Title: STEP DOWN: Stopping Treatment Excess in asthma, using linked Primary care Data and evaluating patient’s Opinions, across the Whole Nation
Funder: Department of Health and Social Care

Abstract: Research question What is the health impact of asthma overtreatment and how can we prevent it? Background Asthma is prevalent Around 1 in 13 UK adults are being treated for asthma. Nearly all patients, 96%, have their asthma managed by their GP; most have milder disease - 90% never or seldom have an asthma attack. Overtreatment is common Treatment mainstay is inhaled corticosteroids (ICS) and bronchodilators. 80-90% of maximal clinical benefit from ICS can be achieved with low-dose ICS. Asthma guidelines advocate stepping down to the minimally effective dose. Yet, over the past decade, asthma medication is prescribed at increasingly higher doses. Around 70% of patients on maintenance therapy use medium/high-dose ICS and remain on the same inhaler for years. Step-down occurs infrequently. Consequences of over-treatment:(1) Side-effects High-dose ICS has equivalent systemic absorption of oral corticosteroids. My systematic review assessing ICS side-effects in asthma, found an increased risk of pneumonia, fractures and cataracts. However, the few studies carried out had considerable limitations: Lack of power Inadequate follow-up Misclassification Considerable confoundingOther postulated side-effects, diabetes and cardiovascular disease, have yet to be evaluated. (2) Cost Stepping down suitable patients would save around 5% of the annual NHS asthma budget. ICS-containing drugs are the second most prescribed primary care medication 13% of the primary care drug budget is asthma medication(3) Medication burden There is a movement by GPs to rationalise medication. Notably, in asthma, once-daily are adhered to more than twice-daily inhalers.Why step-down is not happening Most primary care professionals lack confidence/are fearful of step-down find current guidelines unclear lack awareness of stepping down Guidelines are based on trial evidence - while evidence to step-up is strong, step-down evidence is deficient. Cochrane reviews found step-down trials have brevity of follow-up and small sample sizes. Only two trials (1997, 2003) were in primary care - both were small and not pragmatic trials. Biomarkers, proposed to aid step-down, Are not available in primary care Found to be no better than symptom-based led step-down Aims1) Measure the magnitude of common serious side-effects from asthma medication 2) Explore the barriers and facilitators for patients to stepping down 3) Carry out a feasibility study for a pragmatic RCT to test the hypothesis: 'Adults with well-controlled asthma can safely have their higher dose medication reduced within a primary care setting' Methods 1) Quantitative analysis: using >2.5 million electronic healthcare records from asthma patients, measure the risk of pneumonia, osteoporosis, fractures, cataracts, glaucoma, diabetes, bruising and cardiovascular events. 2) Mixed methods: survey and in-depth interviews of asthma patients 3) Feasibility study: assess the practicability of a step-down pragmatic RCT in primary care TimelinesQuantitative workstream: years 1-4 Mixed methods workstream: years 1-2.5 Feasibility study: years 2-3.5 Anticipated impact Understand the national scale of side-effects Educate professionals and patients Change guidelines to reduce morbidity increase NHS efficiency Ability to run a large pragmatic RCTDissemination Asthma UK/BLF (endorsed study): videos/leaflets/social media Primary Care Respiratory Society (endorsed study): newsletter/webinars/conferences British Thoracic Society (endorsed study): guidelines/conferences Scientific publications/conferences

Lay abstract: The problem Inhaled steroids were a breakthrough in asthma treatment and have saved many lives. However, using a large UK database of patient's medical records, I have found that adults with milder asthma are often prescribed higher doses than they need. As long-term higher dose inhaled steroids may cause several health problems, this means that the NHS is spending unnecessary money on expensive high-dose inhalers that may be causing harm to some patients. My objectives: Identify how common side effects are in adults using inhaled asthma medication Assess how to reduce asthma medication doses safelyBackgroundMost asthma patients are managed by GP practices, have milder asthma, and never, or seldom, suffer from asthma attacks. Nearly all the good effects from inhaled steroids can be achieved from a low dose. Asthma guidelines recommend that medication should be used at the lowest dose possible to maintain good control. Over the last 20 years, more and more patients have been prescribed higher doses of inhaled steroids (around 70%). Many patients could safely have their regular inhaled medication dose reduced, but this rarely happens; most are prescribed the same higher dose inhaled steroid for many years. Problems from overtreatment: More side-effects Only a few studies have assessed if inhaled steroids in asthma cause side-effects; they found an increase in chest infections, thin bones and cataracts. These studies had problems with how they obtained their findings. Better studies, with large amounts of patient data, are needed. Additionally, some suspected side-effects have never been looked at properly, including broken bones and diabetes. Higher NHS costs 13% of a GP's drug budget is spent on asthma medication. This is not surprising as inhaled steroids are the second most common GP prescription. Reducing medication doses in suitable asthma patients would save, every year, around 5% (34 million) of the total NHS asthma budget, allowing money to be re-directed to asthma services elsewhere. Medication burden Most patients do not wish to take higher medication doses than necessary. Current problem: There is a lack of scientific evidence on how to safely reduce asthma medication doses Doctors and nurses do not reduce higher medication doses as they find current guidelines unclearAims Find out how likely patients are to develop side-effects from asthma medication. Speak to patients about their views on reducing medication doses. Find out if it is possible to do a trial, which will test reducing higher dose medication in well-controlled patients seen by their GP.Design and methods Measuring side-effects: I will use medical records from 2.5 million unidentified adults with asthma to assess side-effects including chest infections, thin bones, eye problems, diabetes, bone fractures and skin bruising. Understanding patients' views: I will ask a larger number of patients to complete a survey, and speak to a smaller number in-depth, about their thoughts on reducing asthma treatment. Testing the feasibility of a future step-down trial: Longer term, I want to do a large trial in GP practices, but first I must show that this is possible. To do this I will: Measure GP & patient willingness to participate Find out how best to measure if reducing medication is safe Patient and public involvement41 patients and a retired practice nurse have helped me design this application. Their help was through discussion groups, a survey, participation in preparatory work and writing critique. Several members have volunteered for future roles (patient advisory group, study steering committee, writing and analysis groups). Communicating findings Animated videos and infographics through Asthma UK/British Lung Foundation, who support this study and have committed to disseminating findings Health media Scientific publications and talks

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RESPIRATORY