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21/607 Mechanisms of action of health interventions in patients with multiple long-term conditions (MLTC)


Published: 08 December 2021

Version: 1.0

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MRC-NIHR funding collaboration

The Efficacy and Mechanism Evaluation (EME) Programme invites applications for research into the mechanisms of action of health interventions in studies recruiting patients with multiple long-term conditions (MLTC). The NIHR has published a strategic framework for research into multiple long-term conditions (MLTC), which sets out what we mean when we talk about MLTC research.

The proposed research may involve the analysis or reanalysis of previously stored specimens or data. For eligible studies (see below), the project may involve the collection of new specimens or new data for analysis, provided it is obtained from the original study participants.

Proposals will be accepted across a wide range of interventions including behavioural, pharmaceutical, psychological, surgical and public health interventions. The research should be hypothesis-driven, relevant to the intervention and outcomes proposed by the original study and add significantly to the scientific understanding of the mechanisms of action of the intervention in the particular context of MLTC. Applications exploring methodological approaches for efficacy trials including populations with MLTC are encouraged.

Applicants will need to make a strong case for how a better understanding of the mechanisms of action will potentially contribute to the future use or development of the technology, future wealth creation and for the ultimate benefit of individual patients’ or the wider NHS.

Areas of particular interest include, but are not limited to:

  • Projects which focus on the mechanisms underpinning a heterogeneity of treatment effect between MLTC-based sub-groups within the study. These groups may have been included by design or identified following post-hoc analysis.
  • Hypotheses relating to interactions between treatments in patients with MLTC, which may include phamocokinetic/pharmacodynamic interactions.

Study eligibility

Studies must utilise patients or samples from identifiable and eligible cohorts, which must be from one of the following:

  • Non-NIHR funded projects, only where recruitment has been completed. Examples include projects funded by UKRI (e.g. MRC, Innovate UK), Wellcome and major charities. All projects must have been through an external peer review process and we may request evidence of this. The remit would also include NIHR/MRC/Wellcome or equivalent fellowships, provided the sample sizes are sufficiently large. Alternatively, samples from fellowships could be incorporated into a larger pool of samples.

Applicants must provide evidence of data sharing agreements with the owner(s) of any data required for the proposed mechanistic study or agreement from the chief investigator of the original study if it was NIHR-funded. If the original Chief investigator is not the chief investigator or a co-applicant on the mechanistic study then a supporting letter will be required at Stage 2.