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
What is the clinical and cost-effectiveness of treatment with tofacitinib compared with infliximab for people with active steroid-resistant ulcerative colitis?
- Intervention: Tofacitinib.
- Patient group: Adults with active steroid-resistant ulcerative colitis (applicants to define and justify inclusion criteria for ‘steroid-resistance’ in the patient group).
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: Secondary care setting.
- Comparator: Infliximab (subcutaneous and/or intravenous). Applicants to define and justify the use of either or both.
- 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:
- quality of life
- steroid-free remission (applicants to define and justify what outcome measure is to be used e.g. Mayo score).
- Other outcomes:
- adverse effects
- cost-effectiveness
- colectomy rates
- infection rates
- malignancy rates
- venous thromboembolism rates
- 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 appropriate length of follow-up.
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
Ulcerative colitis (UC) is a type of inflammatory bowel disease characterised by chronic inflammation of the colon and rectum. This inflammation occurs during ‘flare-ups’ where symptoms such as abdominal pain and bloody, loose stool can occur. These symptoms can have a significant impact on a patient’s quality of life. There is currently no known cause for a patient developing this disease and it is estimated that in the year 2020 there were ~500,000 people in the UK living with UC.
There are several treatment options available for UC, many of which have adverse side-effects when used long-term. The primary goal of treatment is to minimise symptoms, ultimately achieving remission and improving patients’ quality of life. Treatment typically starts with aminosalicylates such as mesalazine and corticosteroids. If the patient does not achieve symptomatic remission after use of steroids, they are then considered to have steroid-resistant/refractory UC. In cases of steroid-resistant UC, the most popular treatment is the use of biologics which are strong anti-inflammatory medications. The most common of which is tumour necrosis factor a (TNF-a) inhibitors such as infliximab.
A newer approach to UC treatment which has shown effectiveness are Janus Kinase (JAK) inhibitors, the most popular being tofacitinib. Tofacitinib is recommended by NICE as a treatment option for patients with active moderate to severe UC when conventional therapy or use of a biologic agent has not been tolerated by the patient or the disease has either not responded sufficiently or not at all.
Currently there are no head to head trials of infliximab and tofacitinib for steroid-resistant UC. The HTA Programme would be interested in commissioning research to examine the performance of these two treatments within 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, we aim 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 22 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 htagb@nihr.ac.uk.