A cost comparison of pembrolizumab: Fixed and weight-based dosing.

BACKGROUND: Pembrolizumab, an immune checkpoint inhibitor, indicated to treat multiple cancers, was initially approved in Australia as weight-based dosing at 2 mg/kg every 3 weeks (Q3W). Subsequent approvals used 'fixed' dosages of 200 mg Q3W or 400 mg every 6 weeks (Q6W). Pharmacokinetic equivalence was demonstrated between dosing strategies, with no significant differences in efficacy or toxicity. Fixed dosing regimens are routinely used in Australia. AIM: To model and compare the cost of weight-based dosing of pembrolizumab to standard fixed dosing regimens. METHOD: A single centre, retrospective review was conducted. Patients, identified from dispensing software, who commenced on pembrolizumab between January and December 2022 were included. Patient demographic and treatment data was extracted from electronic medical records. Costs of weight-based doses were calculated and compared to the cost of fixed dosing. Variables such as acquisition cost, funding mechanisms and 'vial sharing' were considered. RESULTS: Fifty-two patients were included (63% male, median age 68 years). Of the 211 doses of pembrolizumab administered (average 4.1 doses/patient), 161 were Q3W doses, and 50 were Q6W doses. The acquisition cost for a fixed 200 mg and 400 mg dose was $7646, and $15,292, respectively. The average patient weight was 77.6 kg (SD 19 kg), which equated to $5933 for a weight-based Q3W dose, and $11,867 for the Q6W dose; a potential cost avoidance of $1965 and $3930 per dose, respectively. This represented a possible 23.5% avoidance in medication acquisition cost. Over the study period of 1 year, using weight-based dosing for pembrolizumab had the potential to reduce medication expenditure by $467,996. DISCUSSION: Significant cost avoidance could be achieved via weight-based pembrolizumab dosing. Given the substantial total cost of pembrolizumab, the growing number of indications and the expected equivalent treatment outcomes with weight-based pembrolizumab, the potential cost reductions of weight-based pembrolizumab at both institution and government level should be further explored.

An e-Delphi study to obtain expert consensus on the level of risk associated with preventable e-prescribing events.

AIMS: We aim to seek expert opinion and gain consensus on the risks associated with a range of prescribing scenarios, preventable using e-prescribing systems, to inform the development of a simulation tool to evaluate the risk and safety of e-prescribing systems (ePRaSE). METHODS: We conducted a two-round e-Delphi survey where expert participants were asked to score pre-designed prescribing scenarios using a five-point Likert scale to ascertain the likelihood of occurrence of the prescribing event, likelihood of occurrence of harm and the severity of the harm. RESULTS: Twenty-four experts consented to participate with 15 pand 13 participants completing rounds 1 and 2, respectively. Experts agreed on the level of risk associated with 136 out of 178 clinical scenarios with 131 scenarios categorised as high or extreme risk. CONCLUSION: We identified 131 extreme or high-risk prescribing scenarios that may be prevented using e-prescribing clinical decision support. The prescribing scenarios represent a variety of categories, with drug-disease contraindications being the most frequent, representing 37 (27%) scenarios, and antimicrobial agents being the most common drug class, representing 28 (21%) of the scenarios. Our e-Delphi study has achieved expert consensus on the risk associated with a range of clinical scenarios with most of the scenarios categorised as extreme or high risk. These prescribing scenarios represent the breadth of preventable prescribing error categories involving both basic and advanced clinical decision support. We will use the findings of this study to inform the development of the e-prescribing risk and safety evaluation tool.

Variation in approaches to antimicrobial use surveillance in high-income secondary care settings: a systematic review.

INTRODUCTION: In secondary care, antimicrobial use (AMU) must be monitored to reduce the risk of antimicrobial resistance and infection-related complications. However, there is variation in how hospitals address this challenge, partly driven by each site's level of digital maturity, expertise and resources available. This systematic review investigated approaches to measuring AMU to explore how these structural differences may present barriers to engagement with AMU surveillance. METHODS: We searched four digital databases and the websites of relevant organizations for studies in high-income, inpatient hospital settings that estimated AMU in adults. Excluded studies focused exclusively on antiviral or antifungal therapies. Data were extracted data on 12 fields (study description, data sources, data extraction methods and professionals involved in surveillance). Proportions were estimated with 95% CIs. RESULTS: We identified 145 reports of antimicrobial surveillance from Europe (63), North America (53), Oceania (14), Asia (13) and across more than continent (2) between 1977 and 2018. Of 145 studies, 47 carried out surveillance based on digital data sources. In regions with access to electronic patient records, 26/47 studies employed manual methods to extract the data. The majority of identified professionals involved in these studies were clinically trained (87/93). CONCLUSIONS: Even in regions with access to electronic datasets, hospitals rely on manual data extraction for this work. Data extraction is undertaken by healthcare professionals, who may have conflicting priorities. Reducing barriers to engagement in AMU surveillance requires investment in methods, resources and training so that hospitals can extract and analyse data already contained within electronic patient records.

Complex Hospital-Based Electronic Prescribing-Based Intervention to Support Antimicrobial Stewardship: Qualitative Study.

BACKGROUND: Antimicrobial resistance (AMR) represents a growing concern for public health. OBJECTIVE: We sought to explore the challenges associated with development and implementation of a complex intervention designed to improve AMS in hospitals. METHODS: We conducted a qualitative evaluation of a complex AMS intervention with educational, behavioral, and technological components in 5 wards of an English hospital. At 2 weeks and 7 weeks after initiating the intervention, we interviewed 25 users of the intervention, including senior and junior prescribers, a senior nurse, a pharmacist, and a microbiologist. Topics discussed included perceived impacts of different elements of the intervention and facilitators and barriers to effective use. Interviews were supplemented by 2 observations of ward rounds to gain insights into AMS practices. Data were audio-recorded, transcribed, and inductively and deductively analyzed thematically using NVivo12. RESULTS: Tracing the adoption and impact of the various components of the intervention was difficult, as it had been introduced into a setting with competing pressures. These particularly affected behavioral and educational components (eg, training, awareness-building activities), which were often delivered ad hoc. We found that the participatory intervention design had addressed typical use cases but had not catered for edge cases that only became visible when the intervention was delivered in real-world settings (eg, variations in prescribing workflows across different specialties and conditions). CONCLUSIONS: Effective user-focused design of complex interventions to promote AMS can support acceptance and use. However, not all requirements and potential barriers to use can be fully anticipated or tested in advance of full implementation in real-world settings.

Developing consensus on hospital prescribing indicators of potential harms amenable to decision support.

AIMS: To develop a list of prescribing indicators specific for the hospital setting that would facilitate the prospective collection of high-severity and/or high-frequency prescribing errors, which are also amenable to electronic clinical decision support. METHODS: A two-stage consensus technique (electronic Delphi) was carried out with 20 experts across England. Participants were asked to score prescribing errors using a five-point Likert scale for their likelihood of occurrence and the severity of the most likely outcome. These were combined to produce risk scores, from which median scores were calculated for each indicator across the participants in the study. The degree of consensus between the participants was defined as the proportion that gave a risk score in the same category as the median. Indicators were included if a consensus of 80% or more was achieved. RESULTS: A total of 80 prescribing errors were identified by consensus as being high or extreme risk. The most common drug classes named within the indicators were antibiotics (n = 13), antidepressants (n = 8), nonsteroidal anti-inflammatory drugs (n = 6) and opioid analgesics (n = 6). The most frequent error type identified as high or extreme risk were those classified as clinical contraindications (n = 29 of 80). CONCLUSIONS: Eighty high-risk prescribing errors in the hospital setting have been identified by an expert panel. These indicators can serve as a standardized, validated tool for the collection of prescribing data in both paper-based and electronic prescribing processes. This can assess the impact of safety improvement initiatives, such as the implementation of electronic clinical decision support.

On the alert: future priorities for alerts in clinical decision support for computerized physician order entry identified from a European workshop.

BACKGROUND: Clinical decision support (CDS) for electronic prescribing systems (computerized physician order entry) should help prescribers in the safe and rational use of medicines. However, the best ways to alert users to unsafe or irrational prescribing are uncertain. Specifically, CDS systems may generate too many alerts, producing unwelcome distractions for prescribers, or too few alerts running the risk of overlooking possible harms. Obtaining the right balance of alerting to adequately improve patient safety should be a priority. METHODS: A workshop funded through the European Regional Development Fund was convened by the University Hospitals Birmingham NHS Foundation Trust to assess current knowledge on alerts in CDS and to reach a consensus on a future research agenda on this topic. Leading European researchers in CDS and alerts in electronic prescribing systems were invited to the workshop. RESULTS: We identified important knowledge gaps and suggest research priorities including (1) the need to determine the optimal sensitivity and specificity of alerts; (2) whether adaptation to the environment or characteristics of the user may improve alerts; and (3) whether modifying the timing and number of alerts will lead to improvements. We have also discussed the challenges and benefits of using naturalistic or experimental studies in the evaluation of alerts and suggested appropriate outcome measures. CONCLUSIONS: We have identified critical problems in CDS, which should help to guide priorities in research to evaluate alerts. It is hoped that this will spark the next generation of novel research from which practical steps can be taken to implement changes to CDS systems that will ultimately reduce alert fatigue and improve the design of future systems.

A complex ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention for hospitals combining technological and behavioural components: protocol for a feasibility trial.

BACKGROUND: Antimicrobial resistance is a leading global public health threat, with inappropriate use of antimicrobials in healthcare contributing to its development. Given this urgent need, we developed a complex ePrescribing-based Anti-Microbial Stewardship intervention (ePAMS+). METHODS: ePAMS+ includes educational and organisational behavioural elements, plus guideline-based clinical decision support to aid optimal antimicrobial use in hospital inpatients. ePAMS+ particularly focuses on prompt initiation of antimicrobials, followed by early review once test results are available to facilitate informed decision-making on stopping or switching where appropriate. A mixed-methods feasibility trial of ePAMS+ will take place in two NHS acute hospital care organisations. Qualitative staff interviews and observation of practice will respectively gather staff views on the technical component of ePAMS+ and information on their use of ePAMS+ in routine work. Focus groups will elicit staff and patient views on ePAMS+; one-to-one interviews will discuss antimicrobial stewardship with staff and will record patient experiences of receiving antibiotics and their thoughts on inappropriate prescribing. Qualitative data will be analysed thematically. Fidelity Index development will enable enactment of ePAMS+ to be measured objectively in a subsequent trial assessing the effectiveness of ePAMS+. Quantitative data collection will determine the feasibility of extracting data and deriving key summaries of antimicrobial prescribing; we will quantify variability in the primary outcome, number of antibiotic defined daily doses, to inform the future larger-scale trial design. DISCUSSION: This trial is essential to determine the feasibility of implementing the ePAMS+ intervention and measuring relevant outcomes, prior to evaluating its clinical and cost-effectiveness in a full scale hybrid cluster-randomised stepped-wedge clinical trial. Findings will be shared with study sites and with qualitative research participants and will be published in peer-reviewed journals and presented at academic conferences. TRIAL REGISTRATION: The qualitative and Fidelity Index research were approved by the Health and Research Authority and the North of Scotland Research Ethics Service (ref: 19/NS/0174). The feasibility trial and quantitative analysis (protocol v1.0, 15 December 2021) were approved by the London South East Research Ethics Committee (ref: 22/LO/0204) and registered with ISRCTN ( ISRCTN 13429325 ) on 24 March 2022.

The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.

How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.

Learning lessons from electronic prescribing implementations in secondary care.

This paper reports a study undertaken in the UK to gather lessons learned from hospital sites that have implemented electronic prescribing systems. The work was commissioned by NHS Connecting for Health, the UK Department of Health agency responsible for the implementation of the National Programme for Information Technology. The aim was to capture front-line experience of the project and systems implementation, and to share it with staff who will in the future participate in other implementations. Data were drawn from detailed interviews with staff and a survey in 13 hospitals in England, as well as a review of published studies of implementations. The study output is a report and six user-facing briefing documents targeted at key stakeholder groups; nurses, pharmacist, doctors, senior executives, implementation team members and IM&T staff.

A cross-country time and motion study to measure the impact of electronic medication management systems on the work of hospital pharmacists in Australia and England.

BACKGROUND: Qualitative studies have provided important insights into how hospital pharmacists' work changes when electronic medication management (EMM) systems are introduced. Quantitative studies of work practice change are rare. Despite the use of EMM systems internationally, there are no cross-country comparative studies of their impact on health professionals' work. We aimed to quantify and compare the type and magnitude of changes in hospital pharmacists' work pre- and post-EMM implementation in two countries. METHODS: Parallel, direct observational, time and motion studies of pharmacists in Australia and England pre- and post-EMM implementation. 20 pharmacists were observed: 9 in an Australian 440-bed hospital (155 h); and 11 pharmacists in a 500-bed English hospital (258 h). The Work Observation Method By Activity Timing (WOMBAT) software was used to collect observational data. Proportions of observed time in 11 tasks by study period (pre- versus post-EMM) and site, time spent with others or alone, and using different tools (e.g computers, paper) were calculated. Magnitude of changes between pre- and post-EMM by task and country were determined using z-tests for proportions adjusting for multiple testing. RESULTS: At baseline, Australian and English pharmacists spent the greatest proportion of time in medication review. Post-EMM, time in medication review (Australia 21.6%-27.5%; England 27.1%-33.8%) and history-taking (Australia 7.6%-13.3%; England 19.5%-28.9%) significantly increased. Despite country differences in these tasks at baseline, the magnitude of changes did not significantly differ. English pharmacists increased time engaged in medication discussions with patients post-EMM (from 5.9% to 10.8%; p = 0.01). The Australian rate did not change (18.0%-27.2%; p = 0.09), but was higher at baseline. Post-EMM, Australian pharmacists spent 63.4% of time working alone, compared to 92.0% for English pharmacists. CONCLUSIONS: EMM systems impacted the same core areas of work and had a similar magnitude of effect on pharmacists' work in both countries. Anticipated reductions in medication review and history taking were not observed.