Develop the evidence base for Ear, Nose and Throat (ENT) medicine and surgery, ensuring new and current treatments in ENT are tested and evaluated so that patients can benefit from the best treatments in the field.

Proposed Research and Leadership Programme Figure 1 (below) presents a model of the translational pathway from fundamental and discovery science through both T1 and T2 ‘gaps’ and thence to implementation. Mapped onto this is a representation of UCL’s solution to these gaps, with specific reference to surgery. UCL is already leading the way in strategies to overcome the T1 translational gap, with high profile successes including first-in-man stem cell organ transplants in adults and children (Birchall, CBRC) and gene therapy for children with SCID (Thrasher, SBRC). The establishment of UCL Partners Academic Health Sciences System (MD Fish) has provided a comprehensive platform for the introduction of innovation into clinical practice - locally, nationally and internationally. However, a solution to the T2 gap causing a critical failure of continuity in the discovery to practice pipeline, specifically with respect to (surgical) translation, is still urgently required. Under the esteemed title of NIHR Research Professorship, the nominee aims to fit this final section into place. Key aim and approach The key aim of this 5 year programme is to establish a UK trials infrastructure which will support the development of a new cadre of research leaders – to transform the pipeline from ENT discovery to practices which benefit patients and populations. This programme will establish an evidence base for ENT and related specialties (specifically audiology, audiovestibular medicine, speech and language therapy), that will be readily applicable and applied in the NHS. The nominee will build a multidisciplinary trials group that will establish a robust pipeline and change culture for clinical trials in ENT and related specialties in the UK. This will form a worldwide reference centre for clinical trials in these disciplines. As a rapidly developing research leader, she will attract and train clinical researchers from across and outside the UK and thereby create the critical mass needed to establish a successful trials programme. Critically, this human resource will be the springboard for future trials and provide the leadership that will transform the quality and speed of translation from campus to clinic. With sustainably increasing revenue from NIHR, MRC and other sources and in close collaboration with the NIHR Clinical Research Network, it will be possible to build within the UK the world’s leading centre for ENT-related clinical trials within five years. Embedding this centre within UCL’s CTU and AHSS will ensure that it is designed, implemented and sustained aligning with the AHSS’ purpose - translating research and education into measurable health gain for patients and populations – in London, across the UK, and globally. Specific aims and strategies 2012-2017 a) Establish and strengthen collaborations and networks and identify priorities In order to build a sustainable infrastructure for trials and develop a research portfolio that will truly benefit population health, a network will be established with: representatives of patients, carers and the public (to generate ‘patient pull’), charities, health care and service (including education and commissioners) providers, research groups and networks, and food, pharma and technology industries. b) Design and implement structured electronic patient records and data systems for most common ENT diseases This is crucial not only in delivering better outcomes in health care (value; see Cii), but also in linking the huge potential of clinical cases treated within UCL Partners Trusts to trials (identifying patients that fulfil trial entry criteria) and research in general (prognostic research). The nominee has specific expertise in this area, as in her previous position at the UMCU Wilhelmina Children’s Hospital (fully paperless since 2009) her team has developed, in collaboration with ChipSoft and VitalHealth Software for Health 2.0, fully structured electronic patient care pathways and patient portals for children with upper respiratory disease and allergy [www.luchtwegportaal.com],and for children with hearing, speech and language problems. Both systems have served as a structure for clinical care as well as providing for a rich research database. Building upon the expertise within the UCL Partners IT Programme and the knowledge present in the associated Trusts, structured (patient accessible) EPR’s and data systems will initially be built for: children and adults with hearing loss and associated symptoms: ‘Open Ears’ analogous to ‘Open Eyes’ [http://www.openeyes.org.uk/index.html]; children with recurrent upper respiratory infections, and adult and paediatric laryngology patients.c) Value Central to the approach will be applying the principles of value [Porter M, NEJM, 2010] to trials and health care delivery: aiming to maximise useful outcomes for patients per pound spent on care. Trials will incorporate a novel, patient-centred approach to measuring Quality of Care including clinical quality metrics (outcomes where possible), patient reported outcomes (PROMS), and patient (PREMS) experience. The actual set of measures used in each trial will be co-selected up-front by multidisciplinary professionals whose expertise spans the whole pathway care, patient representatives and user groups in workshops. These workshops will review currently used/available measures, and triangulate this against what the patients and professionals believe would be the ideal set of measures encapsulating quality for each pathway and the practicalities of tracking each metric. Quality will be measured as above across a pathway, potentially spanning primary prevention to definitive treatment and recovery, as best fits the condition or clinical problem under consideration. Where possible quality measurement will be paired to actual cost of service provision, enabling to derive a measure of value in care delivery in the context of the trial. d) Enact priorities in clinical trials Examples of priorities identified so far are: -An RCT of Sound Field Amplification for children with glue ear Glue ear (OME) causes 90% of young children to suffer from episodes of hearing loss and difficulty understanding speech in noise. With evidence showing that the most common therapy, insertion of ventilation tubes, is only marginally beneficial, and the procedure listed as a low priority by the NHS, there is an urgent need for alternative strategies. Sound Field Amplification(SFA) is a technical solution to this which might give benefit to all children in a classroom and may reduce the need for remedial and special support. Building upon recent advances in SFA technology and work by Vickers (UCL Ear Institute) on the benefit each student may get from introducing SFA, an RCT will be designed to assess effectiveness in improving communication outcomes in classroom listening situations. -An RCT of proton pump inhibitors (PPI) and alginate in adults with laryngopharyngeal reflux (LPR) Symptoms of LPR comprise a significant proportion of the workload of ENT surgeons (up to 10% oftotal consultations with 61% of these patients requiring follow up appointments). Pragmatic nonevidence based treatment includes both PPI and alginates. Prescription of PPIs costs the NHS £300 million per annum. In collaboration with ENT surgeons from the University of Southampton (Kings, Frampton) a trial has been designed and ISRCTN registration has been applied for. -A feasibility study of Laryngeal Reinnervation versus Type I Thyroplasty in adults with Unilateral Vocal Fold Paralysis Patients (UVP) UVP, one of the most common conditions in laryngology, causes a weak and easily tired voice that compromises the quality of life as well as employment opportunities. There is surgical equipoise as to the most effective operation in this condition with the potential of laryngeal reinnervation to generate a better voice outcome in the long term. The nominee's group has recently web posted a survey across UK ENT surgeons exploring their treatment preferences and willingness to collaborate in an RCT. Before embarking on a full phase-3 trial, a feasibility study is proposed that will also serve as a test case for laryngological trials. NRES approval has been obtained and R&D approval is pending. -others potential studies include cochlear implantation in unilateral deafness (Saeed, UCL EI); freeradical scavengers in tinnitus (Davis, PD Centre for Hearing and Communication Evaluation, former MRC); vaccines (e.g. HPV, pneumococcus, NTHi) in upper respiratory disease in children (Birchall, Goldblatt UCL ICH, Sanders UMC Utrecht), communication and support programmes for elderly with deafness and dizziness and their carers (Davis), nasal septoplasty and FESS (with UMC St Radboud Nijmegen), ventilation tubes in recurrent AOM (with UMC Utrecht), screening and treatment of congenital CMV in newborns referred for hearing assessment after failing their neonatal screen (Davis and Carr, NHS Newborn Hearing Screening Programme). -regenerative medicine trials UCL regenerative surgery group (Birchall) leads the world in the T1 translation of stem cell- and cellbased tissue engineered organ replacements for airways and other head, neck and thoracic structures. A £1.2M MRC grant supports work which will lead to early phase clinical trials of partial laryngeal and tracheal replacement to commence in 2013. Other organ and tissue replacement solutions to unmet clinical needs will follow (nose, ear, oesophagus), and these bench-to-bedside trials are expected to generate a steady stream of phase III trials thereafter (linked to the new UK Cell Therapies TIC) The current proposal, including core funding for one feasibility study per annum, will provide the infrastructure and impetus for future full trials and is expected to realize a sustainably increasing revenue of funding from e.g. NIHR, MRC and other UK research councils, Wellcome Trust, Royal College of Surgeons, charities and industry. e.Biobanking The UCL/RFH Biobank has been established at the Royal FreeHospital (Lowdell, Director of Cellular Therapy & Biobanking). Technological advances make it possible to complete extensive analyses on small tissue samples. To this end, collecting and storing tissue, blood and secretions, now forms a crucial window into the understanding of ENT disease, and thus the development of new diagnostics and treatments. SOPS’s are in place covering recruitment, consent, safety, sample collection, storage and quality assurance for routine tissue-banking in ENT, and its related trials. f. Implementation and health service research The nominee will work closely with a range of experts (academics and practitioners) within UCL Partners and beyond in the design and implementation of the trials programme to ensure that it will facilitate translation to clinical practice in terms of its people (e.g. culture, networks), allocation of resources (e.g. prioritisation), and processes (e.g. knowledge transfer, dissemination mechanisms, guideline development). Fully integrated with the clinical trials programme, will be a series of implementation and health service projects, developed with international experts within UCL’s Faculty of Population Health Sciences: e.g. on healthcare inequalities, clinical desion making (Raine and Nazareth), and implementation and behaviour change related to surgical trials (Michie UCL, Blazeby and Donovan, Bristol). A study visit to Professor Grimshaw, University of Ottawa, the world’s leading expert in implementation and behaviour change is requested as part of this proposal. Through UCL and UCL Partners networks of practitioners already exist which can be harnessed to facilitate implementation. These will be strenghtened with a particular focus on clinical commissioners, and include such professional networks as, General Practice Research Framework and the Royal College of General Practitioners Clinical Innovation and Research Centre. Finally, UCLPartners has developed an effective model of implementation, which includes a number of evidence-based practices, including, e.g. patient and public involvement and outcome measurement. The nominee will work with the Directors within the UCLP core team to adapt and adopt this model to best suit her translational programme. LaySummary>