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 intravesical treatments for recurrent urinary tract infection (rUTI) in women?
- Intervention: Intravesical therapy or multiple intravesical therapies in a multi-arm trial (applicants to define and justify agent(s), dose, frequency, and duration).
- Patient group: Women with recurrent uncomplicated urinary tract infections (more than 2 episodes in 6 months, or more than 3 episodes in a year), who are being considered for daily oral antibiotics, a daily oral alternative to antibiotics, or any intravesical therapy to prevent further recurrence. Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field. Applicants should also specify how any barriers to participation will be addressed and what patient care will be offered, in particular with reference to repeated hospital attendance and undergoing an invasive procedure.
- Setting: Any appropriate setting (to be defined and justified by applicants).
- Comparator: Standard 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. Applicants are encouraged to propose trial designs that enable a comparative evaluation of 2 or more agents that may be used for intravesical preventative treatment of rUTI, or the same treatment administered in different doses or according to varying schedules (frequency and duration), to identify the optimal treatment regimen. Applicants should consider setting up an HTA sub-study looking at incidence of microbial resistance associated with each form of treatment. If feasible, applicants may also consider trial designs that enable differentiation between participants based on relevant characteristics that might further optimise treatment choices through informed prediction of success of intravesical therapies.
- Important outcomes: Applicants to define and justify the primary outcome, which should be patient focused. Outcomes of interest include (but are not limited to): patient-reported UTI symptoms; patient acceptability; general health-related quality of life; mental health; sexual wellbeing (intimacy with partner); medical contacts due to UTI; rates of antibiotic prescribing and use; development of antimicrobial resistance; complications; side effects; hospitalisation; cost effectiveness. Existing 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: To be defined and justified by applicants.
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
At least half of all women will experience urinary tract infection (UTI) at some point in their life and for a significant number of them the infection will keep coming back. This concerns women of all ages, can be very painful, and often affects not just physical wellbeing, but also mental health, relationships, and occupational performance.
As one of the most common forms of infection and one of the major drivers of antibiotic prescribing, UTIs also represent a major challenge for the NHS and for the public health authorities.
The current standard treatment for rUTI is a low daily dose of oral antibiotics, often taken over prolonged periods of time. Amid concerns about antimicrobial resistance, other options, such as cranberry products, D-mannose and methenine hippurate, have been investigated - with mixed results. For many women with rUTI, none of these oral treatments (antimicrobial or otherwise) work.
One promising alternative to oral medication for rUTI prophylaxis is intravesical therapy, whereby medication is instilled directly into the bladder using an in-out catheter. By targeting the site of the infection directly, this approach minimises systemic side effects and may be equally - or more - effective then oral antibiotics. However, it is an invasive procedure which needs to be administered by a trained healthcare professional.
Although the current evidence base for intravesical therapy is weak, a number of NHS hospitals have already started offering instillations of sterile solutions containing hyaluronic acid as treatment for rUTI. This is designed to temporarily replenish the natural protective lining of the bladder (the glycosaminoglycan (GAG) layer) to relieve the symptoms of UTI and strengthen the body’s ability to fight off infection. Another option, for which there is some signal of efficacy, may be to use an antibiotic for the intravesical treatment to directly challenge the pathogens causing the infection, without disturbing the gut microbiome as oral antibiotics can do.
The HTA Programme wishes to commission high-quality research to strengthen the existing evidence base regarding the clinical and cost effectiveness of intravesical therapies.
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 wish to submit a Stage 1 application for this call, the online application form can be found on the Funding opportunities page. To select this call, use the filters on the right of the screen or search using the call name and/or number.
Your application must be submitted online no later than 1pm, 29 March 2023. Applications will be considered by the HTA Funding Committee at its meeting in May 2023.
Guidance notes and supporting information for HTA Programme applications are available.
Important: 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 2023. 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 1 competing team. There may be unusual circumstances where the same person could be included on more than 1 application, e.g. a Lead from a named charity or a unique national expert in a condition.
For such exceptions, (i) each application needs to state the case as to why the same person is included, (ii) the shared Co-Applicant should not divulge application details between teams and (iii) 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 us: htacommissioning@nihr.ac.uk.