This is a brief of broader scope from which the participating programmes may be interested in potentially funding more than one proposal. Applications should be within the remit of either:
- MRC-NIHR Efficacy and Mechanism Evaluation (EME) Programme
- Health Technology Assessment (HTA) Programme
More information on identifying the appropriate funding source for your clinical study or trial is available.
We are interested in proposals for the evaluation of strategies and interventions for the withdrawal of immunomodulatory therapies in conditions involving long-term treatment, to optimise efficacy and effectiveness. Studies should focus on the potential clinical benefit to patients, such as disease-specific outcomes or reducing treatment-related morbidity without compromising efficacy. Applicants should clearly define and justify their choice of patient group, study design and outcome measures, and explain how the research will fit into the remit of the programme.
For the EME Programme, applications are expected to detail the scientific rationale and proof of concept for the strategy, which may include the proposed mechanism whereby the strategy may improve patient outcomes. Applicants are encouraged to consider opportunities to embed the testing of mechanistic hypotheses within the main study.
For the HTA Programme primary research, including randomised and hypothesis-testing observational studies, and evidence syntheses will be considered. We are looking for studies where there is equipoise around the advantages and risks of continued treatment, with the potential to change clinical practice.
Examples of topics of interest include, but are not limited to:
- studies concerning the optimisation of treatment schedules, as in shorter courses of treatment or reducing the dosage of long-term therapies
- evaluating the safety and effectiveness of withdrawing treatments associated with increased risks at particular timepoints, for example leading up to surgery or during pregnancy
- evaluating interventions or tests to identify individual patients unlikely to benefit from continued treatment, or who may otherwise benefit from de-escalation of treatment
- reducing treatment burden associated with polypharmacy
- studies that employ innovative designs, or make use of real-world data
- evaluating the accuracy of interventions (tools or tests) to identify individuals who may benefit from de-intensification of treatment
- withdrawal of long-term treatments, where the strategy itself (with or without additive treatment) may have a clinically beneficial or disease-altering mechanism of action
- novel interventions to improve or facilitate de-escalation or withdrawal of treatments
Applications to this call are expected to evidence strong patient and public involvement (PPI) from an early stage, particularly around the acceptability of the proposed treatment strategies and feasibility of recruitment. Applicants may also wish to consider proposing an initial embedded pilot/feasibility study.
Rationale
For some interventions that are known to be effective, the optimal dose and duration of treatment remains unclear. The issue of risk-benefit analysis is particularly complex for those treatments associated with serious adverse events or side-effects. Where there is clinical equipoise around the possible risks and advantages associated with continued treatment, there may be a rationale for research into treatment deintensification, which aims to decrease treatment-related morbidity without compromising efficacy.
Total expenditure on medicines in England by the NHS in 2020/2021 was estimated to be £16.7 billion (source: NHS BSA). Malignant Disease and immunosuppression had the highest spend across all settings of £2.80 billion, equating to 16.3% of the total spend. Of this £2.61 billion was for medicines issued and dispensed in hospitals.
The aim of this brief is to address research questions around optimising care for patients who may be experiencing overtreatment with immunomodulatory therapies. For the purposes of this brief, overtreatment is considered to be the continuation of long-term treatment for which a diagnosis is ‘correct’, but the treatment has an uncertain probability of benefitting an individual patient further. This does not include issues of over-diagnosis.
Outcomes are expected to centre around benefits to patients, such as the mitigation of adverse events and improving quality of life. Although not the focus of this call, resource use and cost savings to the NHS are likely to form part of any effectiveness analysis.
We are inviting applications to evaluate novel interventions in this area with human proof of concept to suggest a signal of efficacy, but efficacy remains an uncertainty (EME Programme) or applications addressing research uncertainties relating to current practice (HTA Programme).
Making an application
If you would like to apply for this funding opportunity, you can begin your application via the funding opportunity page.
Your application must be submitted online no later than 1pm on the 15 May 2024. Applications will be considered by the HTA Funding Committee at its meeting in July 2024.
Guidance notes and supporting information for HTA Programme applications are available.
Shortlisted Stage 1 applicants will be given eight weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in November 2024.
For commissioned topics, the Programme strongly discourages the practice of the same co-applicant joining more than one competing team, other than in unusual circumstances (for example, a lead from a named charity or a unique national expert in a condition).
For such exceptions, each application needs to state the case as to why the same person is included. The shared co-applicant should not divulge application details between teams, and both teams should acknowledge in their application that they are aware of the situation, and that study details have not been shared.
Should you have any queries please contact htacet@nihr.ac.uk.