Title: Defining best Management for Adults with Chronic RhinOsinusitis: the MACRO Programme
Funder: Department of Health and Social Care

Abstract: Aims and Objectives: To establish best practice for Chronic Rhinosinusitis (CRS) management in adults across primary and secondary care. Background and Rationale: 11% of UK adults report CRS symptoms, with quality of life poorer than angina or chronic respiratory disease. 1% receive treatment from their GP each year, averaging 4 consultations annually. 40,000 sinus operations and 120,000 related outpatient consultations occurred in England and Wales in 2012-3. Recent European and UK guidelines emphasise limitations in current evidence. GPs often prescribe repeated antibiotic courses, contravening primary care guidelines. Evidence supporting longer-term antibiotic use in secondary care is incomplete and practice varies. Judicious use of antibiotics is essential to avoid resistance and side effects. Insufficient evidence defining the role of endoscopic sinus surgery (ESS) contributes to 5-fold variation in UK surgical rates. If surgery proves less effective than medical therapy, patients may be exposed to unnecessary risks, while if better, current delays reflect suboptimal care. Two 2014 Cochrane systematic reviews of CRS management concluded that studies are urgently needed. Research Plan: WS1: Understanding current management of patients with CRS and optimising trial design Routine data analysis: Linked national electronic health records (EHR) will identify current care pathways. Evaluation of different strategies will estimate the effectiveness of medical and surgical interventions, identify referral patterns and quantify rates of primary care consultation, hospitalisation, prescriptions (particularly antibiotic use) and surgical intervention. Health economic analysis: Cost-effectiveness analyses of treatments/pathways identified above will be conducted to inform the trial design in WS2 and identify deficiencies in anticipated data collection that could be focused upon for the trial-based health economic model. Qualitative analysis: Qualitative interviews with patients, GPs and ENT specialists will explore current attitudes towards treatment options and guidelines, including potential barriers. Interviews will explore the acceptability of 2 possible trial designs proposed for WS1, and consider recruitment, randomisation, retention, follow up and proposed outcome measures. WS1 will define current practice, estimate real world effectiveness of treatment pathways and inform trial design, including antibiotic choice and role of oral steroids. Consideration will be given to the proportion of patients with and without polyps and their natural history. Current uncertainty regarding management options necessitates pre-trial work to ensure relevance and acceptability of the trial and inform subsequent implementation programmes. WS1 will help ensure generalisability of trial outcomes and data linkage established will allow long-term outcomes to be captured, beyond the scope of the programme. WS2: Clinical trial to assess effectiveness of medical and surgical treatment Two possible designs are considered: A) 2-stage trial incorporating two linked randomised comparisons: antibiotic versus placebo for 3 months (stage 1); proceeding to randomisation to receive ESS or continued medical therapy for those without significant benefit (stage 2). B) 3-arm randomised trial patients comparing antibiotic or placebo or ESS. All patients will receive topical management with nasal corticosteroids and saline irrigation throughout in both designs. The target population is adult patients with CRS (European guidelines diagnosed). Primary outcome measure: 22-item Sinonasal Outcome Test (SNOT-22, a validated disease-specific quality of life instrument). Secondary outcome measures: endoscopic scores, SF12 and EQ-5D-5L questionnaires, adverse effects, surgical complications, costs and cost-effectiveness. 600 patients (16 UK centres) will ensure &ge;80% power to detect 10 points in the SNOT-22 (0.5SD, considered a moderate effect size), allowing for surgeon clustering and subgroup analysis (CRS with vs without polyps). A 6-month internal recruitment pilot, including a qualitative process evaluation on a sample of recruited patients and doctors, will ensure potential recruitment and retention problems are addressed. WS3: Establishment of best management and implementation Following completion and analysis of both workstreams, including detailed analysis of the clinical and cost-effectiveness of the interventions used, a full-day stakeholder consensus meeting will be convened to interpret the evidence generated, and ways in which this should be presented to patients, clinicians and commissioners. We will produce structured management guidelines for use across the NHS. We will recommend subsequent implementation strategies. EHR data linkage of consenting trial participants will allow long-term follow-up. Projected outputs and dissemination plans: Team members already engaged with key organisations in guideline development will actively share results through primary and secondary care networks and the public domain. PPI panel will ensure findings are presented in an accessible and relevant way for patients. Sharing EHR-linked models with CCGs will assist in implementing changes in routine practice and monitoring healthcare utilisation to evaluate impact. Utilising links with CLAHRCs and AHSNs we aim to initiate knowledge transfer and clinical implementation programmes, which, although beyond the scope of this programme, are essential to maximise its benefit. Benefits to patients and the NHS: Stronger treatment recommendations will standardise practice, ensuring judicious use of antibiotics (minimising risks of resistance) and surgery, while reducing the impact of CRS on quality of life and productivity. Given its prevalence, this could have substantial economic benefits for the NHS.

Lay abstract: More than 1 in 10 UK adults report symptoms of Chronic Rhinosinusitis (CRS), which include a blocked and runny nose, loss of smell, facial pain, tiredness and breathing problems, such as asthma, being worse. Studies have shown a greater impact on quality of life than heart disease and back pain. Each year more than 600,000 adults are treated for CRS by their GPs. They attend an average of four appointments per year and are prescribed a variety of different drugs; 91% receive antibiotics, often with repeated courses. Over 120,000 attend hospital each year, with around 40,000 subsequently undergoing surgery, having experienced insufficient improvement from medication. However, current guidance for all these treatments is limited since the evidence on which it is based is weak. Our team, with help from patients and the public, has developed a programme of research to establish which treatments work best for adults with CRS and to ensure they are adopted as best practice by GPs and hospital doctors. Our team includes GPs, experts in sinus disease and breathing disorders, research experts and patient representatives, from across the UK. We propose 3 closely linked workstreams to address the research objectives: Workstream 1: Analyse information routinely collected in the health records of patients with CRS to establish what treatments they currently receive from GPs and in NHS hospitals, estimating how effective these are in terms of further healthcare visits and treatments, and how much they cost. Through interviews, establish patients and doctors attitudes towards current treatment options, and explore the design of the trial below. Use this information to determine the ideal study to establish the best treatment for adult CRS patients. Workstream 2: Perform the clinical trial determined to be most relevant, comparing longer-term antibiotics, placebo (blank drug) and surgery simultaneously or in 2 stages; either comparing longer-term antibiotics with placebo, and then comparing surgery with continuing medical treatment, or comparing the three options in parallel. All patients will receive nasal steroids and saline rinses throughout since previous studies have shown them to be effective. It will include 600 adult CRS patients across 16 hospitals, with patient-rated symptom scores as the main outcome. Workstream 3: Analyse and interpret the results of the first two workstreams, using a variety of techniques, to enable the team to recommend the best pathway for treating people with CRS, to design the best approach to make sure that doctors are familiar with and use that pathway, and to effectively inform patients of the recommendations. Overall, this research, conducted over 7 years, will define the most effective treatments for CRS patients within the NHS, minimizing the impact of disease, and reducing practice variation and ineffective use of healthcare resources, including inappropriate antibiotics.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: INFECTION