Efficacy and Mechanism Evaluation

The Efficacy and Mechanism Evaluation (EME) programme funds ambitious studies evaluating interventions with potential to make a step-change in the promotion of health, treatment of disease and improvement of rehabilitation or long-term care. Within these studies, EME supports research in the mechanisms of diseases and treatments. EME is a partnership between the MRC and NIHR.

co-funded by the MRC

It looks to attract studies with novel methodological designs that deliver results more efficiently, reduce the study timeline, and maximise the knowledge gained. The translational research it supports covers a wide range of new and repurposed interventions, such as diagnostic or prognostic tests and decision-making tools, therapeutics or psychological treatments, medical devices, and public health initiatives delivered in the NHS.

All of our funded projects are eligible for publication in the NIHR Journals Library. This open access resource is freely available online, and provides a full and permanent record of NIHR-funded research.


The EME Programme primarily supports clinical trials, and other robustly designed studies that test the efficacy of interventions. The interventions should have the potential to improve patient care or benefit the public.  The programme will only support studies where there is sufficient evidence that the intervention might work in man, i.e. that there is ‘proof of concept’. 

Innovative study designs involving stratification, the use of routinely collected digital data or novel methodologies are strongly encouraged.

Where appropriate, the programme encourages hypothesis-testing mechanistic studies integrated within the main efficacy study.  These studies could explore the mechanisms of action of the intervention, the causes of differing responses, or promote an understanding of any potential adverse effects and how these could be reduced; they could also contribute to understanding of the disease. The programme will also support mechanistic studies that follow on from on-going or completed clinical studies funded by the NIHR which can use data or samples from these studies. These can include qualitative research and opportunities for mechanistic work where the efficacy trial has not been successful.

The programme will accept applications for studies that use clinical or well-validated surrogate outcomes.  It will also consider studies that validate potential surrogate outcomes against a primary clinical outcome, within the main clinical trial. 


The EME Programme will support...

  • Research to determine proof of clinical efficacy, size of effect, and long-term safety in a well-defined population.
  • The evaluation of a broad range of interventions that have the potential to maintain health, treat disease or improve recovery.
  • Hypothesis-testing research based on an efficacy study, to explore the mechanisms of action of interventions, causes of differing responses or disease mechanisms. These studies use data or samples obtained and stored from both treatment and control groups of a clinical study, to arrive at conclusions that would not arise from a simple cohort study.

Proposals may include two stages with progression to the main clinical evaluation dependent on the outcome of the previous stage, measured against predefined criteria. The main clinical evaluation must start within 18 months of the project start date and should account for more than 75% of the total project cost.

The work supported by the first 25% tranche of funding could include:

  • Early phase studies and trials aimed at understanding mechanisms to inform the main study. We would fund research in this category to include studies where a drug improves the clinical state of patients with a genetically determined illness but the effect of the drug on gene product production has not been determined. Similarly, cell therapy treatments where symptomatic improvement has been noted but the specific action of the cells in the disease is unknown would qualify.
  • Retrospective sample analysis where the data is needed to inform the main study
  • Late stage development to facilitate moving the intervention from pre-clinical and early human studies to delivering the intervention in a clinical setting (see example 1 and example 2)
  • Pilot or feasibility studies (see example)

Staged studies will require predefined stop/go decision points, with measurable criteria to enable assessment of the successful completion of the stage.  Studies may on occasion, be reviewed by the EME Board at the end of each stage before progression to the next stage.

  • Pilot and feasibility studies where the main study would be within the remit of the EME Programme. These studies may be either stand-alone or can be the initial part of a staged project that includes the main clinical evaluation as a subsequent stage. 
  • The limited steps needed to progress the development of an intervention to a stage suitable for use in an accredited clinical service when included as an initial stage prior to commencing the main clinical evaluation.
  • Studies using novel or infrequently-used study designs that increase the value of a study, by maximising the chances of demonstrating the benefit of an intervention, increasing the knowledge that can be gained through the study, or by making the study more efficient.


The EME Programme will not support

  • Large effectiveness studies that test the impact of the introduction of an intervention in the wider NHS (our HTA Programme may be more suitable).
  • Hypothesis-generating studies based on sample or data collections from patient cohorts.
  • Confirmatory studies, equivalence studies, 'confidence in effect' studies or studies of incremental modifications to existing interventions.
  • Research into areas where the health need is primarily outside the UK. 
  • Any research involving animals or animal tissues (see our animal testing page for more information).


Fast-track scheme

Most research supported by the EME Programme will follow the routine two-stage process of assessment before being funded. However, it may sometimes be necessary to accelerate the handling of a research question and in such circumstances researchers may be eligible to apply through the fast-track scheme.

The fast-track scheme provides an opportunity to submit a full proposal directly, shortening the length of time it takes for a funding decision to be made. However, please bear in mind that proposals accepted onto the fast-track scheme will compete on equal terms with other full proposals which have had the benefit of feedback by the Funding Board at outline stage.

It is intended that this route is only used where reducing the timescale will provide significant benefit, or exploitation of a narrow window of opportunity, for example:

  • where the application process adds significantly to the time taken to answer the research question
  • when the study team have received previous funding from another funder, at an earlier stage, for the intervention being evaluated
  • a pilot or feasibility study (which if positive would lead to an application to the EME Programme for a full study).

If you would like your proposal to be considered for the fast-track scheme, please contact eme@nihr.ac.uk. You will be asked to:

  • convince the secretariat that there is significant benefit to fast-tracking your application, and
  • submit a written summary of your proposal (usually about one side of A4) in a PICO format, together with a description of the existing proof of concept.

The information you provide will then be considered and you will be informed whether your proposal is eligible for fast-tracking. You will then be provided with more information about submitting your full application and the timescales for doing this.


Study example

The REACT trial led by Dr Kathryn Beardsall, University of Cambridge, in collaboration with Medtronic is investigating whether real time continuous glucose monitoring in preterm infants could help clinicians to control blood sugar levels more easily. Premature babies have difficulty controlling their blood sugar and prolonged instability can lead to brain injury. The trial uses a new device which can provide a constant reading and be less invasive compared to current methods which involve taking regular blood samples. The following video was produced by the project team for families and explains more about the study.


Contact us

We offer a wide variety of assistance during all stages of the research process. If in doubt, please get in touch.


The EME programme is funded by the MRC and NIHR, with contributions from the Chief Scientist Office (CSO) in Scotland, Health and Care Research Wales and the HSC R&D Division, Public Health Agency in Northern Ireland.