MRC Experimental Medicine Grants Stage Two: How to Win Major Funding for Human Intervention Studies

If you work in experimental medicine and you have just been invited to stage two, you are standing at the serious end of the pool. This is where ideas stop being hypothetical and start being costed, scheduled, and judged against the best in the field.

The Medical Research Council (MRC) Experimental Medicine scheme is one of the UK’s flagship routes for funding intervention studies in humans. It is designed for projects that do more than observe disease – they deliberately intervene, perturb, challenge, and then watch what happens at the mechanistic level.

The opportunity is unusual in a very good way: there is no set upper limit on the budget and no fixed maximum project length. In research council terms, that is about as close to “design what you really need” as you will ever get.

However, this article is not for everyone. This is specifically about the invited stage two application. That means:

• You (or your institution) already submitted an outline or stage one application.
• Reviewers liked it enough not to bin it.
• You have been invited to submit a full proposal.

Now comes the hard part. Stage one is about plausibility. Stage two is about proof: can you plan and deliver a sophisticated mechanistic human study, safely, ethically, and with a coherent budget that makes sense?

Below is a practical guide to turning that invitation into a fully funded award.

Experimental Medicine Stage Two at a Glance

What This Experimental Medicine Grant Actually Offers

This opportunity is built for researchers who want to test mechanistic hypotheses in humans using real interventions, not just questionnaires and retrospective datasets.

At its core, the scheme pays for the full machinery of a human experimental medicine study: developing or repurposing interventions, recruiting patients or healthy volunteers, delivering the challenge or perturbation, collecting complex data, and analysing what that intervention tells you about disease mechanisms.

Because the MRC pays 80% of the full economic cost, you’re not just asking for salary and consumables. You are building a package that includes staff time, overheads, facility charges, and everything your institution normally loads onto research budgets. There is no official cap, which is rare and powerful – but it also means reviewers are hypersensitive to whether you are asking for the right amount, not just “as much as you can get away with”.

The absence of a max project length gives you room to design a study that follows participants long enough to answer real mechanistic questions. For example, you might propose:

• A 5-year longitudinal intervention trial exploring immune signatures after biologic therapy.
• An 18-month challenge study in healthy volunteers evaluating response to a viral, metabolic, or pharmacological challenge.
• A 3-year mechanistic sub-study nested within an existing clinical trial, with deep phenotyping and molecular readouts.

The scheme is also explicitly welcoming to new investigators. If you’re taking the leap from being “someone else’s postdoc” to a fully independent PI, this can be the grant that shifts your CV from promising to proven. It’s not a starter grant in the sense of size or ambition; instead, it’s a chance to prove you can lead a complex human study with the right mentorship and support.

Because this is an ongoing funding opportunity, not a one-off call, the scheme runs multiple decision points. But your particular stage two deadline is locked: 11 March 2026, 16:00. Miss that, and your lovingly crafted full proposal will simply not be considered.

Who Should Apply (and Who Should Not)

To be blunt: if you have not been explicitly invited to stage two, close this tab and go back to stage one or to other schemes. Stage two is not open to new applicants; it is the second act for those whose outlines already impressed the panel.

Assuming you have an invitation, you’re in the right place if:

• You are based at an eligible research organisation – typically a UK university, NHS trust, or approved independent research institution with the infrastructure to run human studies.
• Your project has a clear mechanistic hypothesis. That means you’re not just asking “does this treatment work?” but “how, in biological or physiological terms, does this intervention change the system?”
• Your study includes a direct intervention or challenge in humans – a drug, device, behavioural challenge, immunological stimulus, dietary manipulation, controlled infection, or similar. Purely observational cohort work will not cut it here.
• You are ready to manage ethics, governance, and trial logistics. Even if this is not a full-scale clinical trial, you are still intervening in humans; that brings layers of oversight, paperwork, and risk management.
• You (or your team) have, or can credibly access, the technical expertise to measure the mechanistic outcomes you care about – cellular readouts, imaging, -omics, physiological measures, whatever your hypothesis demands.

This scheme is particularly good for:

• Translational scientists wanting to take strong preclinical mechanistic work into humans.
• Clinician-scientists who see interesting phenomena at the bedside and want to test mechanistic hypotheses in patients.
• Interdisciplinary teams combining, say, immunology and neuroimaging, or computational biology with intensive human phenotyping.
• New investigators who have built a coherent research niche and can show institutional support and mentorship.

It’s a poor fit if:

• Your work is purely preclinical or animal-based without a human intervention.
• You’re mainly interested in service evaluation, audit, or routine outcome assessment.
• You just want to run a big pragmatic clinical trial to test effectiveness without deep mechanistic readouts – that’s more for NIHR or other trial-focused schemes.

Insider Tips for a Winning Stage Two Application

Stage two is about detail. Reviewers already liked your idea; now they want to know exactly how you’ll deliver it. Here is where successful applicants consistently pull ahead.

1. Make the Mechanistic Hypothesis Crystal Clear

Every single part of your proposal should orbit one clear mechanistic hypothesis.

Instead of “we want to see what happens to inflammation after drug X,” you want something like:

“We hypothesise that blocking receptor Y with drug X reduces synovial inflammation by disrupting Z-signalling in macrophages, leading to a specific change in cytokine profile A and imaging marker B.”

Then show how each experiment, each readout, each timepoint is designed to test that hypothesis. If you have multiple hypotheses, rank them: primary, then secondary. Scattershot curiosity reads as unfocused.

2. Draw a Straight Line from Intervention to Readout

Reviewers hate vague connections. For every key mechanistic endpoint, explain:

• Why this readout is the right way to see the mechanism in action.
• Why the timing of measurements makes sense relative to the intervention.
• How big a change you expect and why that’s realistic.

A simple diagram linking intervention → immediate biological impact → downstream measurable outcome can massively help reviewers who are not deep specialists in your precise niche.

3. Treat Safety and Ethics as Central, Not an Afterthought

You are intervening in humans. Even relatively benign challenges (e.g. dietary restriction, exercise stress tests, immune stimulation) need careful justification and monitoring.

Spell out:

• Inclusion and exclusion criteria and why you chose them.
• Monitoring plans and stopping rules.
• Management of adverse events, especially for higher-risk interventions.
• How you will explain risks and benefits to participants in plain language.

If reviewers sense hand-waving around safety, they will mark you down fast.

4. Build a Budget That Matches the Story

Because there is no fixed cap, some people overshoot wildly; others under-cost and look naive. Both are risky.

Work from the bottom up:

• Calculate realistic recruitment costs (staff time, advertising, clinic slots).
• Cost specialist assays properly (reagents, platform charges, data analysis).
• Do not forget data management, statistical support, and trial coordination.
• Use institutional templates for FEC so your 80% MRC request is accurate.

Then write a budget justification that reads like a narrative: “To deliver X participants through Y visits with Z complex assays, we require…”. Make it clear that cuts to key items would damage the science.

5. Prove You Can Deliver the Recruitment

Many excellent mechanistic ideas die on the rock of over-optimistic recruitment.

Show that you understand:

• The size and characteristics of the population you’re targeting.
• Realistic recruitment rates given clinic flow, inclusion criteria, and competing studies.
• How you will keep people in the study (reasonable visit schedule, reimbursement, flexible appointment times).

If you’re using healthy volunteers, describe your recruitment channels and past experience. If you’re using rare disease populations, explain how you’ll reach them and what happens if recruitment is slower than hoped.

6. Nail the Team Story

MRC panels want to know: is this the right team, in the right place, with the right support?

Explain:

• Each investigator’s role and why they are essential.
• How senior and junior staff will work together (especially important for new investigators).
• Access to specialist facilities (CRFs, imaging, GMP units, -omics platforms, biobanks).

Letters of support should be specific and operational, not just “X is brilliant”.

7. Write for Smart People Outside Your Niche

Your reviewers are experts, but not necessarily in your exact disease or method. Draft your proposal so that a good clinician or scientist in another field can still follow the logic.

Avoid drowning them in acronyms and minutiae. They need to see the big picture clearly enough to argue for you in the panel room.

Building a Realistic Application Timeline

Working backward from 11 March 2026, 16:00, here’s a sensible schedule. If you’re closer than six months to the deadline, compress carefully, but don’t skip steps.

• September–October 2025: Strategy and Structure
  Revisit the stage one feedback, even if it was glowing. Clarify your main hypothesis and refine the study design. Draft a 1–2 page “concept plus aims” document and circulate it to your core team for brutally honest comments.

• November–December 2025: Full Drafting
  Write a complete draft of the scientific case, methods, and workplan, even if rough. At the same time, begin your conversation with the trials unit, CRF, or clinical governance teams who will support recruitment and delivery.

• January 2026: Refine the Science and Stats
  Lock down your sample size calculation, outcome measures, and analysis plan. This is often where statisticians identify issues that need tweaks to design or recruitment. Better now than in review.

• Late January–February 2026: Costing, Approvals, and Internal Sign-off
  Work with your research office to build the FEC budget and check institutional deadlines. Many universities require internal sign-off days or weeks before the MRC deadline. Align on this early.

• Mid–Late February 2026: External Reviews
  Send the near-final version to 2–3 colleagues who are not on your project. Ask them specifically: “Where would you attack this if you were a reviewer?” Incorporate their feedback ruthlessly.

• First Week of March 2026: Final Polish and Submission
  Aim to submit at least 48 hours before the deadline. Check every attachment, every section, every figure. Confirm everyone’s details in the UKRI Funding Service are correct. Technical problems at 15:40 on 11 March will not earn you sympathy.

Required Materials and How to Prepare Them

The exact online form fields will be in the UKRI Funding Service, but you can expect to prepare, at minimum:

• Case for Support / Project Description
  This is the heart of your bid. It should lay out the background, mechanistic hypothesis, study design, intervention, outcomes, analysis plan, and timeline. Use diagrams to make complex designs digestible.

• Justification of Resources
  Go beyond “we need a research nurse”. Explain why each staff member, piece of equipment, and consumable category is essential to deliver the mechanistic aims.

• CVs and Track Records
  These should be tailored, highlighting experience with human studies, previous grants, relevant publications, and any prior work that led to this specific proposal.

• Letters/Statements of Support
  From host institutions, clinical sites, platform facilities, and collaborators. They should confirm access, contribution, and any in-kind support (clinic time, imaging slots, data infrastructure).

• Ethical and Regulatory Considerations
  A clear plan for ethics approval, trial registration if needed, MHRA engagement for IMPs or devices, and any data protection issues (especially if using high-dimensional or genetic data).

• Data Management and Sharing Plan
  Describe how you will store, curate, and share datasets safely and meaningfully. Panels increasingly expect genuine thought here, not placeholder sentences.

Get templates and examples from your research office or colleagues who have won MRC experimental medicine grants. You do not need to reinvent the format; you need to sharpen the content.

What Makes an Application Stand Out to Reviewers

Panels assessing experimental medicine grants typically weigh several broad themes.

1. Scientific Rigor and Mechanistic Clarity

The best applications make it blindingly obvious:

• What question they are asking.
• Why this is the right question at this stage of knowledge.
• How the intervention will test the hypothesis in humans.

Reviewers should leave thinking, “If this is done as described, we will genuinely understand something new about disease mechanisms.”

2. Feasibility in the Real World

MRC panels are populated by people who know exactly how hard human studies really are. They will interrogate:

• Recruitment assumptions.
• Complexity of the protocol.
• Capacity of the sites and facilities.
• Experience of the team with similar work.

A slightly less ambitious but clearly feasible project often scores better than an overblown one that feels heroic but implausible.

3. Quality of the Team and Environment

Strong applications show a coherent team: clinical expertise, mechanistic science, statistics, trial management, and data analysis are all visibly present.

Competitive bids also highlight institutional strengths: existing cohorts, embedded clinical research facilities, strong governance systems, and supportive leadership.

4. Potential for Long-Term Impact

Even though the immediate aim is mechanistic, reviewers also think downstream:

• Could this work redirect a drug development programme?
• Might it reshape how we classify patients or predict response?
• Does it open up new therapeutic strategies or repurpose existing ones?

You are not promising a cure by the end of the grant, but you should show a plausible pathway from mechanism to future patient benefit.

Common Mistakes to Avoid (and How to Fix Them)

1. A Vague or Overstuffed Hypothesis

Trying to answer five big questions in one study usually means answering none of them well.

Fix: Strip down to the core mechanistic question and 1–2 tightly linked secondary questions. Anything else goes in the “future work” section of your head.

2. Over-Optimistic Recruitment

“Recruit 300 patients with a rare subtype over 18 months from a single centre” is the sort of line that makes panels wince.

Fix: Base projections on actual clinic throughput, previous studies, or registries. If needed, extend recruitment time or add sites.

3. Underpowered Mechanistic Endpoints

It’s not enough to say you’ll measure fancy biomarkers; you need an analysis plan that can actually detect meaningful differences.

Fix: Work closely with a statistician on power calculations, even for mechanistic outcomes. Justify sample sizes explicitly, not just with hand-waving.

4. Thin Safety and Governance Planning

If harms, oversight, and contingency planning are only glanced at in the final paragraph, reviewers will assume you haven’t thought deeply about them.

Fix: Integrate safety into the design section. Detail monitoring, stopping rules, oversight committees if appropriate, and plans for handling protocol deviations.

5. A Budget that Looks Made Up

Asking for a suspiciously round number with no clear mapping to activities raises eyebrows.

Fix: Build your budget from activity-based costing and use the justification section to show the logic connecting cost to deliverables.

Frequently Asked Questions

Do I really need a human intervention or challenge?
Yes. This scheme is explicitly for experimental medicine studies where you do something to participants – give a drug, impose a challenge, adjust a behaviour – and study the mechanistic consequences. Observational or purely correlational studies belong elsewhere.

Can early-career or new investigators lead a stage two application?
Yes, if your institution and MRC consider you eligible as a “new investigator”. You’ll need to demonstrate clear independence, a distinct research vision, and strong mentorship and institutional backing. Panels can be very supportive of new investigators with convincing support structures.

Is there any upper limit to the funding request?
There is no stated cap, but “no limit” is not an invitation to inflate costs. Extremely high-cost proposals come under intense scrutiny, and you must show that every major item is essential to answer the mechanistic question.

Can I include international collaborators?
Typically, the host organisation receiving MRC funds must be eligible (usually UK-based). International collaborators can participate and may have some costs covered if justified, but the core grant will be anchored in a UK research organisation. Check specific UKRI guidance or email [email protected] for nuance.

What if my project needs more time than a standard 3-year grant?
Longer projects are possible, but they must be justified convincingly – for instance, if your mechanistic outcomes require long-term follow-up or complex staged interventions. Reviewers will ask whether all years are genuinely needed or whether the work could be structured more efficiently.

Is this the same as funding a full clinical trial?
Not necessarily. Some projects will sit within or alongside a trial, but the scheme’s focus is on mechanism, not just outcomes. A massive superiority trial powered purely on clinical endpoints but light on mechanistic content is better suited to other funders.

How do I get help with the application system or technical issues?
For content questions, email the MRC team at [email protected]. For issues with the UKRI Funding Service platform, use [email protected]. Do this well before the deadline; nobody can save a stuck submission at 15:59.

How to Apply and Next Steps

You cannot start at stage two; you must have an official stage two invitation from MRC. If you have that, your next moves are straightforward but require discipline.

1. Read the official guidance carefully.
   Go to the opportunity page and download or read every section on eligibility, assessment criteria, and required sections:
   Official page: https://www.ukri.org/opportunity/experimental-medicine-invited-stage-two-application/

2. Confirm internal institutional deadlines.
   Your university or NHS trust will likely have an internal review and sign-off process that sits ahead of 11 March 2026. Talk to your research office now so you don’t miss a hidden earlier cut-off.

3. Assemble your core team.
   Lock in your co-investigators, statistician, trial manager, and facility leads. Agree on responsibilities and timelines for their input. An experimental medicine grant is a team sport.

4. Draft the heart of the proposal first.
   Start with your mechanistic hypothesis, objectives, and study schema. Once these are sharp and agreed by the team, move to the more detailed sections and the budget.

5. Engage with MRC if you have grey areas.
   If you’re unsure whether your project fits the experimental medicine remit or how to pitch certain aspects, reach out early to [email protected]. They will not write your grant, but they can clarify expectations.

6. Build in review time.
   Plan for at least two full rounds of external feedback, ideally from someone who has previously sat on an MRC panel or held a similar grant.

When you are ready to move from ideas to submission, head to the official call:

Ready to submit your stage two proposal? Visit the official opportunity page for full details and access to the application system:
Experimental medicine invited stage two application – UKRI

Treat this stage two invitation as what it is: a serious vote of confidence in your idea. Now your job is to show MRC that you have the design, the team, and the realism to turn that idea into a rigorous, safe, and genuinely informative human study.