Approaches to promoting the appropriate use of antibiotics through hospital electronic prescribing systems: a scoping review

Keywords: antimicrobial resistance, health information technology, review

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AbstractObjective: To identify approaches of using stand-alone and more integrated hospital ePrescribing systems to promote and support the appropriate use of antibiotics and identify gaps in order to inform future efforts in this area.

Methods: A systematic scoping review of the empirical literature from 1997 until 2015, searching the following databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Google Scholar, Clinical Trials, International Standard Randomised Controlled Trial Number Registry, Economic Evaluation database, and International Prospective Register of Systematic Reviews. Search terms related to different components of systems, hospital settings and antimicrobial stewardship. Two reviewers independently screened papers and mutually agreed papers for inclusion. We undertook an interpretive synthesis.

Key findings: We identified 143 papers. The majority of these were single-centre observational studies from North American settings with a wide range of system functionalities. Most evidence related to computerised decision support (CDS) and computerised physician order entry (CPOE) functionalities, of which many were extensively customised. We also found some limited work surrounding integration with laboratory results, pharmacy systems, and organisational surveillance. Outcomes examined included healthcare professional performance, patient outcomes and health economic evaluations. We found at times conflicting conclusions surrounding effectiveness, which may be due to heterogeneity of populations, technologies and outcomes studied. We failed to identify any reports of unintended consequences.

Conclusions: Interventions are centred on CPOE and CDS, but also include additional functionality aiming to support various facets of the medicines management process. Wider organisational dimensions appear important to supporting adoption. Evaluations should consider processes, clinical, economic and safety outcomes in order to generate generalisable insights into safety, effectiveness and cost-effectiveness.

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IntroductionAntimicrobial resistance has emerged as one of the most pressing problems of the 21st Century. 1

The threat of antimicrobial resistance is greatly exacerbated by inappropriate antibiotic use, which increases the emergence of resistant bacterial strains.2 Maximising the effectiveness of existing antibiotic treatments through resources that facilitate optimal use in humans is one key approach to mitigating the risks of antimicrobial resistance.3

The focus on promoting the appropriate use of antibiotics in hospital settings is based around organisational approaches to promoting and monitoring the judicious use of antimicrobials to preserve their future effectiveness.4 There is increasing evidence to suggest that antimicrobials are commonly prescribed inappropriately in hospitals. For example with treatment regimens continued for longer than is necessary and prescribing for non-bacterial infections,5-7 both of which can promote antimicrobial resistance.

In response to this, many governments are now supporting the development of guidance, intended to support clinicians to more appropriately initiate and maintain antibiotic use.8 ePrescribing systems can potentially offer considerable support for many aspects of the appropriate use of antibiotics in hospitals,9 and the existing evidence from other areas shows that computerised physician order entry (CPOE) and computerised decision support (CDS) systems in particular may offer significant potential.10-12

With ePrescribing systems increasingly being embedded within hospital information technology infrastructures and clinical workflows, an opportunity therefore exists to develop interventions that support all key decisions within the antibiotic prescribing process, but there is currently uncertainty as to how these interventions are optimally conceptualised and deployed.13 Existing evidence surrounding CPOE/CDS interventions targeted at individual prescribers from other areas may have limited applicability to the area of antibiotic stewardship (AMS),10-12 and does also not provide insights into wider social and organisational transformations that need to accompany a program of this sort (e.g. the role of clinical pharmacists).14

In order to address this gap, we conducted a systematic scoping review of the literature to identify and describe existing and emerging approaches to promoting the appropriate use of antibiotics through hospital ePrescribing systems. In doing so, we were particularly interested in identifying potential approaches to improve the appropriate use of antibiotics beyond interventions targeting individual prescribers.

Methods

Search strategyWe searched the published empirical literature from 1997 until September 2015 for work investigating the use of ePrescribing and associated health information technology systems to improve the appropriate use of antibiotics. The start date was chosen due to published guidelines from the Society for Healthcare Epidemiology of America and Infectious Diseases Society of America that year, emphasising the importance of appropriate use of antibiotics to prevent antimicrobial resistance in hospitals.3

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Databases in this search included: MEDLINE, EMBASE, and The Cochrane Database of Systematic Reviews. We also electronically searched Clinical Trials (https://clinicaltrials.gov/), the International Standard Randomised Controlled Trial Number (ISRCT) Registry (www.isrctn.com/), the Economic Evaluation database (http://www.crd.york.ac.uk/CRDWeb//), and the International Prospective Register of Systematic Reviews (www.crd.york.ac.uk/PROSPERO/) for work in progress. We used the search engine Google Scholar to identify additional potentially eligible studies.

Search terms related to different components of ePrescribing systems, hospital settings and terms surrounding the appropriate use of antibiotics. We searched titles and abstracts as well as subject headings (see Appendix 1). More specifically, terms in the first group were based on a search strategy we employed previously in a systematic review of the eHealth literature, focusing on functionality commonly associated with ePrescribing systems.15 The search terms in the second group related to the appropriate use of antibiotics, drawing on a review of published studies underlying the guidelines developed by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America for developing an institutional programme to enhance AMS and existing Cochrane reviews.13 The search terms in the third group related to the hospital setting, as interventions from primary care may not easily be transferable to hospital contexts.

Terms within groups were combined using the Boolean operator “OR” and sets were combined with the Boolean operator “AND”. We applied English language restrictions and used no methodological filters.

Inclusion and exclusion criteriaWe included experimental studies of various designs that examined the effect of ePrescribing systems on the appropriate use of antibiotics in hospital settings.

Studies were excluded if they fell outside our scope of interest, for example if they: Did not relate to both ePrescribing functionality and the appropriate use of antibiotics Evaluated technology that is not commonly associated with core ePrescribing functionality Focused on the implementation of technology in primary care settings due to different

contextual circumstances Did not include experimental designs Focused on the implementation of systems in low-income countries (defined as having a

gross national income per capita lower than US$ 4,036) due to different contextual circumstances 16

Two reviewers independently screened articles for inclusion, discussed these and resolved discrepancies.

Data abstraction and synthesisTwo researchers independently undertook data abstraction from each study. Data were abstracted onto a customised data extraction sheet. Variables included: author and year; title of the study; country of origin; design; hospital setting/specialty; system functionality/intervention; evidence for impact on practitioner performance; evidence for impact on patient outcomes; evidence on cost-effectiveness; conclusions; and potential applicability to UK NHS hospitals. Key findings from each

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study were summarised and presented in tables. Reviewers coded the variables and resolved any disputes through mutual discussion.

We followed three main steps in conducting an interpretive synthesis of our findings:17 (1) noting the range of functions and uses of ePrescribing and related systems to promote/improve antimicrobial stewardship; (2) developing a synthesis of the findings of included studies; (3) and exploring relationships in the findings.

ResultsWe screened titles and abstracts of 3471 papers, and full texts of 421 references. 143 papers were selected for inclusion (see Figure 1 and Appendix 2).18 Of these, 121 were observational studies, nine systematic reviews, five surveys, and three randomised controlled trials (RCT). Only a small number of studies (n= 5) included a qualitative component. The majority of papers originated from North American settings (n=87), followed by Australia (n=11), the UK (n=10), France (n=5), Canada (n=5), Israel (n=4), Germany (n=4), South Korea (n=3), Denmark (n=3), the Netherlands (n=3), and Singapore (n=2). One study each originated from Belgium, the Czech Republic, Portugal, Spain, Switzerland, and Taiwan.

System functionalities – a focus on improving individual performance in specific clinical settingsMost evidence came from specialty settings (such as intensive care, emergency medicine, and paediatrics);19-72 and from high risk patient groups (e.g. those at risk for or with infections);58, 73-80 and from tertiary care.26, 50, 66, 67, 69, 81-96

We found that most work has been conducted in relation to CPOE and CDS systems, focusing on interventions that targeted individual prescribers through prompts and reminders. 21-26, 28, 31-34, 36, 37, 39-

50, 53-62, 64, 65, 67, 68, 71, 73, 76-80, 82-86, 88, 90, 91, 94, 96-138

The majority of systems were “home-grown” standalone systems, implemented in single centres, and extensively customised; but we also identified some work on packaged applications.21, 52, 53, 74, 96,

110, 138-141 Research activity surrounding more complex and distributed functionalities that integrated ePrescribing with medical notes, pharmacy systems and laboratory results was less common.29, 30, 39,

40, 48, 52, 53, 58, 61, 63, 76, 77, 81, 87, 89, 116, 120, 124, 139, 141-144

Overall, system functionalities varied significantly across studies, making comparisons difficult.

Outcomes investigated - from practitioner performance to patient outcomes and costWe found that the majority of ePrescribing interventions to promote the appropriate use of antibiotics examined healthcare professional performance, followed by patient outcomes and cost assessments (see Box 1). These were often measured in isolation with little effort to assess relationships between them.

In relation to practitioner performance, the studies reported improved turnaround time for first dose of antibiotic,19, 23, 25, 30, 34, 43, 48, 52, 55, 57, 64, 67-69, 73, 82, 86, 90, 94, 106, 124, 129, 131, 133, 134, 145, 146 improved selection of antibiotics (e.g. in line with local protocols),22, 25, 27, 28, 35, 37, 38, 54, 55, 58, 59, 62, 64-66, 68, 70, 71, 76, 77, 90, 92, 95, 101, 108, 112, 115,

117, 122, 129, 131, 134, 135, 147, 148 optimal dosing,31, 39, 41, 43, 44, 55, 69, 79, 80, 87, 95, 107, 125, 126, 149 improved adherence to guidelines/protocols,20, 21, 24-26, 36, 37, 45, 56, 60, 64, 65, 71, 78, 83, 85, 92, 93, 95, 101-103, 105, 127, 133, 142, 150 and a decrease in the

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total number of antibiotics prescribed.26, 49, 61, 66, 92, 95, 96, 119, 129, 132, 150-153 Some studies also reported a reduction in prescribing errors and increased de-escalation,23, 33, 42, 49, 66, 91, 94, 100, 113, 114, 126, 128, 138, 139, 146, 154,

155 as well as improved antibiotic sensitivity and increase in sensitivity of surgical site infection detection.26, 39, 51, 75, 143, 156, 157 Others reported a timelier discontinuation of antibiotics and a decrease in the meantime to antibiotic administration.45, 49, 53, 87, 88, 116, 119, 120, 140 One study suggested that systems could help to identify prescribers who performed best and those with suboptimal performance.109

Examining patient outcomes was less common, but the most frequently reported measures included adverse drug events, 39, 46, 49, 76, 80, 111, 129, 135, 136, 158, 159 mortality,56, 76, 99, 118, 135, 141, 144 and length of hospital stay associated with antibiotics.39, 61, 76, 97, 99, 129, 135 We also found some work relating to examination of rates of post-operative wound infection,78, 129, 134, 154 the emergence of drug-resistant pathogens,115, 135

susceptibility relating to certain classes of antibiotics,72 and reduced rates of drug hypersensitivity reactions.158

Cost-effectiveness was least frequently examined, although some studies indicated cost savings relating to total antibiotic expenditure,19, 29, 39, 49, 87, 120, 122, 129, 132, 135, 141, 144, 151 and cost of hospitalisation.39,

44, 97, 129, 139, 151 Others measured costs relating to future resistance 76 and overall pharmacy interventions.102

Embedding systems within their social context of use – from individual performance to social transformationsSome studies indicated a lack of impact of systems in relation to practitioner performance,32, 40, 47, 81,

104, 152 and patient outcomes.19, 26, 27, 46, 50, 61, 67, 70, 98, 101, 121, 122, 129, 136, 137, 160, 161 One study reported worse patient outcomes after implementation of an electronic allergy label.162 Similar issues emerged when considering costs. Two studies concluded that systems did not result in significant cost savings,25, 115

whilst some studies showed an increase in costs, even though the quality of prescribing was better. 98,

99, 101 This was mainly due to the fact that although the use of some antibiotics (e.g. restricted antibiotics) rose, the overall cost was reduced (due to a decrease in the use of other types).

These conflicting findings appeared to be due to social contexts in which systems were used and deployed. Here, interventions may in some instances lead to unintended consequences that are difficult to anticipate. For example, some system recommendations were rejected as clinicians deemed them inappropriate,84, 91, 104, 144, 160 some expressed difficulty in complying with local guidelines so that the system made no difference to their antibiotic prescribing practices, 163 and others reported changes in workflows as potential contributory factors.138 This was particularly true for complex cases.83 Studies also indicated that systems may adversely impact on user time. Whilst some authors reported time-savings, others reported time-increases for clinical users.57, 63, 64, 67-69, 94, 124,

129, 131, 133, 134, 145

These issues may, to some degree, be addressed by increasing system usability;130 and ensuring that interventions are deployed as part of wider organisational transformations, paying attention to the variety of contexts in which they are used.20, 27, 50, 52, 85, 120, 141

Secondary uses and medication management processesThere was limited evidence surrounding interventions that had a broader organisational focus and those that investigated approaches to re-using data held within systems.29, 30, 35, 51, 58, 61, 68, 75-77, 89, 95, 140, 149,

157, 158

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We found a limited number of studies that reported on systems that linked patient-specific data with data from different specialty systems including laboratory results.29, 58, 61, 76, 77, 120, 151 These were used mainly to help detect high-risk patients and provide targeted support to individual prescribers.58, 61, 76, 77 Work on multi-faceted interventions that coordinated actions across multi-disciplinary teams, including active pharmacy interventions and medicines administration, was rare.29, 30, 68 A notable exception was work by Waitman and colleagues, who designed an electronic surveillance tool to identify high-risk medication orders and triggered pharmacy intervention to complement CPOE.68 Another study reported on a system that linked CPOE/CDS with pharmacy and medication administration.30

In terms of data re-use, we identified a number of studies that drew on ePrescribing system data to develop screening/surveillance tools for patients at risk for developing infections, 75, 157 to identify adverse drug events,89, 158 or to identify patients with antibiotic interventions.140 Others reported how data held within systems could help to predict appropriate therapies and dosages for high-risk patient groups,35, 58, 95, 149 and one study drew on machine learning approaches to improve the appropriate use of antibiotics in children with sepsis.51 Unfortunately, these studies did not describe how these data were used to trigger action across members of the multidisciplinary team other than prescribers (e.g. pharmacists).

DiscussionTo date, ePrescribing-based interventions to promote the appropriate use of antibiotics have been investigated mainly through small scale studies with designs prone to bias (mostly non-randomised retrospective observational single centre studies) (see Table 1). The majority of these were conducted in North American settings with “home-grown” and extensively customised systems. CPOE and CDSS were the most common system functionalities examined, but these varied widely across studies thereby complicating meaningful cross-study comparisons. Work surrounding more advanced functionalities that span wider organisational processes such as integration with laboratory results, pharmacy systems, and re-use of data was relatively scarce. Outcomes of existing work related mainly to individual performance of clinicians, followed by patient outcomes and cost assessments, with no attempts to investigate relationships and mechanisms across these dimensions. We also found a lack of insights into unintended sociotechnical consequences of interventions, which may help to in part explain the range of conclusions surrounding effectiveness across studies. A range of other factors such as different settings, populations, functionality, and outcomes assessed are also likely to play a role.

In undertaking this scoping review, we have provided an overall picture of the current evidence surrounding existing approaches to promoting the appropriate use of antibiotics through hospital ePrescribing systems and their outcomes (Figure 2). This illustrates the lack of attention paid to social contexts of use and the potential for developing broader organisational interventions associated with integration of ePrescribing systems with other functionalities and re-use of data. Our broad inclusion criteria meant that we included a wide range of studies with different designs, but we did not conduct formal quality assessments of included studies.164 This work now needs to be taken forward as a basis for designing and formally evaluating interventions employing rigorous methods to evaluate the impact of hospital ePrescribing systems to promote the appropriate use of antibiotics on patient outcomes. Central components of such interventions need to build on the existing literature, as identified in our work, and on existing guidance surrounding the development

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and evaluation of complex interventions.165 Ideally, future work should consist of multi-centre cluster randomised controlled trials with embedded qualitative and economic evaluation. Given the complex effects of ePrescribing systems and variety of settings in which they are implemented, randomised controlled trials may not be feasible, in which case quasi-experimental studies may be considered. In this context paying attention to both social and technical dimensions of change, 166 as well as drawing on longitudinal quantitative and qualitative designs is central for going forward as this will allow a degree of comparison across settings and systems.167 Sociotechnically informed work can also help to ensure that improvements in practitioner performance effectively translate to improvements in patient outcomes and cost-effectiveness. Here, examination of technical features and in particular user interfaces, as well as exploring social and organisational factors such as user training will be important. In due course, evidence obtained from evaluations of interventions with rigorous designs can then be aggregated through more formal systematic reviews.168, 169

The likely difficulty for any future work in this area is the complexity of interventions. These are likely to consist of multiple components accompanied with organisational change initiatives in specific settings. As a result, evaluators will be faced with challenges surrounding which observed effects are due to which interventional aspects.165, 170 Embedded qualitative work can help to mitigate this risk and facilitate insights into which components are potentially transferable between settings and systems. Such work is also urgently needed to gain deeper insights into “alert fatigue” and impact on time amongst users as well as other reasons as to why systems may not be effectively used.171, 172

In parallel to such efforts, it is imperative to more thoroughly explore interventions that draw on electronic data held within systems for re-use to improve the appropriate use of antibiotics and other more innovative approaches as these are likely to present the biggest returns on investment.173 Such work is currently extremely scarce in the empirical literature surrounding the appropriate use of antibiotics, which focuses mainly on approaches to improve practitioner performance, as opposed to interventions that inform more general organisational functioning through iterative cycles of feedback. Such work may involve identifying local and health system patterns of antibiotic resistance or feeding back performance data relating to antimicrobial prescribing to individual clinicians and/or units. This will help to ensure to build learning health systems thereby helping to improve safety, quality and efficiency of care more generally.174

ConclusionsWe have provided a starting point for developing interventions in an area of increasing interest internationally, by scoping the literature to identify existing and emerging approaches to ePrescribing-based interventions to promote the appropriate use of antibiotics. Next there is the need for a more focused systematic review on effectiveness and cost-effectiveness of ePrescribing functionalities, which we now plan to carry out.

Systems clearly have much potential in improving practitioner performance and patient outcomes, and reducing cost. However, more rigorous multi-faceted interventions now need to be developed and carefully evaluated to take this work forward and help to extract potentially transferable lessons across settings and systems. In relation to systems design, there are various options that can help to promote the appropriate use of antibiotics. These include changing existing systems (this requires suppliers to be engaged in changing their systems), customising systems (local change based on guidelines), or building new standard systems as an add-on to existing ePrescribing functionality.

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Whatever the approach, appropriate organisational and social components will need to play an essential part in approaches going forward and there is a clear need to pay closer attention to developing interventions with a broader organisational focus.

Competing interests: All authors declare that they have no competing interests.

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Tables and FiguresFigure 1: PRISMA diagram of included studies

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Box 1: Summary of outcomes measured across studies

Practitioner performance

Choice of antibiotic

Turnaround time for first dose of antibiotic

Antibiotic dosing

Adherence to protocols/guidelines

Total antibiotic use

Patient outcomes

Adverse drug events

Mortality

Length of hospital stay associated with antibiotics

Cost effectiveness

Total antibiotic expenditure

Future resistance

Cost of hospitalisation

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811

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813

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Figure 2: Emerging dimensions surrounding ePrescribing-based approaches to promote the appropriate use of antibiotics identified in the scoping review and areas for future work

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