Title: Developing and testing a framework for evaluating interventions targeting antimicrobial resistance
Funder: Department of Health and Social Care

Abstract: BackgroundAntimicrobial resistance is a serious public health problem and a global threat, with an estimated 10 million people expected to die of drug resistant infections every year by 2050. (1) The spread of resistant bacteria in healthcare settings is a major issue for patient safety. Antimicrobial resistance (AMR) is fuelled by the inappropriate use and prescribing of antibiotics, of which over 80% are prescribed in primary care in the UK. A recent report showed that nationally, antibiotic prescribing is increasing each year, the majority of prescribing is coming from primary care and areas with higher prescribing often have higher levels of AMR. (2) In the UK interventions with the aim of reducing antibiotic prescribing in primary care have been initiated at the local, regional and national level, and have recorded varying degrees of effectiveness. (3-5) Interventions to examine issues of major public health concern, such as AMR are frequently developed in response to a heightened public awareness and mounting pressure to deliver solutions. Under these circumstances, a groundswell of public and professional opinion may prompt the introduction of specific interventions to target the problem, even as local measures are employed. Insofar as these various interventions are effective, they produce a positive rising tide' of effect that is unlikely to be the result of one intervention or a top layer policy change, but may be mediated by many changes at the organisational level. (6) The overall aim of this research is to develop a framework for evaluating interventions targeting AMR, focusing on interventions recently introduced to at the policy level to reduce antibiotic prescribing in primary care in the UK. The framework will use routinely collected clinical data and will comprise of a series of methods for evaluating such interventions. This research addresses repeated calls from the Department of Health, the NIHR and MRC to utilise routinely collected data to evaluate clinical and public health interventions for the NHS. (18) Planned research The framework will comprise of methodologies using routinely collected clinical data to compare prescribing and microbiology data pre and post intervention and examine causality in evaluating interventions to reduce antibiotic prescribing in primary care. Application of the framework will address the following, in three separate studies: Do policy level interventions have an effect on antibiotic prescribing? What interventions are used at a local level and how do these mediate effects of policy interventions on antibiotic prescribing? Do policy and local level interventions have an effect on AMR? The three studies will use the following approach: A natural experiment, using time-series analysis to evaluate the effect of policy interventions on antibiotic prescribing. A spatial map of changes will be generated to examine geographical variation in effect A systems modelling approach will be used to assess causality of effects, including a mediation analysis An ecological study will examine the effect of interventions on AMR rates and a combination of multilevel and mathematical models will be used to quantify the effect of interventions on AMR in both the community and hospital settings Relevance to the NHS and patients Robust evaluation of AMR interventions will provide policy-makers with the evidence they need to effectively implement relevant public health policies. An understanding of the effectiveness of this policy, the mechanisms and mediators of its effectiveness and the consequences of interventions on AMR will be important for further refinement of interventions. Developing methods using routinely available data sources will allow monitoring over time. Ultimately, application of evaluated, evidence based interventions, targeting antibiotic prescribing in the primary care setting, will lead to more appropriate antibiotic prescribing for patients.

Lay abstract: Antibiotics (as part of a group of drugs called antimicrobials') are important medicines for treating bacterial infections in both humans and animals. However, many bacteria are able to adapt and find ways to survive the effects of an antibiotic. This means antibiotics are losing their effectiveness and, the more we use antibiotics, the greater the risk that they will no longer be used to treat infections in future. Antimicrobial resistance (AMR) is one of the most significant threats to patient safety in Europe. It is driven by overusing antibiotics and prescribing them inappropriately. Here in the UK, healthcare provided by GPs which is often termed primary care - is responsible for almost 80% of all antibiotics prescribed. A recent report showed that, nationally, this antibiotic prescribing is increasing each year and that areas with higher prescribing have higher levels of AMR. There are currently many different initiatives which aim to lower unnecessary antibiotic prescribing in primary care in an effort to reduce the threat of antimicrobial resistance. Finding out which initiatives work - and how they work - is crucial for identifying which have the best chance of success in reducing inappropriate prescribing and addressing the problem of AMR. As with many important public health issues, there is heightened pressure on policy makers and healthcare providers to tackle the issue of AMR rapidly be that at a local, regional or national level. This means that many of initiatives get introduced in an unplanned manner, with no formal method for assessing how effective they are. In turn, this can make it difficult to pinpoint which particular strategy is responsible for particular changes. For example, it may be that one strategy works better in one part of the country than another. Understanding what works and why it works is essential if policy-makers, commissioners, researchers and clinicians are to pinpoint the most useful initiatives to reduce AMR. I plan to use a variety of methods for assessing the effectiveness of initiatives to reduce antibiotic prescribing in primary care. These methods will provide a framework which can be used nationally by the NHS, to evaluate initiatives to tackle AMR on a long-term, sustainable basis. I will then test this framework in a real-world scenario by using it to evaluate an existing strategy to reduce antibiotic prescribing in primary care. In 2013, the UK Department of Health introduced new policy guidelines for antibiotic use in primary care, aiming to bring about a reduction in antibiotic prescribing. Using the various methods proposed in the newly-designed framework, I will fully evaluate this policy-level change. I will use the framework to map the initiatives that are used at a local level i.e. by Clinical Commissioning Groups (CCG) - to determine how these local initiatives can work alongside top level policy changes to affect antibiotic prescribing. Finally, using the framework alongside routinely collected surveillance data, I will produce a mathematical model to measure the extent to which AMR in hospitals is influenced by primary care and how this relationship is affected by initiatives to reduce antibiotic prescribing in primary care.A comprehensive plan for sharing research findings has been developed, which includes local, regional and national commissioners within the UK, EU policy makers and a public workshop where we will present our framework and demonstrate the benefits of using routinely collected clinical data to shape future healthcare policy and practice.

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