Introduction
The aim of the 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 intensive weight management versus standard lifestyle advice, with or without metformin, for prevention and management of metabolic morbidity in women and others with PCOS?
- Intervention: Intensive weight management (applicants to consider how to account for any use of metformin).
- Patient group: Adults with Polycystic Ovary Syndrome (PCOS). Applicants to define and justify an appropriate BMI range(s). Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field.
- Setting: Primary care, with recruitment from any appropriate setting.
- Comparator: Standard lifestyle advice (applicants to consider how to account for any use of metformin).
- Study design: A randomised controlled trial with an internal pilot phase to test key trial processes, such as recruitment and adherence. A factorial study design may be appropriate. Clear stop/go criteria should be provided to inform progression from pilot to full trial.
- Important outcomes: Cost-effectiveness; Weight; Waist circumference; BMI; Glucose tolerance and insulin sensitivity; Hirsutism score; Menstrual regularity; Quality of life; Mental health; Adverse events; Acceptability of the intervention to recipients.
- Other outcomes: Applicants to define and justify. Might consider: Outcomes related to obstructive sleep apnoea and non-alcoholic fatty liver disease; Blood pressure; Lipid profile; Androgen profile; Time spent on hair maintenance; Sexual wellbeing; Acne severity; Change in muscle mass; Body fat percentage; Activities of daily living; Sustainability of weight loss; Measures of eating behaviour and attitudes.nExisting Core Outcomes should be included amongst the list of outcomes unless a good rationale is provided to do otherwise. Applicants are expected to consider any demographic factors that may be relevant and report recruitment and findings disaggregated by these factors.
- Minimum duration of follow-up: 12 months. Applicants to define and justify.
- 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.
The NIHR recognises that people have diverse gender identities, and in this research brief, the word ‘women’ is used to describe patients or individuals whose sex was assigned at birth as female, whether they identify as a woman, a man, or non-binary.
Rationale:
Polycystic ovary syndrome (PCOS) is a common condition that affects how a woman’s ovaries function, affecting 1 in every 10 women in the UK.
Symptoms of PCOS include: irregular periods, difficulty getting pregnant, excessive hair growth on the body, weight gain, hair loss from the head and acne. Whilst the cause of PCOS is not currently known, several factors are thought to play a role, including: insulin resistance, abnormal hormone levels, weight and hereditary factors.
In addition to its effects on reproductive health, PCOS is now established as a metabolic disorder characterised by defects in insulin secretion and action. Women with PCOS are at an increased risk of progression to multiple morbidities including type 2 diabetes, gestational diabetes, non-alcoholic fatty liver disease, obstructive sleep apnoea and cardiovascular diseases. Insulin resistance and weight gain are 2 key modifiable drivers of this progression, however there is limited evidence as to whether lifestyle modification and/or metformin manages and reduces this risk of multimorbidity.
Recent systematic reviews have reported that existing studies are of low-quality and limited by small sample sizes, risk of bias and short treatment duration. This therefore signifies an important evidence gap. Studies focusing on intensive weight management programmes have displayed effective weight loss which has been shown to improve dysglycaemia, insulin sensitivity, and reduce the progression to type 2 diabetes, highlighting the potential utility of such an approach in populations at risk of multiple morbidities, including those diagnosed with PCOS.
The HTA programme wishes to commission a trial to determine the effectiveness of intensive weight management programmes on preventing and managing metabolic morbidities in women with PCOS. It is expected that applicants include within their proposals the outcome measures that are most important to this patient group.
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 htaresearchers@nihr.ac.uk.
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 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 8 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