Higher-calorie refeeding compared with lower-calorie refeeding in malnourished adults with anorexia nervosa

The research question

Please provide a concise statement of your proposed research including how it fits our HTA Programme remit. 

You should include a clear explanation of the main (single) research question phrased in PICO terms where applicable to your study type:

• Population: NHS (or social care) target population i.e. real patients
• Intervention: A technology that is or could be used now in the NHS or social care. You may wish to refer to the Template for Intervention Description and Replication (TIDieR) guidance
• Comparator: Usually the next best treatment, but could be placebo
• Outcome: Patient/service user centred, leading to effectiveness and cost-effectiveness 

For some funding opportunities, much of this information will be detailed in the research specification. In this case, you should only provide any relevant additional information not already captured in the research specification. If you wish to propose a study that does not meet one or more of the requirements set out in the research specification, please use this section to explain the reasons for your approach.

Summarise your project plan plus any additional points required to support statements made in previous sections of your application. Include any key references required to justify them (for example, the use of particular outcome measures or methods of analysis).

Why is this research important in terms of improving the health and/or wellbeing of the public and/or to patients and health care services?

It is essential that you clearly identify the health and care need your research meets or contributes to. Please outline the anticipated value or contribution your study will provide. You must justify that this unmet need is a high priority to the NHS, social care or those who use these services. Your justification should be proportionate to the level of funding you are asking for. In some cases, substantive justification will be needed to prove your research is in an area of major importance. This includes detailing what support there is for this work from relevant clinical and patient communities.

Design

Dependent on the nature of the research you are undertaking, give a brief statement on the study design you will use, including:

• for primary research, state the health or care service setting(s) in which the study will occur. For example, general practice, hospital outpatients, ambulance service users, social care
• for secondary research or modelling, please explain the criteria applied to assess the quality and relevance of studies identified by the search strategy. Explain how these will be decided if these are not yet known

We welcome innovative methods that offer substantial benefits. If you plan to use a complex methodology, for example, Bayesian and model-based designs, you should justify this over a more standard approach. Benefits could include showing that the statistical properties are superior, or that the resources required are lower. You should also demonstrate that you have appropriate expertise within the research team to implement the approach. 

What is the evidence that the intervention is ready for HTA evaluation?

For some commissioned funding opportunities, we will have already reviewed existing evidence to inform the research specification. In this case please ensure you meet the requirements in the research specification. 

For researcher-led applications and commissioned funding opportunities with a broader scope, we require evidence that the intervention is ready for HTA evaluation.

You should present and reference relevant high-quality evidence synthesis such as systematic reviews, modelling studies and meta-analyses. Where no such published evidence synthesis exists, you are expected to undertake an appropriate review of the currently available evidence. You should do this using a predetermined and described methodology that systematically identifies, critically appraises and then synthesises the available evidence, and then present a summary of these findings in your proposal.

You should propose valid and reliable methods for identifying and selecting relevant material, assessing its quality and synthesising the results. See the NHS Centre for Reviews and Dissemination guidance for guidance on choosing appropriate methods.

If you are undertaking systematic reviews, please note our NIHR commitment to register these in the PROSPERO database. PROSPERO was developed by our NIHR’s Centre for Reviews and Dissemination (CRD). It is the first online facility to register systematic reviews for research about health and social care from all around the world. Access is completely free and open to the public. PROSPERO registration is a condition of NIHR funding for eligible systematic reviews. 

If your proposed study builds on previous work then the results of the previous study must be available to the Funding Committee before an application will be considered. Please reference the published results. If not yet published, the committee may ask to see the results, along with evidence of acceptance for publication, to demonstrate that peer review has taken place. 

Further to the guidance in the ‘Background and rationale’ section of the Research Plan, please justify the clinical importance of your proposed study to patients and the public, and outline the anticipated value or contribution the study will provide to clinical practice now and in future. You must justify that this unmet need is a high priority to the NHS, social care or those who use these services. Your justification should be proportionate to the level of funding you are asking for. In some cases, substantive justification will be needed to prove your research is in an area of major importance. This includes detailing what support there is for this work from relevant clinical and patient communities. In addition, please consider how your proposed intervention could be implemented across the wider NHS or social care settings. 

Target population and inclusion/exclusion criteria 

Clearly define the population from which the study sample receives the health technology concerned (or the control intervention where appropriate). For example, women over 60, people with a learning disability, people with advanced cancer. Please provide an explanation of the inclusion/exclusion criteria.

Health technologies being assessed 

Give a clear definition of the health technology to be assessed. The purpose of HTA is to assess the value of a health technology compared to best alternatives or where none exists, against no intervention. Where there are established alternative technologies, these should also be defined. Where the technology is subject to rapid change, you should include details of how this will be dealt with. 

Measurement of costs and outcomes 

Not all HTA studies require full economic evaluations. When considering including a cost-effectiveness analysis, you should carefully describe what this will add to the study. Where an economic component is proposed, you should aim to use the simplest approach, or fully justify where more complex methodologies are needed. You should justify the choice of outcome measures where a legitimate choice exists between alternatives. If your study includes a health economic component, state from what perspective costs and benefits will be considered, and (briefly) how these will be collected. Where established core outcomes exist, you should include these in the list of outcomes unless there is good reason to do otherwise. Please see the Core Outcome Measures in Effectiveness Trials (COMET) Initiative website to identify whether Core Outcomes have been established.

Longer-term follow-up 

You should consider obtaining consent from participants to allow you to follow-up with them in the future. This would be through efficient means (such as routine data) as part of a separately funded study. You should therefore consider building in provision for a mechanism to facilitate longer-term follow-up beyond the life of the main study, including obtaining consent for this from participants at study entry.

Sample size 

State the required sample size, giving details of the estimated effect size, power and/or precision employed in the calculation. You must provide this information so the Funding Committee can replicate the calculation and understand the assumptions made.

Difference between current and planned care pathways 

Please define the current standard care pathway and how this differs from the trial arms.

Diagnostics and imaging

You should justify where you consider improvements in diagnostic accuracy to be relevant. Where there is poor evidence to link diagnostic improvements to patient benefits, part of the primary research may be to assess the effects of such changes on patient management and outcomes. You should also assess changes in other resources (particularly other subsequent therapies) used as a result of changes in diagnostic methods.

Dissemination 

Our key concern is to ensure that projects funded by the HTA Programme are designed from the outset to produce useful, timely and relevant research findings which impact practice. 

Studies within a trial or review (SWATs/SWARs) 

You may apply for up to £30,000 funding to evaluate alternative ways of managing studies and how researchers can effectively engage with key stakeholders to promote the uptake and use of the evidence generated. This may be completed as part of your main study. Any methodological sub-study proposed should represent a very minor element of a larger study and must not undermine the delivery of the main study. There are some examples on the Northern Ireland Hubs for Trials Methodology Research web pages. 

You are also encouraged to review the work of Trial Forge. Where there are already a number of SWATs answering the same or similar question, substantial additional justification would be needed. You may want to consider collaborations with groups able to carry out methodological work, for example around such issues as evaluating sustainability outcomes for trials. SWATs/SWARs may not all be powered to provide meaningful outcomes but will be useful for meta-analysis and you should consider using protocols published on the Northern Ireland MRC Trials Hub for Methodology Research SWAT registry. If you wish to include a SWAT/SWAR in your study, you should indicate that you intend to do so in your Outline Application. There is no need to provide a detailed description of the SWAT/SWAR at this stage.

Multiple long-term conditions - studies within a project 

We encourage you to consider multiple long-term conditions (MLTC) studies within your project. This is to further understanding of MLTC, and improve knowledge on the best methods and processes for incorporating MLTC research questions into complex projects (including clinical trials) in health, social care and public health. You can propose an embedded study within a project (SWAP) which would support this. The study would be short and efficient, with findings put into the public domain as soon as they are available, as an interim output. A SWAP will be a small part of the overall application and should be costed at no more than £30,000 to include all dissemination and publication associated with the SWAP. You are not required to give a detailed description of the SWAP at this stage.

Mechanistic research 

We will support the collection of samples and data, where the HTA study provides an opportunity for valuable, hypothesis-testing research into the ‘mechanism of action’ of the intervention. The cost of sample collection and storage must be made clear in your application and must be modest in scale. Unless otherwise specified, any mechanistic work must be funded separately. You should note where there are plans to apply for and undertake the associated mechanistic study, for example via an application to the MRC-NIHR Efficacy and Mechanism Evaluation (EME) Programme. Any mechanistic work must not have a detrimental effect on the main study.

Project timetables including recruitment rate 

Indicate the anticipated duration of the study. Pay particular attention to the expected recruitment rate and justify your estimate. Outline the main stages of your proposed project including regulatory steps, team recruitment, patient recruitment, and the expected duration of each.

Expertise in your team 

The team should be multidisciplinary and include relevant expertise in the clinical area concerned. They should have expertise in performing evidence synthesis and (where appropriate) other areas. For example, experience in operational research, being a patient and public involvement (PPI) Lead, being a public voice with lived experience, a health economist or statistician. 

For commissioned topics, we strongly discourage 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.

Clinical Trials Unit involvement 

We advise that studies involving a clinical trial have engaged with an accredited Clinical Trials Unit (CTU) listed on the UKCRC CTU Network. Note that you must provide a letter of CTU support with all Full Applications involving a clinical trial. If you are designing or undertaking clinical trials, we encourage you to consult the Clinical Trials Toolkit.

Ethics/regulatory approvals

See the HRA website for guidance on the application process for ethical and other approvals. This process may vary depending where you are based in the UK. The HRA approval page provides more information. 
 
If you are using patient information from an existing database, please ensure you have consent or that appropriate exemptions are in place. Approval to use confidential patient information without consent must be requested from the HRA who make decisions with advice from the Confidentiality Advisory Group (CAG).

To take advantage of the growing utility of routine data, we encourage you to consider asking participants to consent to long-term follow-up. That is, beyond the outcomes of the HTA study where appropriate. 
 
See the UK policy framework for health and social care research for a summary of the responsibilities of key research stakeholders.

Medicines and Healthcare products Regulatory Agency (MHRA) considerations

The MHRA can provide guidance on the regulations that apply to your study. If you are planning a study on a medicine used outside its licensed indication, dose, or formulation, we encourage you to contact the Medicines Repurposing Programme for support and advice before submitting your application.