Development and evaluation of a complex ePrescribing-based Antimicrobial Stewardship (ePAMS+) intervention for hospitals: a mixed method study

Aims To develop, assess the feasibility and test the effectiveness and cost-effectiveness of a multifaceted ePrescribing-based Antimicrobial Stewardship intervention to safely reduce inappropriate antibiotic use in adult medical inpatient settings. Methods We undertook a mixed-methods programme of work organised into four interlinked work packages: Work package 1: (a) planning, developing and optimising all elements of ePrescribing-based Antimicrobial Stewardship; and (b) carrying out qualitative, feasibility and process studies of ePrescribing-based Antimicrobial Stewardship implementation. Work package 2: agreeing secondary outcome measures through an expert consensus building workshop, developing the methods to collect outcome data and establishing the feasibility of evaluating ePrescribing-based Antimicrobial Stewardship through a hybrid cluster-randomised stepped-wedge trial. Work package 3: evaluating the effectiveness of ePrescribing-based Antimicrobial Stewardship in achieving our coprimary outcomes of reducing antibiotic consumption without any adverse impact on 30-day mortality through piloting and undertaking a formal evaluation. Work package 4: estimating the cost-effectiveness of ePrescribing-based Antimicrobial Stewardship, including cost-minimisation and sensitivity analyses through evidence synthesis and expert engagement. Our research (which started on 1 January 2019) was majorly disrupted by the COVID-19 pandemic, with members of the team being redeployed to clinical and government advisory roles, and limited opportunities to undertake hospital fieldwork compounded by strikes. These delays resulted in our trial plans being pushed back by ≈ 3 years, by which time it was no longer possible to recruit sufficient numbers of hospitals into the planned definitive trial. Following discussion with the funders, we aborted plans to run the pilot and definitive trials, replacing this with qualitative scoping work to understand the ways in which trusts had innovated in the intervening period to promote antimicrobial stewardship (work package 5). Results We developed the ePrescribing-based Antimicrobial Stewardship intervention, comprising technical, educational and behavioural components and were able to agree secondary outcome measures and the cost-effectiveness model. The feasibility trial was undertaken in two hospitals in one trust, studying 24,884 antibiotic orders on 1958 admissions. This demonstrated that several aspects of the intervention were deliverable and that we were able to extract data on 20/43 outcome measures. Modelling of the coprimary outcomes, total antibiotic defined daily dose per admission, was feasible and enabled its variability to be estimated to support further research planning. There was, however, limited engagement of clinical staff with the training element of the intervention, which was initially only voluntary. Given the severe delays, many trusts had begun implementing their own approaches to deal with growing challenge of antimicrobial stewardship. As such, we were unable to find sufficient naive sites to progress the trial. Our additional qualitative scoping work identified the myriad ways in which trusts were attempting to respond to antimicrobial stewardship. These included order sets and order protocols, default durations, alerts for review, incorporation of guidelines, and audit and feedback functionality. Limitations We identify five key limitations: (1) the COVID-19 pandemic caused major delays, and non-COVID research activities had a lower priority than front-line clinical work and COVID-related research. The timescale for the development work is, therefore, unlikely to be representative of the time it should take to develop an intervention of this scope outside of pandemic contexts. (2) Although there was considerable stakeholder input into the development of ePrescribing-based Antimicrobial Stewardship, this did not include the entire potential user population. Nurses were under-represented. Although not directly involved in prescribing, more engagement with nurses would have been useful because they were involved in medication management workflows. (3) Undertaking the work in one trust limits generalisability, although inclusion of several ward types should help ensure that our findings related to a breadth of clinical contexts. (4) Implementation of ePrescribing-based Antimicrobial Stewardship within Cerner Millennium (North Kansas City, Missouri, USA) means feasibility in other systems still needs to be established. (5) The add-on study of antimicrobial stewardship practices included views of antimicrobial stewardship pharmacists and consultant microbiologists but did not include all hospitals nor ward prescribers. Nonetheless, this study provided many valuable insights into approaches, including the need for development of evidence for different practices. Conclusions We developed ePrescribing-based Antimicrobial Stewardship and conducted a feasibility trial of this in inpatient settings. This development and feasibility work was, however, undertaken during challenging circumstances resulting from a combination of the COVID-19 pandemic and National Health Service pressures, making it difficult for clinicians to fully engage. Delays with our work resulted in provisionally recruited trusts innovating in relation to antimicrobial stewardship such that it was no longer possible to deliver the planned follow-on pilot and definitive trials. In summary, ePrescribing-based Antimicrobial Stewardship is, in its present format, not suitable for use in National Health Service hospitals. Future work Hospitals are currently pursuing a range of approaches in an attempt to promote antimicrobial stewardship. There is a need to develop a typology of these approaches and establish the strength of the underpinning evidence using naturalistic designs. Trial registration This trial is registered as ISRCTN13429325. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0617-20009) and is published in full in Programme Grants for Applied Research ; Vol. 14, No. 12. See the NIHR Funding and Awards website for further award information.