Medical Research Council - Developmental pathway funding scheme

Developmental Pathway Funding Scheme/Developmental Clinical Studies

Therapeutics, Devices and Diagnostics Development

The Developmental Pathway Funding Scheme/Developmental Clinical Studies scheme (DPFS/DCS) supports the translation of fundamental discoveries toward benefits to human health. It funds the pre-clinical development and early clinical testing of novel therapeutics, devices and diagnostics, including “repurposing” of existing therapies.

The DPFS/DCS scheme combines the previous individual translational funding schemes, permitting a more flexible and integrated approach to the development of new interventions and diagnostics. This scheme forms part of the MRC’s Translational Research Strategy and will be used to deliver the Biomedical Catalyst in the short term. Academic-led applicants should refer to the existing guidance and forms for DPFS/DCS; where the proposal involves collaboration with one or more industrial partners the applicant will need to submit a MICA form and Heads of Terms, at the full stage, if invited forward

Remit
Funding available
Eligibility
Collaborations
Costs
Application process
Oversight
Intellectual property
How to apply and timings
Ethics and governance
Additional guidance
Publishing results
Panel membership
Contact

Remit

The DPFS/DCS scheme will support projects targeting significant health needs by improving prevention, diagnosis, prognosis, or treatment of disease, or by developing research tools that increase the efficiency of the development of interventions.

Projects supported by the scheme will have clearly defined milestones, outcomes and future plans. These will help to maximise success and enable the project to attract required downstream funding, whether from public or private sources, along the path to meet its clinical aims. The DPFS/DCS Panel will, if necessary, help to develop proposals and suggest enhancements.

The DPFS/DCS scheme supports the following activities:

Developing candidate therapeutic entities (e.g. drug discovery)
Pre-clinical testing of novel therapeutic entities
Early-phase clinical studies of novel therapeutic entities (phases 1 and 2)
“Repurposing” clinical studies, using existing therapies for new indications
Developing and testing novel devices
Developing and testing diagnostics (including biomarker validation where the intent is for diagnostic use)

Individual projects can start and finish at any point along this range, although we would not normally expect to support a project from initial development through to phase 2 clinical testing in a single application (sequential applications are encouraged, however, where there is a justified need for continued support).

All disease areas (including those relevant to global health) and modalities of intervention are eligible for support from the scheme, including small molecules, peptides, antibodies, vaccines, gene therapy, devices, surgical techniques and psychological approaches.

Stem cell-based projects are not eligible for support, as they are funded through the MRC’s Translational Stem Cell Research Committee.

The following activities are ineligible for support under the DPFS/DCS scheme:

Fundamental or investigative research not linked to a development plan (best supported by the Research Boards
Clinical studies where the primary purpose is to investigate disease mechanism (best supported by the Research Boards
Late-phase clinical trials (supported by the MRC-NIHR Efficacy, Mechanisms and Evaluation scheme and the NIHR Health Technology Assessment scheme)
Late-phase global health trials (supported by the MRC Global Health Trials Programme and the DfID-Wellcome Trust-MRC Joint Global Health Trials Scheme)

Funding available

The DPFS/DCS scheme has an annual budget of over £40m per year. We would normally expect applications to be substantive and therefore seeking a minimum of £250k in costs. There is no formal upper limit on project costs, but applicants will be required to justify costs based on the needs of the individual project. Likewise, duration should be based on the needs of the project. As broad guidance, pre-clinical projects are likely to be around 2 years in duration, with clinical projects frequently requiring support for a longer period.

Awards are subject to up to 4 key milestones (go/no-go decisions). This allows risk to be managed appropriately, and enables projects to be supported when later stages of the work are dependent on the success of earlier stages. Failure to meet a milestone may lead to early termination of funding.

Eligibility

The normal MRC eligibility rules apply; please see the applicants’ handbook and the Research Councils UK website.

Research council units and institutes (including MRC units) can apply to this scheme.

In addition, the following conditions apply to this scheme:

Individuals may be the principal investigator (the named, lead applicant) on one application per round. Individuals can act as co-applicants or collaborators on any number of applications per round. However, please note that the assessment will consider the level of engagement of co-applicants and collaborators with the research and their capacity to meet these requirements.
There is no limit to the number of applications per higher education institution (HEI) or research institution, but capacity to conduct the study will be considered during assessment.

Collaborations

Applications including partnerships with charities or industry are encouraged where these add value to the project – for example, in terms of access to expertise, technologies, reagents or funding. The MRC does not have the capacity to broker these arrangements.

Applications involving collaboration with industry should adhere to the MRC Industry Collaboration Agreement guidance. The lead applicant must be the academic partner, and the MRC will meet the academic costs of the project only.

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.

For advice on collaborative projects, contact:

For pre-clinical projects: jonathan.pearce@headoffice.mrc.ac.uk

For clinical projects: tom.foulkes@heaoffice.mrc.ac.uk

Costs

Proposals are funded on the basis of 80% of the full economic cost (except for “exceptional costs”, which are funded at 100% - see the applicants’ handbook). The MRC will meet the academic costs of the project only.

Applications including a clinical trial should include the cost of the International Standard Randomised Controlled Trial Number (ISRCTN) registration. Costs relating to patenting are not eligible for support.

NHS* costs

Applicants should refer to the AcoRD guidance to ensure that research costs, NHS treatment costs and NHS support costs are correctly attributed. In particular, applicants should note that drug costs in “repurposing” clinical studies are generally considered to be NHS treatment costs; drug costs for unlicensed therapies are more likely to be research costs. Applications involving NHS costs are required to include a completed “Additional Costs Proforma: NHS Support and Treatment costs”.

*This guidance is applicable to England, Wales, Scotland and Northern Ireland.

Application process

Proposals will be assessed by a two-step process. A brief outline proposal will be reviewed by an expert panel. Successful outline applicants will be invited to submit a full application, which will undergo a further round of more detailed review. The total review time by the MRC for an outline and full application is expected to be approximately 26 weeks.

The DPFS/DCS panel contains members with expertise in fundamental and clinical research, therapeutic and diagnostic product development, commercialisation and intellectual property. The panel meets three times a year, eight weeks after the outline application deadline.

Outline applications

The purpose of the outline application is to ascertain whether the project’s aims, rationale, and deliverability are appropriate for consideration through the DPFS/DCS scheme. The outline application should be completed in partnership with your institution’s Technology Transfer Office (TTO), or equivalent, and failure to do so may prejudice your application.

The outline project plan should include up to 4 milestones, depending on project complexity. The criteria used to assess the project at each milestone should be chosen so that they address reasons for progressing or discontinuing the project, ensuring that the plan progresses along the critical developmental path.

The criteria by which the outline applications will be assessed are:

Clinical/medical need: Is the need significant and does the proposal have an advantage over competing solutions?
Rationale: What is the strength of the rationale and supporting evidence for why the proposed solution will meet the targeted need?
Deliverability: Is the proposed development plan realistic? Will it answer the question or address the need identified? Does it offer good value for money? Does the team have access to the necessary assets and expertise to deliver the planned work?
Intellectual Property: Is there an appropriate intellectual property strategy in place to optimise the chances of downstream funding/partnering? Note that projects that will not generate patentable materials but that will nevertheless be able to provide health benefits are accepted on an equal basis.

Further guidance is provided in the guidance for outline stage applicants. Successful outline applicants will be invited to submit a full application using a DPFS/DCS full case for support form which will be provided by the MRC.

Full applications

The purpose of the full application is to assess in greater depth the need being targeted and the proposal’s rationale, and to establish whether there is a robust development plan in place to deliver the project goals.

The full application should be completed in partnership with your institution’s Technology Transfer Office (TTO), or equivalent, and additional external experts as required. Failure to do so may prejudice your application.

The criteria by which the full applications will be assessed are:

The significance of the need the proposal is seeking to address and competitive advantage.
Potential impact of the research
The quality of the proposal’s rationale and approach
Robustness of the design, methodology and analysis plans to address the research questions
The feasibility and appropriateness of the project plan: Project start points; Project objectives; Costs, tasks, deliverables, and schedule; Value for money, Adequacy of the risk management plan
Project objectives
Costs, tasks, deliverables, and schedule
Value for money
Adequacy of the risk management plan
Appropriateness of the project management plan: Project management group membership and experience, Assignment of responsibility within the project team, Key performance indicators (for example, time, cost), Suitability of the exploitation strategy
For clinical studies, the ability of the team to design and deliver a methodologically robust study will be a key assessment criterion.
Applications must demonstrate a strong understanding of the regulatory environment and the requirements for good clinical practice and research governance. Ethical issues must be addressed appropriately.

All outline and full-stage applicants will receive feedback from the assessment process. Please note that the decisions of the panel will not be open to appeal and that the MRC reserves the right to amend the application process.

Oversight

To ensure effective delivery of the proposal’s objectives, successful proposals will be required to establish an appropriate project management group and reporting system.

During the period of support, the project management group will be required to submit Project Milestone and End Reports to the MRC. If a milestone is at risk of not being met, the project management group may submit a request for change, proposing a resolution to the issues they face. Project Milestone Reports, End Reports and requests for change are reviewed by the MRC. Projects which fail to meet milestones may be terminated.

Selected studies may be deemed to require additional oversight by the MRC. For a small proportion of awards, on a case-by-case basis, the MRC will establish an oversight group to monitor progress against milestones.

Intellectual property

Note that the generation of intellectual property is not an essential requirement for this scheme; projects that will not generate patentable materials but that will nevertheless be capable of providing health benefits are accepted on an equal basis.

Intellectual property generated in the course of a project will 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.

The MRC wishes to assure itself that host institutions are able to manage and exploit effectively the intellectual property generated from MRC-funded research. This is particularly important in the case of the DPFS/DCS scheme, as projects will likely require further development in order to meet their ultimate clinical aims.

To understand the effectiveness of intellectual property management, the project management group will be asked to submit, as part of their Project Milestone and End Reports, details of the intellectual property generated during the course of the project and of the management and exploitation of this intellectual property. The MRC will also require the Principal Investigator to submit an annual follow up report on downstream outcomes of intellectual property for up to three years after the project end date.

How to apply and timings

Outline applications must be submitted via the Je-S system using the DPFS/DCS outline case for support form in conjunction with the guidance for applicants.

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.

Application deadlines are usually in March, July and November for consideration by the Panel at its meetings in May, September and January respectively.

Your proposal must be submitted through the MRC Je-S system by 4pm on the relevant deadline date.

Information on the full application process will be provided to successful outline applicants by the MRC.

Ethics and governance

The MRC does not require ethics permissions and regulatory approvals to be in place when you submit an application. However, given that research 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 may be required to ensure that all requirements can be met in a timely manner. Once an application is successful, it is the responsibility of your host institution to ensure that the appropriate ethics approval(s) has been obtained and that no research requiring such approval is initiated before it has been granted. Please read the MRC terms and conditions for further details.

Additional guidance

Applicants should review the MRC Applicants’ Handbook and DPFS/DCS Guidance for Outline Stage Applications

Applicants proposing a clinical study are referred to the following literature on experimental medicine methodology and governance in developing their research plans:

Royal Statistical Society’s Working Party on Statistical Issues in First-in-Man Studies
EM Toolkit
EMEA guidance on high risk, first-in-man clinical trials

Publishing results

Results of MRC-funded clinical studies (whether positive or negative) must be published within a reasonable period* following the conclusion of the study. Results should be reported in accordance with the recommendations in the CONSORT statement [Schulz et al. BMJ 2010;340:c332]. Data should be made available in line with the MRC Data Sharing Policy.

*Generally within a year of completion