Title: Safety of reducing antibiotic prescribing in primary care. New evidence from electronic health records
Funder: Department of Health and Social Care

Abstract: Background: Many antibiotic (AB) prescriptions in primary care are unnecessary and the NHS is now incentivising reduced AB prescribing. If AB use is reduced too much, this might carry risks to patient safety if bacterial infections and their complications increase. Very few studies have evaluated this possibility. Objectives: This research asks whether it is safe to reduce AB prescribing in primary care? Is there a risk that bacterial infections might be more frequent if ABs are prescribed less often? If so, what is the safest way for the NHS to promote reduction of AB prescribing in primary care? Methods: There will be three work packages (WP): WP 1: Epidemiological Study. We will systematically identify a comprehensive list of safety outcomes relevant to a policy to reduce overall AB utilisation in primary care. Case definitions will be developed. A cohort study will be conducted using electronic health records (EHRs) from the Clinical Practice Research Datalink (CPRD) with linked hospital episode, mortality and deprivation data. At population- (general practice-) level, we will estimate the incidence of each safety outcome by level of AB prescribing. At individual-level, we will conduct a series of epidemiological studies to evaluate relative and absolute risks of safety outcomes, allowing for confounding by indication using appropriate epidemiological methods. We will obtain estimates for the primary care population stratified by age-group, gender, comorbidity status, smoking, deprivation and, in older adults, frailty level using e-Frailty index. WP2: Modelling Study. There are trade-offs involved in reducing AB use. Benefits from reduced AB prescribing may be accompanied by small increases in risks to safety. In order to make these trade-offs explicit, we will construct a simulation model. Incidence estimates from EHR analyses will inform the model of the risks of infectious complications by pre-specified population sub-groups. The model will enable estimation of changes in numbers of safety outcomes per unit change in AB utilisation, contrasting universal versus targeted strategies for AB reduction. WP3: Translational Study: This will comprise two elements. An informatics stream will develop practice profiles of AB prescribing indicators and embed these into practice systems. There will also be a qualitative interview study to explore how patients, prescribers and managers understand and respond to the research evidence from WP1 and WP2. What are their values and preferences with respect to safety issues in the context of AB prescribing? The qualitative study will directly inform research in the informatics stream. Patient and public involvement: The idea for the study has been discussed with patients one of whom will join the study team as a co-applicant. A PPI group will meet quarterly to discuss and provide advice on the conduct of the study. Dissemination: We will prepare a report and evidence summaries to communicate our results to patients and policy makers at the Department of Health, National Institute for Health and Clinical Excellence, Public Health England and the NHS

Lay abstract: It is known that infections are becoming more resistant to treatment by antibiotics (ABs). This could be because ABs are being prescribed too frequently. Therefore, we need to make sure that ABs are only prescribed when they are really needed. In the UK, about 70% of ABs are prescribed by GPs in primary care. Around 60% of all ABs prescribed by GPs are to treat cough, colds, sore throats etc, often called Respiratory Tract Infections or RTIs. Skin infections and urinary tract infections account for most other AB prescriptions. Not all infections need AB treatment. For example, most RTIs will get better without requiring ABs, but despite this, ABs are prescribed in roughly 50% of cases. This may be because doctors and patients are concerned about the risk of not treating an apparently minor infection. We currently don’t know what level of AB use in primary care is acceptable and safe. Our recent study, which was published in the British Medical Journal, found that more serious infections such as pneumonia and peritonsillar abscess (usually known as quinsy) may be a little higher in general practices that prescribe fewer ABs. This research is to understand more about the safety of reducing AB prescription in primary care, and to understand the impact of policies aimed at reducing AB prescribing. We will compile a full list of possible infection complications and relevant patient outcomes if such a policy was adopted. We will then study primary care patient electronic health records to find out if the risk of each outcome is greater when ABs are not prescribed. We will also analyse Hospital Episode and mortality statistics. The data will be analysed in several different ways. We will look at it from an individual patient perspective and also across general practices. We want to identify those groups where risk of each infection complication is greatest. This will include sub-groups of age, gender, associated health conditions, and in very old people, according to their level of frailty using an established frailty measure. We will use these results to create a simulation model. This will enable us to model the impact on safety outcomes, and the costs, of reducing AB prescribing by different amounts in different population groups. In the next stage of the research, we will talk to patients, health practitioners and managers about our findings. We will develop a profile of AB prescribing indicators. We will work with informatics specialists to find out whether the proposed new AB prescribing indicators can be implemented into general practice computer systems, and whether these will provide managers, clinicians and patients with information they can use to reduce AB prescribing safely. The idea for the study has been discussed with patients one of whom will join the study team as a co-applicant. We will have a patient advisory group that will meet regularly and advise the research of the views and values of patients. This research will provide policy-makers with better evidence concerning the safety of policies to reduce AB prescribing. The research will also help to inform the decisions of individual patients and health practitioners about whether ABs need to be prescribed across a wide-range of clinical contexts.

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