity and answers to frequently asked questions.
Duration
The duration of this award can be between three and five years.
Milestones
Milestones allow us to mitigate risk and support potentially high-risk, innovative projects.
Experimental medicine awards will typically have at least two milestones with defined success criteria that reflect timely progression points and allow mechanistic hypotheses to be laid out and assessed as the project moves forward.
As part of the invited full application stage, your milestones should also provide a realistic indication of timelines for key steps, such as regulatory steps, study team recruitment, participant recruitment, study completion and data analysis.
Milestone success criteria should be SMART (specific, measurable, achievable, relevant and timely) and detail any robust go or no-go criteria. For all projects, it is advisable to structure the project so that the critical questions are addressed as early as possible in the plan.
Funding available
The total budget for this funding opportunity is £15 million.
The FEC of your project can be up to £5 million.
MRC will fund 80% of the FEC and 100% of permitted exceptions.
Find out more about full economic costing.
What we will fund
You can request funding for costs such as:
- a contribution to the salary of the project lead and co-leads
- support for other posts such as research and technical staff
- research consumables
- equipment
- travel costs
- data preservation, data sharing and dissemination costs
- estates and indirect costs
- public partnerships and related activities, including payments to public contributors
You can also request costs for work to be undertaken at international organisations by international project co-leads. We will fund 100% of the eligible costs.
The total of such costs requested for international applicants from high income countries (those not on the OECD DAC list of ODA recipients), India and China, must not exceed 30% of the total resources requested.
There is no cap on costs requested for international applicants from development assistance countries (DAC).
For more information on international costs and what we will and will not fund see costs we fund and the Collaborate with Researchers in Norway guidance.
What we will not fund
We will not fund:
- clinical studies designed to assess the safety or efficacy of treatments
- costs for PhD studentships
- publication costs
- funding to use as a ‘bridge’ between grants
Supporting skills and talent
We encourage you to follow the principles of the Concordat to Support the Career Development of Researchers and the Technician Commitment.
Trusted Research and Innovation (TR&I)
UK Research and Innovation (UKRI) is committed in ensuring that effective international collaboration in research and innovation takes place with integrity and within strong ethical frameworks. Trusted Research and Innovation (TR&I) is a UKRI work programme designed to help protect all those working in our thriving and collaborative international sector by enabling partnerships to be as open as possible, and as secure as necessary. Our TR&I Principles set out UKRI’s expectations of organisations funded by UKRI in relation to due diligence for international collaboration.
As such, applicants for UKRI funding may be asked to demonstrate how their proposed projects will comply with our approach and expectation towards TR&I, identifying potential risks and the relevant controls you will put in place to help proportionately reduce these risks.
See further guidance and information about TR&I, including where applicants can find additional support.
