Title: Transforming treatment of fistula-in-ano : A novel bioresorbable Seton-scaffold device
Funder: Department of Health and Social Care

Abstract: Project plan: 1) Finalise design. -Finalise the design of the 'Seton-scaffold' device to satisfy the requirements for CE-mark registration following acquisition of clinical data. The proposed design is a 50-60mm x 3-4mm strip of scaffold based on the principle that one size will fit all fistulae. When folded longitudinally this will act as a 'Seton-scaffold' -Determine the optimum method of attachment to a fistula probe or to an existing seton and of securing the ends of the device together so that the product does not migrate or is uncomfortable for the patient. -Validated controlled manufacture and sterilisation process (including selection of a suitable packaging material) conforming to ISO13485 will be undertaken. 2) Development of insertion/fixation training model. -A verification/training model will be developed to teach the techniques of insertion/fixation and applicability to more complex fistulas. This will later become an essential training model during clinical phases of the project. 3) IP development. -Intellectual protection of this unique concept is acknowledged and a patent has been granted in Australia; applications are in progress in Europe, USA and Canada. The protected concept is the use of a biodegradable scaffold device which is held in in position within the FIA to prevent migration. There will be additional new material, design and process developments not specifically covered in our current protection; we will prepare and file new specific patent applications to protect these developments. 4) MHRA Regulatory approval. -The design dossier developed for the 'Seton-scaffold' product will be reviewed by a Notified Body as part of the CE mark application process towards the end of this project. Final classification as either a Class III or Class 2a medical device is expected. 5) Market assessment, business case and commercial strategy. -A detailed market assessment will include: potential market size, societal impact of FIA, clinical stakeholder input, peer review, risk assessment, regulation, patient feedback and health economic advantages. A multidisciplinary team will facilitate the development of the commercial strategy. -The economic assessment will involve the University of Birmingham Health Economics Unit. -The business case will include manufacturing costs, sales opportunity, selling price and cost comparisons with existing therapies. 6) NRES Ethics approval and Project Management. -Ethics approval will be obtained for First in Man (phase I) studies of safety and degradation as well as for patient and clinician acceptability. This study will also inform the need for modifications to the device, and allow development of training and assessment methodology for future clinical trials. Some indication of clinical efficacy may be obtained from the first-in-man study but verification via subsequent phase III multicentre RCTs will be needed (outside the remit of this current project). -Documentation, management of the programme, feedback to the funders and co-ordination of the three year plan will necessitate rigorous project management, which will be supported by the HTC and a dedicated project manager. Milestones and deliverables: Year 1: &bull; Finalised, sterilised and packaged prototype for testing &bull; Patent landscape mapped STOP/GO MILESTONE end of Year 1- have a finalised prototype device ready to enter approvals process and initial testing phase. Year 2: &bull; Regulatory approvals &bull; Market assessment: business plan, applicability STOP/GO MILESTONE end of Year 2 - have a device with regulatory approvals (CE mark) / Letter of No Objection from the MHRA; a robust business plan; clinical appetite for product Year 3: &bull; Post Market Clinical Follow Up Study / Clinical Investigation &bull; Safety and acceptability assessments FINAL MILESTONE end of Year 3- have a safe, clinically acceptable (to patients and clinicians) and commercially viable product ready for efficacy testing in a multicentre phase III trial.

Lay abstract: Background Fistula-in-ano (FIA) is an intrusive and embarrassing condition that affects around 12,000 new patients every year in the UK. Sufferers experience daily discomfort and smelly discharge from a tunnel connecting their back passage to their skin. The condition is notoriously difficult to treat and typically requires multiple operations under general anaesthetic, over several months or even years. These operations carry a risk of permanent anal incontinence, allowing uncontrolled emissions of gas and faecal soiling due to sphincter muscle damage. Despite this, failure rates are high, and some patients must live with FIA symptoms for the rest of their lives. Aims We aim to transform treatment of FIA by combining current management techniques with the latest materials technology. We propose the one-off placement of a therapeutic device, which may in some cases be utilised without a general anaesthetic. This will create a simple, cheap, safe and effective treatment which preserves continence, and avoids multiple sequential surgical procedures. If successful, it will be highly attractive to patients and health service providers globally. Design Over a three-year programme our experienced multidisciplinary team will work with patients and clinicians to finalise the design and then move forward into regulatory approvals, technique training and device production. By the end of the project we will have undertaken initial testing in patients. Patient and public involvement Patients with direct personal experience of FIA have been involved in this project since conception. This close collaborative partnership with patients will continue at every stage of the development of this device, with a named patient co-applicant on our programme management committee, and a patient focus group. Dissemination and future plans This project will produce a novel solution to treat FIA with a strong commercial appeal that is acceptable to both patients and clinicians, and is ready for clinical use.

Research activity codes: 6.3 MEDICAL DEVICES;5.3 MEDICAL DEVICES
Health categories: ORAL AND GASTROINTESTINAL