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23/168 Higher-calorie refeeding compared with lower-calorie refeeding in malnourished adults with anorexia nervosa commissioning brief


Published: 30 November 2023

Version: 1.0 November 2023

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The aim of the Health Technology Assessment (HTA) Programme is to ensure that high quality research information on the clinical effectiveness, cost-effectiveness and broader impact of healthcare treatments and tests are produced in the most efficient way for those who plan, provide or receive care from NHS and social care services. The commissioned workstream invites applications in response to calls for research on specific questions which have been identified and prioritised for their importance to the NHS, patients and social care.

Research question

What is the clinical and cost-effectiveness of higher-calorie refeeding compared with lower-calorie refeeding in malnourished adults with anorexia nervosa who have at least one risk factor for refeeding syndrome?

  1. Patient group: Adults with a diagnosis of anorexia nervosa who are malnourished and require inpatient refeeding, and have at least one risk factor for refeeding syndrome. Applicants to define and justify exact inclusion and exclusion criteria. Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field. 
  2. Intervention: Higher calorie refeeding, for example, 30-35kcal/kg per day. Applicants to define and justify exact amount and method of refeeding.  
  3. Comparator:  Lower calorie refeeding, for example, 10-20kcal/kg per day. Applicants to define and justify exact amount and method of refeeding.
  4. Important outcomes:  Refeeding hypophosphatemia; instances of refeeding syndrome; time to establishment of target feeding rate (in days); cardiovascular measures; assessment of biochemical and haematological responses to refeeding; weight measures such as weight change, BMI, percentage mBMI; length of hospital stay; readmission, number of readmissions; quality of life; mental health; adverse events; death; cost-effectiveness. Existing Core Outcomes should be included amongst the list of outcomes unless a good rationale is provided to do otherwise. Applicants are encouraged to report recruitment and findings disaggregated by sex, plus other demographic factors where relevant.  
  5. Setting: Secondary care. Applicants should include a range of secondary care settings, for example, medical units, specialist eating disorder units and clinical nutrition units. 
  6. Study design: A randomised controlled trial with an internal pilot phase to test key trial processes such as recruitment and adherence. Clear stop and go criteria should be provided to inform progression from pilot to full trial. Applicants may wish to consider subgroup analysis, for example by the number of risk factors for refeeding present.  
  7. Minimum duration of follow-up: Minimum follow-up of 1 year from randomisation, but applicants should define and justify the most appropriate timing of the primary outcome measure. Longer-term follow up: If appropriate, researchers should consider obtaining consent to allow potential future follow up through efficient means, such as routine data, as part of a separately funded study.


Anorexia nervosa is an eating disorder and serious mental illness. People with the condition try to keep their weight as low as possible by either reducing their food intake or through excessive exercise, or by both. This can lead to malnutrition and serious illness. Anorexia nervosa has the highest mortality rate of all psychiatric illnesses.

A person with anorexia nervosa who is seriously malnourished is in a life-threatening state and may require inpatient refeeding. Refeeding is the provision of calories with the aim to restore physiological stability through weight gain.  

However, there is risk associated with refeeding, namely refeeding syndrome. Refeeding syndrome encompasses the clinical and biochemical problems that may result from the reintroduction of nutrition rapidly to people who are malnourished and can be potentially fatal.  Hypophosphatemia (a condition in which blood has a low level of phosphorus) is the most common symptom and is one of the earliest clinical indicators of the onset of refeeding syndrome.  It has many effects including muscle weakness, biventricular cardiac failure and arrhythmias.  

Therefore, refeeding has been approached with caution since refeeding syndrome was first identified over 80 years ago. This has meant that refeeding has begun at a lower calorie level with the aim to prevent refeeding syndrome occurring. In recent years, however, this approach to refeeding in people with anorexia nervosa who are malnourished has been questioned. It is suggested that lower calorie rates of refeeding are associated with initial weight loss, slow weight gain and prolonged hospital stays. This is characterised as underfeeding and may inadvertently prolong the acute risk of potentially life-threatening undernutrition. Evidence, especially in adolescents, suggests that refeeding for some people can begin at higher rates than previously thought without an increased risk of refeeding syndrome or other complications.

The Royal College of Psychiatrists has recently produced updated guidelines in the area: Medical Emergencies in Eating Disorders: Guidance on Recognition and Management. It sets out the existing evidence and highlights the clinical uncertainty about whether refeeding should begin at a lower or higher calorie level. The guideline states that there is ‘an urgent need for a study of refeeding adults with anorexia nervosa in order to establish an evidence base for practice’. The HTA Programme is interested in commissioning research to address this uncertainty.  

Co-production, which ensures that the research demonstrates an equal partnership with service commissioners, providers and service users (or their advocates), should be embedded throughout the life cycle of the project from application to completion. Applicants may wish to consult the NIHR Learning for Involvement guidance on co-producing research.

To support the ambitions of NIHR’s Best Research for Best Health: the next chapter, we strongly encourage the inclusion of nurses, midwives and allied health professionals within well-developed research teams responding to this call, to increase the building of research activity, capacity and capability across these professions.

Depending on the level of experience, this could be through the role of lead applicant, as joint co-applicant supported by detailed mentoring plans submitted with the application, or as a co-applicant member of the research team. Through this activity, NIHR aims to support nurses, midwives and allied health professionals to become future research leaders and release the potential to lead, use, deliver and participate in research as a part of their job.

Additional commissioning brief background information

A background document is available that provides further information to support applicants for this call. It is intended to summarise what prompted the call and the existing evidence base, including relevant work from the HTA and wider NIHR research portfolio. It was researched and written on the basis of information from a search of relevant sources and databases, and in consultation with a number of experts in the field. If you would like a copy please email

Making an application

If you would like to apply for this call, you can begin your application via the funding opportunity page.

Your application must be submitted online no later than 1pm on 28 March 2024. Applications will be considered by the HTA Funding Committee at its meeting in May 2024.

Guidance notes and supporting information for HTA Programme applications are available.

Shortlisted Stage 1 applicants will be given 8 weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in September 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