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 giant cell arteritis treated with tocilizumab, what is the clinical and cost-effectiveness of continuing versus discontinuing tocilizumab after 12 months of treatment?
- Patient group: Adult patients with giant cell arteritis treated with tocilizumab for 12 months.
Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field. - Intervention: Tocilizumab treatment beyond 12 months, with applicants to define and justify potential treatment regimens to test. Oral glucocorticoids (for example prednisolone) can continue.
- Control: Discontinuing tocilizumab at 12 months as per current guidance. Oral glucocorticoids (for example prednisolone) can continue.
- Important outcomes: Relapse; glucocorticoid dose; quality of life; visual loss; adverse events, including glucocorticoid-related adverse events; cost-effectiveness. Other outcomes: Healthcare use; appropriate imaging outcomes to be considered. 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.
- Setting: Rheumatology out-patient clinics.
- 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.
- Minimum duration of follow-up: Applicants to define and justify.
Rationale
More common in women than men, giant cell arteritis (GCA), also called temporal arteritis, is the most common systemic vasculitis affecting people older than 50 years of age and results from inflammation of within the walls of medium and large sized arteries.
Common GCA symptoms include vision loss, double vision, jaw and tongue pain, scalp tenderness, headaches, anorexia, fever, and weight loss. Reduction in the blood supply to the eyes is usually the most serious complication and can lead to blurred vision, or in some patients, blindness, although reduction of the blood supply to the brain can also cause stroke.
Glucocorticoids (a class of steroid hormones), usually prednisolone, are the mainstay of treatment for GCA, but can themselves have numerous and serious side effects. This is usually then tapered to zero over 12-18 months providing there is no return of GCA symptoms, signs or laboratory markers of inflammation.
Tocilizumab (trade name Actemra or RoActemra, Roche Products Ltd), an interleukin-6 receptor inhibitor monoclonal antibody, in combination with a tapering course of glucocorticoids, is now also recommended for use in GCA but treatment duration is limited to 12 months based on the current very limited evidence base and cost-effectiveness data beyond this point.
During the COVID-19 pandemic NHS England established a rapid policy development process and introduced an interim policy proposition which provided an option for some patients on tocilizumab for GCA nearing the end of their prescription to continue past 12 months treatment, but this temporary provision ended in April 2022. There is considerable interest within the rheumatology community to investigate the role of tocilizumab beyond the current 12 month funded limit of treatment.
While there is limited data on longer term treatment with tocilizumab in GCA, most notably from the open label extension of the GiACTA trial (which provided the majority of the evidence for tocilizumab in GCA and on which NICE and other guidelines are based), the lack of blinding and randomisation in this part of the study place inherent limitations upon such data. Answering these questions on tocilizumab treatment duration beyond 12 months will be important for patients, physicians and public policy makers and will only be answered with an appropriately powered randomised controlled trial.
To support the ambitions of NIHR’s Best Research for Best Health: the next chapter, NIHR strongly encourages the inclusion of nurses, midwives and allied health professionals within well-developed research teams responding to this call, to increase the building of nurse, midwife and allied health professional-related research activity, capacity and capability across the 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
Your application must be submitted online no later than 1pm on 26 July 2023. Applications will be considered by the HTA Funding Committee at its meeting in September.
HTA Programme Stage 1 guidance notes are available, alongside supporting information for applicants.
Please note, 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 January 2024.
Applications received electronically after 1pm on the due date will not be considered.
For commissioned topics, the Programme strongly discourages the practice of the same co-applicant joining more than one competing team. There may be unusual circumstances where the same person could be included on more than on application, 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. Both teams should acknowledge in their application that they are aware that one of their co-applicants is part of a competing application and that study details have not been shared.
Should you have any queries please contact htacommissioning@nihr.ac.uk.