Introduction
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
In patients with early moderate to severe systemic lupus erythematosus, is it more clinically and cost-effective to use rituximab first-line or after failure of conventional immunosuppressant therapies?
- Intervention: First-line rituximab.
- Patient group: Patients with early moderate to severe systemic lupus erythematosus. Applicants to strongly consider and justify the inclusion of both adults and children/young people.
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: Rheumatology out-patient clinics; Day case units; Inpatient wards.
- Comparator: Usual care. Applicants to define and justify.
- Study design: A randomised controlled trial with an internal pilot phase to test key trial processes such as recruitment and adherence. Clear stop/go criteria should be provided to inform progression from pilot to full trial.
- Important outcomes:
- Disease activity score (applicants to define and justify)
- Health-related quality of life.
- Other outcomes:
- Patient acceptability
- Treatment burden
- Organ damage
- Glucocorticoid exposure
- Need for other immunosuppressants/cyclophosphamide and biologic therapies
- Adverse events
- Number of infections
- 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 (and other demographic factors where relevant).
- Minimum duration of follow-up: 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.
Rationale
Systematic lupus erythematosus (SLE) also known as lupus, is a multisystem, chronic autoimmune disease whereby the immune system attacks the body’s tissues causing inflammation in the skin, joints and other organs. In severe disease, inflammation in the kidneys, lungs, heart and brain can cause serious damage. SLE causes a number of symptoms that can range from minor to life-threatening disease, for example:
- fatigue (can be severe and debilitating)
- malaise
- fever
- weight loss
- joint pain
- oral ulcers
- photosensitive skin rashes
The 2 most common symptoms of lupus are joint/muscle aches and pains and extreme fatigue – almost 90% of lupus patients report experiencing fatigue which can often cause substantial impairments in quality of life and work disability (Lupus UK).
Treatment for SLE aims to suppress inflammation, reduce symptoms and prevent organ damage. Due to the heterogeneity of SLE, current practice is variable and treatment options vary depending on severity. For most patients, symptoms are well managed using anti-inflammatory and immunosuppressive medications. Patients with severe, refractory disease may require treatment with a biological therapy such as rituximab, a monoclonal antibody that acts to deplete B cells. Rituximab is considered as a treatment option in patients with severe or moderate SLE who failed treatment with other immunosuppressive drugs.
There are several clear guidelines for the use of different therapies for SLE based on disease severity or organ involvement. However, there are no guidelines and little evidence regarding the sequence in which therapies should be used over time. Unlike other autoimmune diseases, in SLE the most severe disease, the highest mortality from disease activity, and highest healthcare utilisation often occurs early after diagnosis. This period therefore also entails greatest glucocorticoid exposure and greatest unmet need. It may therefore be inappropriate that current UK guidelines recommend rituximab is only to be used late in the treatment pathway. Currently biologic therapies are sometimes used much earlier, despite a lack of evidence for their use at this time. In the UK BILAG Biologic Registry for SLE, 14% of rituximab use was in the first year of disease and 27% with 2 years. The HTA Programme therefore wishes to commission the trial outlined above.
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 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 htacommissioning@nihr.ac.uk.