Experimental medicine challenge grants: discovery science in humans
Studies of disease mechanisms in humans
The Experimental Medicine Challenge Grants (EMCG) initiative supports ambitious programmes of research into disease pathophysiology, conducted in humans. The MRC seeks to generate new and deeper understanding of human disease mechanisms and identification of potential new therapeutic targets, so accelerating translation of basic science to impact on patient health.
These studies, addressing the biggest gaps in understanding the causes and progression of human disease, will produce major new mechanistic insights, with potential application to new therapeutic or diagnostic approaches and opportunities for 'reverse translation' to basic research.
This is the third round of this competition. View previous awards.
The deadline for outline applications is 25 June 2015.
Aims and remit
Applications should aim to produce major improvements in the understanding of human disease mechanisms, and must be:
- Challenge-led: Based around a substantial and clearly articulated gap in understanding of human pathophysiology
- Human-focused: The focus should be on understanding human disease through experimental investigation in humans. While projects may include a small element of non-human work (if informed by or informing the work in humans), the main focus of the project should be on human participants.
- Ambitious and innovative: Research proposals should address important medical questions in new ways.
- Experiment-driven: Proposals should be structured around an experiment designed to address a mechanistic question and identify clear outcomes.
Read about the role and value of Experimental Medicine (EM) in relation to other research approaches, and example case studies of previous awards.
Scale of awards
The EMCG scheme will support a range of award scales from smaller, focused, more exploratory and highly innovative projects (for example based on an intellectually sound hypothesis but perhaps lacking extensive pilot data), to large programmatic awards based on a more substantial platform of data.
The smaller exploratory awards will be reviewed as 'pathfinder awards', and it is anticipated that funding for pathfinder awards will be less than £1.2m per grant.
Prospective applicants are strongly encouraged to participate in the following opportunities:
At 11am on 8 May 2015, MRC will hold a webinar to articulate the remit and strategic intent of the EMCG scheme. Speakers will include Professor Stephen Holgate (chair of the EMCG panel), Professor David Lomas (MRC Board chair and EMCG panel member), Professor Steve Williams (EMCG co-PI) and Dr David Crosby (MRC programme manager for experimental medicine).
Participants will be able to watch the talks live online, and will be invited to submit questions for the speakers via email, which will be answered in real time. The panel will address the aims of the scheme, what qualifies good experimental medicine, challenges identified from previous rounds and how successful applications were designed, reviewed and conducted.
Go to the webinar page.
The email address for live webinar questions is: firstname.lastname@example.org.
EMCG regulatory and ethics workshops
There is often a perception that conducting experimental studies of disease mechanism in human subjects can entail significant regulatory and ethical complexity. This is surmountable, however, and there are ways to minimise the barriers to approval by planning and involving others where appropriate. In partnership with the MRC Regulatory Support Centre, we will hold two regional workshops (5 May in London and 6 May in Leeds) for prospective EMCG applicants, which will:
- Describe the regulatory and ethics landscape around EM work
- Highlight the resources and assistance available
- Provide practical suggestions on how to successfully navigate the pathway to regulatory and ethical approval
The workshops will involve presentations from university and NHS ethics committee members, HRA, and EMCG holders who will describe their experiences and strategies for getting EM studies up and running.
Applicants are strongly encouraged to attend one of these two workshops. Places at these workshops are limited, and available on a first-come, first-served basis. Please contact email@example.com for an agenda and to book a place.
Lead investigators should demonstrate a strong track record of relevant research, commensurate with the ambitious nature of these awards. Less established researchers are encouraged to apply for smaller pathfinder awards.
The following points are suggested as facets of good experimental medicine (EM) studies, and should form the core of proposals:
- Focus on the experiment
EM studies should be hypothesis defining/refining; EM is more than hypothesis-free characterisation, and is more exploratory than hypothesis-testing confirmatory work.
- EM is more than just data collection: emphasis on the experimental. Proposals may include:
- An experimental intervention/challenge in humans, perturbing the system to explore disease mechanism. Challenge may be pharmacological, immunological, physiological, psychological, infectious etc.
- The use of novel readouts or technologies
- The use of drugs, other interventions or measures with established safety profiles in new settings/conditions – e.g. repurposing drugs as tool compounds to probe disease mechanism
- Proposals may include, but should not solely focus on, deep characterisation/phenotyping of subjects. Proposals which are predominantly descriptive are unlikely to be shortlisted; an experimental approach, and a clear plan for establishing causal relationships and mechanisms, is expected.
Projects do not need to develop/test therapeutic interventions – developmental clinical projects are usually supported through MRC’s translational schemes – but exploratory studies with potential to both advance understanding of disease mechanism and also provide initial evidence for a potential treatment are welcomed.
- EM is more than just data collection: emphasis on the experimental. Proposals may include:
- Detailed plans
Full applications must include detailed experimental plans, comparable to requirements for a programme grant application. Lack of detail was a very common reason for rejection in previous funding rounds (Outline applications should have a defined plan for the experiments, with commensurate detail).
- Proposals need a structured rationale for the mechanistic hypothesis to be defined and tested, and for the readouts and measures which are proposed
- Studies should be methodologically and statistically rigorous in design and should take appropriate steps to minimise bias, and we recommend that applications include appropriate support (e.g. a statistical co-applicant) for this aspect.
- Novel approaches, imaging, integrative models and computational approaches are encouraged where appropriate.
Applicants are encouraged to explore collaboration with industry to facilitate the above experimental approach (however this is not mandatory). Opportunities exist through the MRC-Industry Asset Sharing initiative. There is also additional guidance for EMCG applications using the Asset Sharing initiative.
Partnership with charities is welcome, eg in access to established patient cohorts or use of infrastructure. Co-funding of proposals will be considered.
Collaborations between institutions, between scientific/clinical disciplines, with industry or with overseas expertise are encouraged but must add demonstrable value to the project, and include clear management plans. Partnerships may add value, for example, in terms of access to expertise, technologies, reagents, patient groups, data or funding. The MRC does not have the capacity to broker these arrangements.
Applicants should look, where appropriate, to make use of existing infrastructure for experimental medicine, e.g.:
- Scientific risk and adaptation
Projects that explore new areas will involve scientific risk that results are not as anticipated. For larger, longer-term programmes we expect to see risk mitigation plans addressing, for example:
- What alternate strategies will be employed if results at an early stage of the project are not as expected?
- What would need to be established before embarking on the higher-cost parts of the programme?
MRC is keen to provide researchers with committed support for longer term programmes, but may need to identify milestones and stage-gates – identified by the applicants in the proposal, or identified in review – along the pathway of the study.
Applications should be supported by relevant pilot data to provide confidence in the approaches proposed. Applicants developing higher-risk, smaller projects should consider the Pathfinder stream.
- What not to do
Recurrent issues with unsuccessful applications in previous rounds included:
- Excessively broad and all-inclusive ‘omics approaches, without sufficient rationale for the variables to be measured.
- Unnecessarily high costs resulting from lack of focus – applicants should consider “what is the critical path?”
- Under-powering and poor statistical consideration and study design, e.g. around effect size estimation.
- Weak case for the importance of the work in the context of other studies in the area, and the potential impact of the mechanistic knowledge that will be gained. How will the insight gained be exploitable or developed further in subsequent studies?
- A lack of innovation in the methods and measures employed (this may facilitate new avenues of investigation and new insight, but is not mandatory)
Who can apply?
Research council units and institutes (including intramural MRC units) can apply to this scheme.
Research proposals that are led by commercial entities are not eligible. Applications may, however, include collaborations with commercial parties under the MRC Industry Collaboration Agreement (MICA) framework.
Application process and deadlines
There is a two-stage application process – an outline application followed by a full application (where invited).
The deadline for outline applications is 25 June 2015, 4pm. Your proposal must be submitted through the RCUK Je-S system by 4pm on this date.
Outline applications should be submitted using the experimental medicine challenge grant outline form (DOCX, 71KB), which will be uploaded as the Case for Support, in addition to the CV and publications of the applicant and the summaries required by the Je-S system.
Full applications will be invited to submit to a deadline in October 2015, with decisions in February 2016. The full application form will be provided to successful applicants following the outline stage decision.
Please bear in mind that all proposals have to be submitted via your research organisation’s administrative department. Please ensure sufficient time to complete their parts of the proposal before the MRC deadline dates. Standard MRC terms and conditions will apply to this scheme.
In addition to standard MRC funding criteria:
- Question: Does the proposal address an important, clearly-articulated and tractable gap in understanding?
- Challenge: Is the challenge sufficiently ambitious and demanding to warrant funding through this scheme rather than research grant support?
- Strategy: Is an appropriate experimental scientific strategy presented to address the challenge? Have the investigators chosen a suitable range of approaches to deliver new insights, and do the individual strands of work reinforce each other? Do the initial phases of the work proposed give confidence in the project?
- Collaborations: Do any collaborations between disciplines, institutions or with industry add value to the project?
- Infrastructure: Is the required clinical infrastructure in place? Do the applicants plan to make use of BRC/Us, CRFs, patient cohorts or other established infrastructure?
- Experimental design and statistical considerations: Have the applicants described a clear experimental design with appropriate statistics for the conduct and analysis of the research? Are appropriate staff involved to support this?
Applications involving collaboration with industry should adhere to our Industry Collaboration Agreement (MICA) guidance. The lead applicant must be the academic partner, and we will meet the academic costs of the project only. MICA forms and Heads of Terms are not required at the outline application stage (only at full application stage), but letters of support confirming industrial partner engagement are required.
The terms of collaboration, particularly in relation to industry, should be determined early in the study development and relevant agreements must be in place by the outset of the project. Partnership arrangements should ensure transparency in the project design and in the analysis and publication of results (including if these are negative).
Consideration should also be given to issues such as: relative responsibilities, governance arrangements, regulatory approvals, indemnity, intellectual property rights, reporting, and access to data and samples.
Note that the generation of intellectual property is not a requirement for this scheme.
Intellectual property generated in the course of a project will (subject to the conditions of the MICA system) be owned by the host institution, which will have the right to manage and exploit this intellectual property.
The costs of managing, protecting and exploiting the intellectual property are borne by the host institution and are not eligible costs for MRC support.
Ethics and governance
We do not require ethics permissions and regulatory approvals to be in place when you submit an application.
However, given that research involving human subjects or requiring the use of human tissue/organs may raise various ethical and regulatory issues, applicants will be required to demonstrate that they have adequately considered these matters.
Early discussions with regulatory bodies are advised to ensure that all requirements can be met in a timely manner. Once an application is successful, it is the responsibility of the host institution to ensure that the appropriate ethics and regulatory approval has been obtained and that no research requiring such approval is initiated before it has been granted.
Please read our terms and conditions for further details.
Proposals are funded on the basis of 80% of the full economic cost (except for 'exceptional costs', which are funded at 100% - see the guidance for applicants (PDF, 830KB)). The MRC will meet the academic costs of the project only.
Applicants should refer to the AcoRD guidance to ensure that research costs, NHS treatment costs and NHS support costs are correctly attributed.
*This guidance is applicable to England, Wales, Scotland and Northern Ireland.
You are encouraged to discuss your proposal with the MRC Programme Manager for Experimental Medicine, Dr David Crosby, before submission:
Tel: 0207 395 2215