Title: Development and evaluation of a complex ePrescribing-based Antimicrobial Stewardship (ePAMS+) intervention for hospitals.
Funder: Department of Health and Social Care

Abstract: Aims To develop and evaluate a multifaceted intervention (ePAMS+) that incorporates technical, behavioural and organisational components to safely reduce inappropriate antibiotic use in adult medical in-patients. Questions What are the main challenges to and facilitators for reducing inappropriate antibiotic use? (WP1) In what ways can ePAMS+ promote antimicrobial stewardship (AMS)? (WP1) How is ePAMS+ best conceptualised/delivered? (WPs1&2) What are suitable secondary outcomes and process measures? (WPs1&2) Is ePAMS+ acceptable/feasible to implement? (WP2) Are our trial procedures acceptable/feasible? (WP2) How much patient-level variability is there in the co-primary outcomes? (WP2) Is ePAMS+ effective in safely reducing inappropriate antibiotic use? (WP3) What are the mechanisms of action/unintended consequences of ePAMS+? (WPs1-3) Is ePAMS+ cost-effective? (WP4) Background/rationale Despite national guidance, antibiotic prescribing rates are still increasing in hospitals. The reasons are multi-factorial, including limited real-time access to information that may influence decisions to initiate antibiotics, concerns about missing potentially serious infection (e.g. sepsis), and lack of continuity of care, which limits the opportunity for an informed review of progress and results in a reluctance to delay initiation of and/or change/discontinue an antibiotic that has already been commenced. These challenges are compounded by the substantial time pressures that clinicians face. The national strategy to address issues surrounding AMS is to encourage clinicians to &ldquo;Start Smart&ndash;Then Focus&rdquo;. Our systematic review and discussions with experts all point to ePrescribing systems&ndash;integrated with behavioural and organisational support&ndash;having a major role in improving AMS. We have carefully conceptualised a complex ePrescribing-based Antimicrobial Stewardship (ePAMS+) intervention that aligns with national strategy and aims to help busy clinicians overcome a number of the above-described challenges. Research plans We will undertake a mixed-methods programme that comprises four inter-linked Work Packages (WPs): WP1: a) Planning, developing and optimising all elements of ePAMS+; and b) carrying out qualitative feasibility and process studies of ePAMS+ implementation in parallel with WPs2&3. WP2: Agreeing secondary outcome measures through an expert consensus building workshop, developing the methods to collect outcome data and establishing the feasibility of evaluating ePAMS+ through a hybrid cluster-randomised stepped-wedge trial. ePAMS+ and our trial plans will be reviewed in the light of the findings from this feasibility work. WP3: Evaluating the effectiveness of ePAMS+ in achieving our co-primary outcomes of reducing antibiotic consumption without any adverse impact on 30-day mortality through piloting and undertaking a formal evaluation in 10 hospitals. Our secondary outcome measures will include additional important safety and process outcomes based on the consensus building exercise and feasibility work undertaken in WP2. WP4: Estimating the cost-effectiveness of ePAMS+, including cost-minimisation and sensitivity analyses. Outputs/dissemination plans If found to be acceptable, safe and cost-effective, we will incorporate ePAMS+ into our existing national ePrescribing Toolkit to maximise dissemination throughout NHS England. We anticipate publishing at least 10 papers in leading journals. Benefits Reducing the risk of antimicrobial resistance is a major national and global challenge. Our programme of research will make a substantial contribution to this effort through leveraging the increasing technological capability in hospitals to promote AMS in a safe and cost-effective manner.

Lay abstract: Increasingly, bacteria (germs) no longer respond to antibiotics. This means antibiotics have begun to stop working as well as they should. This can result in patients experiencing more severe infections, lasting longer than they previously did, and may, in some cases, lead to an increased risk of dying from infections. This is due to too much inappropriate use of antibiotics. The UK Government and World Health Organization believe this is an extremely important issue to tackle. To improve antibiotic prescribing, &quot;6Rs&quot; should be followed; patients should be given: the Right antibiotic; at the Right dose; by the Right route; for the Right infection; at the Right time; and for the Right duration. The reasons for overuse of antibiotics include doctors not having relevant information (e.g. on resistance patterns) when prescribing antibiotics, concerns about missing possibly serious infections, and time pressures/lack of continuity of care, limiting opportunities for doctors to review diagnoses and stop antibiotics if no longer needed. Our literature review and discussions with experts found that hospital electronic prescribing (ePrescribing) systems can be used as a type of software that can be used to support new ways of working designed to safely reduce inappropriate antibiotic prescribing. Most of this work however comes from the United States. There is very little UK experience of developing such interventions to achieve the 6Rs. We will build on our recently completed NIHR-funded research, which developed an ePrescribing Toolkit (http://www.eprescribingtoolkit.com). This has promoted the use of hospital ePrescribing systems across NHS England. As ePrescribing systems become more widely available, we want to see if they can be used to safely reduce antibiotic prescribing with no change in mortality. We will begin by carefully planning all the elements a new intervention (ePAMS+) needs to help hospitals achieve the 6R's. From our preliminary work, we anticipate that ePAMS+ will incorporate two closely related parts: i) a training package, clinical team processes and patient leaflet to help everyone involved understand the importance of reducing antibiotic use and how this can be done safely and effectively; ii) an online computer software system that works with the existing ePrescribing system, gathering information relevant to making antibiotic prescribing decisions, presenting this to clinicians at the time and in the format it is needed, and monitoring/providing feedback to clinical teams on the appropriateness of their antibiotic use. We will investigate how best to deliver ePAMS+ to hospitals by testing it on a small scale before undertaking a larger study. This will allow us to measure the clinical effects of ePAMS+ on antibiotic use and assess whether ePAMS+ is a good use of NHS resources. We will do this by comparing antibiotic prescribing/administration before and after introducing ePAMS+.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: INFECTION