The relevance of therapeutic positioning in the post-approval evaluation of new medicines. / La importancia del posicionamiento terapéutico en la evaluación posautorización de nuevos medicamentos.

The objective of regulatory authorities is to ensure a favorable risk-benefit balance for medicines in their licensed indication, without seeking to establish their place in the therapeutic armamentarium beyond that. The licensed indication covers heterogeneous subpopulations and often does not sufficiently specify the characteristics of the patients who may benefit. The regulatory information does not always show the benefit over the standard treatments; moreover, it only reacts to the conditions specified in the developer's application, and lacks an assessment of the clinical relevance of the benefit and its uncertainties. Many cases highlight the need to establish a more specific therapeutic benefit scenario than the licensed indication. For example, abemaciclib was approved in the adjuvant setting for high-risk patients with early breast cancer, but the appropriate level of risk and how to assess it needs to be specified. Also, pembrolizumab is approved for neoadjuvant plus adjuvant treatment in lung cancer; but it remains to be analyzed whether it is superior to nivolumab in neoadjuvant treatment alone, which involves less treatment and economic burden. As therapeutic positioning is always a necessary decision, whether made at a national, regional, local or individual level, it must be made in the most appropriate way. The absence of a multidisciplinary discussion and consensus, relying only on individual decisions to determine positioning from the outset, underestimates information gaps, inter-individual variability and the influence of drug promotion. It can be harmful and costly. To properly manage the introduction of new medicines, it is essential to establish their benefit scenario in a multidisciplinary way. This, together with consideration of the clinical benefit provided versus the appropriate alternatives and the uncertainties of the benefit, constitutes the objective of the clinical assessment and the basis for designing a well-focused economic analysis. This allows policy makers to make the most appropriate decisions on pricing and funding new treatments. In an ideal situation, the benefit scenario considered for the new medicine would coincide with the one established for funding, but costs that are difficult to bear may lead to restrictions and affect the final positioning after the economic and budgetary impact assessment.

Modeling package size-conscious automated dispensing cabinet replenishment to improve efficiency.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Optimization of automated dispensing cabinets (ADCs) has traditionally focused on modifying the inventory within these devices and ignored the replenishment process itself. Rounding replenishment quantities to the nearest package size, termed package size-conscious replenishment (PSCR), was investigated as a way to optimize labor needs for ADC replenishment. METHODS: A simulation of PSCR for a subset of medications stocked in ADCs at the University of North Carolina Medical Center was conducted. The simulation utilized real-world vend data and rounding factors to model the impact of PSCR on key ADC metrics. The final simulation utilized 2 months of ADC transactions across 410 medications in 149 ADCs. Four replenishment methodologies were simulated: standard replenishment and 3 PSCR strategies, including rounding down, rounding any direction, and rounding up. RESULTS: All 3 PSCR methodologies had significantly lower stockout frequencies than standard replenishment at 0.722% (P = 0.026) for rounding down, 0.698% (P = 0.024) for rounding any direction, and 0.680% (P = 0.024) for rounding up vs 0.773% for standard replenishment. PSCR methods were associated with significant time savings for both technician and pharmacist activities (P < 0.001 for all 3 strategies), with a savings of up to 0.27 technician and 0.52 pharmacist full-time equivalents estimated for the rounding-up methodology. Maximum carrying cost was higher for all 3 PSCR methodologies. CONCLUSION: PSCR was modeled to significantly decrease both pharmacist and technician time needed to replenish ADCs while also decreasing stockout frequency. Modest increases in maximum carrying cost were also shown. The simulation created for this evaluation could also be utilized to model other components of the ADC replenishment process.

Exploring susceptibility factors to medication dispensing errors through a retrospective study of patient-reported dispensing errors over 11 years: are dispensing errors indeed due to personal reasons for pharmacists?

BACKGROUND: Medication dispensing errors cause wastage of medicines and increase healthcare costs, with serious consequences for patients. However, few studies have systematically and completely reviewed dispensing errors, with inadequate attention to the objective regularity and risk factors for dispensing errors. OBJECTIVES: To explore the potential causes and risk factors influencing the prevalence of medication dispensing errors. METHODS: We collected patient-reported medication dispensing errors from a large tertiary care hospital in South China over 11 years. We assessed the characteristics of dispensing errors, labelled the causes, compared them with more than 25 million prescriptions from 2012 to 2022, identified the susceptibility factors for the occurrence of dispensing errors, and analysed the characteristics and patterns of the errors. RESULTS: A total of 376 patient-reported dispensing errors were recorded. It took an average of 5.2 days for a patient to find an error. Only 37.5% of errors were reviewed by the patient within 24 hours. These errors directly contributed to a medication loss of US$188 406. Of the 160 recorded pharmacists, 112 (70%) committed dispensing errors. Dispensing errors were affected by the pharmacists' use of the machine, workload and the length of monthly vacation. Of the dispensing errors, 47.9% (n=180) were caused by medication packaging or names that were similar. Antibiotics (n=32, 8.5%) were the most common types of drugs dispensed incorrectly, and traditional Chinese medicines (n=31, 8.2%) and immunosuppressants (n=21, 5.6%) were the most likely to be dispensed in inaccurate quantities. CONCLUSIONS: Organising adequate staff and using machines to prepare medicines may be necessary to reduce dispensing errors. When pharmacists have been away from work for more than 72 hours they should find their rhythm in other positions before dispensing medicines. It is more important to prioritise the differentiation of medicines with similar packaging over those with similar names when arranging drug shelving.

Natural language processing assisted detection of inappropriate proton pump inhibitor use in adult hospitalised patients.

OBJECTIVES: To establish a clinical application monitoring system for proton pump inhibitors (PPI-MS) and to enhance the detection and intervention of inappropriate PPI use in adult hospitalised patients. METHODS: Natural language processing technology was applied to indication recognition of therapeutic PPI applications and the assessment of admission record recognition for preventive PPI applications. Symptom judgement was based on the tense-negation model and regular expressions. Evidence-based rules for clinical PPI application were embedded for the construction of PPI-MS. A total of 9421 patient records using PPI from July 2022 to July 2023 were analysed to validate the performance of the system and to identify common issues related to inappropriate clinical PPI use. RESULTS: Out of 9421 hospitalised patients detected using PPI, 4736 (50.27%) were used for prophylaxis and the rest for therapeutic use. Among the prophylactic medications, 2274 patients (48.02%) were identified as receiving inappropriate prophylactic PPI. The main reasons were inappropriate prophylaxis without indication. Additionally, 258 cases of inappropriate therapeutic PPI use were identified, mainly involving the use of esomeprazole for peptic ulcers and Zollinger-Ellison syndrome. The efficiency of the PPI rational medication monitoring system, when coupled with human involvement, was 32 times that of manual monitoring. Among cases of inappropriate prophylactic PPI use, 45.29% were due to lack of indications, 28.34% involved inappropriate administration routes, 15.74% were related to inappropriate dosing frequencies and 10.62% were attributed to inappropriate drug selection. There were 933 cases related to the use of antiplatelet and anticoagulant drugs and 708 cases related to the use of non-steroidal anti-inflammatory drugs. The overall accuracy of the PPI-MS system was 88.69%, with a recall rate of 99.33%, and the F1 score was 93.71%. CONCLUSIONS: Establishing a PPI medication monitoring system through natural language processing technology, while ensuring accuracy and recall rates, improves evaluation efficiency and homogeneity. This provides a new solution for timely detection of issues relating to clinical PPI usage.

Evaluation of Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitor Prescribing Patterns in Heart Failure Patients at Hospital Discharge.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) dapagliflozin and empagliflozin are indicated for heart failure with reduced ejection fraction (HFrEF) for cardiovascular death and heart failure hospitalization risk reduction. Due to the recent nature of these data, prescribing of SGLT2is may be suboptimal. Objective: This study sought to assess the prevalence of SGLT2i prescriptions at hospital discharge for HFrEF. Methods: A retrospective chart review was conducted on HFrEF patients discharged from April 1st to December 31st, 2021 from one academic medical center in the United States. The primary objective was to determine the percentage of eligible patients prescribed SGLT2i at discharge and the secondary objective was to characterize covariates impacting prescription. Results: Overall, 115 patients were included. The mean age was 72 ± 14.25 years. The majority were male (73.9%) and Caucasian (74.8%). At discharge, 15.7% of patients were prescribed an SGLT2i, although 94.8% were eligible. Baseline characteristics and concomitant medications did not differ significantly, although the mean number of discharge medications differed significantly between those prescribed an SGLT2i (15.78 ± 6.77) and those not (12.05 ± 5.28) (P = 0.023). Conclusions: SGLT2is are under-prescribed at discharge for HFrEF patients, despite many being eligible. Further studies should be done to elucidate factors that influence the under-prescription of SGLT2is.

Enhancing Hospital Pharmacy Operations Through Lean and Six Sigma Strategies: A Systematic Review.

Hospital pharmacies are integral to the healthcare system, and evaluating the factors influencing their efficiency and service standards is imperative. This analysis offers global insights to assist in developing strategies for future enhancements. The objective is to identify the optimal Lean Six Sigma methodologies to improve workflow and quality of hospital pharmacy services. A strategic search, aligned with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, encompassed an extensive range of academic databases, including Scopus, PubMed/Medline, Web of Science, and other sources for relevant studies published from 2009 to 2023. The focus was on management tactics and those examining outcomes, prioritizing publications reflecting pharmacy operations management's state. The quality of the selected articles was assessed, and the results were combined and analyzed. The search yielded 1,447 studies, of which 73 met the inclusion criteria. The systematic review found a low to moderate overall risk of bias. The number of publications rose during the coronavirus disease (COVID-19) outbreak. Among studies, research output in the United States of America represented 26% of the total. Other countries such as Indonesia, Spain, Canada, China, Saudi Arabia, the United Arab Emirates, and the United Kingdom also made significant contributions. Each country accounted for 12%, 8%, 7%, 5%, 5%, 5%, and 5%, respectively. The pharmacy journals led with 26 publications, and healthcare/medical with 14. The quality category came next with 12 articles, while seven journals represented engineering. Studies used empirical and observational methods, focusing on practice quality enhancement. The process control plan had 26 instances, and the define, measure, analyze, improve, and control (DMAIC) was identified 13 times. The sort, set in order, shine, standardize, and sustain (5S) ranked third, totaling seven occurrences. Failure mode and effects analysis (FMEA) and root cause analysis were moderately utilized, with six and four instances, respectively. Poka-Yoke (mistake-proofing measures) and value stream mapping were each counted three times. Quality improvement and workflow optimization dominated managerial strategies in 22 (30.14%) studies each, followed by technology integration in 15 (20.55%). Cost, patient care, and staffing each featured in three (4.11%) studies, while two (2.74%) focused on inventory management. One (1.37%) study each highlighted continuing education, collaboration, and policy changes. Analysis of the 73 studies on Lean and Six Sigma in hospital pharmacy operations showed significant impacts, with 26% of studies reporting decreased medication turnaround time, 15% showing process efficiency improvements, and 11% each for enhanced inventory management and bottleneck/failure mode reduction. Additionally, 9% of studies observed decreased medication errors, 8% noted increased satisfaction and cost savings, 6% identified enhancements in clinical activities, 3% improved prescription accuracy, 2% reduced workflow interruptions, and 1% reported increased knowledge. Also, this study has identified key strategies for service delivery improvement and the importance of quality practices and lean leadership. To the best of the author's knowledge, this research is believed to be the first in-depth analysis of Lean and Six Sigma in the hospital pharmacy domain, spanning 15 years from 2009 to 2023.

Extravasation of brentuximab vedotin, an antibody-drug conjugate, in a patient with anaplastic large cell lymphoma.

Brentuximab vedotin (BV) is an antibody-drug conjugate, consisting of a CD30-directed antibody, conjugated by a protease-cleavable linker to a microtubule disrupting agent auristatin E (MMAE). Although the safety datasheet of BV does not warn of severe toxic effects of extravasation, we report a third case of a patient with anaplastic large cell lymphoma who developed severe epidermal necrosis after extravasation. The reason for what happened could be attributed to the fact that MMAE belongs to the group of vinca alkaloids so it should be handled like other tissue-necrotising chemotherapeutics. Reporting of all cases of extravasation involving new conjugated chemotherapeutic drugs is of the utmost importance to be able to develop updated guidelines. Hospital pharmacists can provide information on how to manage extravasation, assess the potential risk, and have a crucial role in drafting hospital protocols.

Increasing the Rate of Venous Thromboembolism Chemoprophylaxis Administration Using the Electronic Medical Record.

Introduction: Venous thromboembolism (VTE) remains a leading cause of preventable harm among hospitalized patients. Pharmacologic VTE prophylaxis reduces the rate of in-hospital VTE by 60%, but medication administration is often missed for various reasons. Electronic medical record (EMR) prompts may be a useful tool to decrease withholding of critical VTE chemoprophylaxis medications. Methods: In August 2021, an EMR prompt was implemented at a tertiary referral academic medical center mandating nursing staff to contact a provider for approval before withholding VTE chemoprophylaxis. A pre-intervention group from August 2020 to August 2021 was compared to a post-intervention group from August 2021 to August 2022. Rates of VTE chemoprophylaxis withholding were compared between the groups with a P < .01 considered significant. Results: A total of 16,395 patients prescribed VTE chemoprophylaxis were reviewed, with 13,395 (81.7%) receiving low molecular weight heparin. Of the 16,395 patients included, 10,701 (65.3%) were medical and 5694 (34.7%) were surgical. Patients in the pre-intervention cohort (n = 8803) and post-intervention cohort (n = 7592) were similar in hospital length of stay and duration of DVT prophylaxis. In the post-intervention group, the frequency of surgical patients with at least one missed dose had increased by 4.2% (P = .002), with the trauma and acute care surgery (TACS) show an increase of 6.6% (P < .001). However, the frequency of medical patients and non-TACS patients with missed doses decreased by 3.1% (P = .002) and 1.0% (<.001), respectively. Conclusions: EMR prompts appear to be a low-cost intervention that increases the rate of VTE prophylaxis administration among medical and elective surgery patients.

Understanding pathways to health-system pharmacy administration: A journey mapping study.

PURPOSE: Pharmacy administrators play a critical role in the success of health systems, yet pathways to pharmacy administration are incompletely understood. The purpose of this study was to explore and describe pathways to becoming a health-system pharmacy administrator, including challenges experienced and resources needed. METHODS: Participants (N = 21) individually completed one or more journey maps detailing the pathway(s) to pharmacy administration and then engaged in small group discussion to identify common themes. A large group debrief was used to share and identify findings across small groups. Thematic analysis was utilized to identify common ideas shared. RESULTS: There was variation across the maps, illustrating many steps one might follow to become a pharmacy administrator. In the 23 maps completed, pathways most frequently began with pharmacy school (n = 9, 39.1%), high school (n = 6, 26.1%), or undergraduate training (n = 4, 17.4%). Most included residency training or dual master's of science in health-system pharmacy administration/residency training (n = 16, 69.6%). Common challenges included distractions, time constraints, grades/performance, financial constraints, and stress. Common resources needed included exposure to diverse career paths, pipeline and outreach support, mentoring, and leadership. Themes included debate about the definition of a pharmacy administrator, questions regarding the core competencies of the pharmacy administrator, discussion regarding ways to enter pharmacy administration, and reflection on the role of serendipity and networking. CONCLUSION: Understanding the pathways to pharmacy administration is critical to fostering a sustainable and competent workforce. Work must be done to identify strategies and develop processes for identifying, equipping, and retaining talented health-system pharmacy administrators and leaders.

Investigation and analysis of pharmaceutical management in compact medical consortium of Guangdong province / 中国药房

OBJECTIVE To investigate the current situation of pharmaceutical management in compact medical consortium of Guangdong province， and to provide decision-making basis for promoting the high-quality construction and sustainable development of the provincial medical consortium. METHODS A self-designed questionnaire was used to select 50 compact medical consortiums in Guangdong province. The survey was answered by the heads of the pharmacy department of the general hospitals. The survey covered the basic scale of the consortium， the appointment of chief pharmacists， the implementation of pharmaceutical management and pharmaceutical care homogenization within the consortium， the difficulties in promoting the homogenization， and the expected provincial support. Descriptive statistical analysis was performed on the survey results. RESULTS A total of 50 questionnaires were collected， and the effective recovery rate was 100%. There were 16 chief pharmacists （32.00%） in charge of the pharmacy department of the general hospital in the medical consortium. Thirty-seven medical consortiums （74.00%） had established a drug supply support system within the consortium， 35 medical consortiums （70.00%） had carried out pharmaceutical management and coordination work within the medical consortium， 23 medical consortiums （46.00%） had established a clinical medication guidance system， 25 medical consortiums chenwenying2016@163.com （50.00%） had established a bidirectional communication mechanism， and only 8 medical consortiums （16.00%） had developed new models of pharmaceutical care. At present， the difficulties in promoting the homogenization of pharmaceutical management and pharmaceutical care within the medical consortium were mainly found in three aspects： the wide gap in management level of each member unit， the lack and uneven level of pharmaceutical personnel， and insufficient policy support and implementation. Most medical consortiums hoped that relevant departments could promote the homogenization of pharmaceutical work by holding special training courses or special supervision. CONCLUSIONS At present， the compact medical consortium in Guangdong province has achieved initial results in the implementation of the chief pharmacist system， the homogenization of pharmaceutical management and pharmaceutical care. However， it is still necessary to improve the coverage of chief pharmacist appointments in the medical consortium， implement the homogenization of pharmaceutical management， and accelerate the homogenization process of pharmaceutical care.

The Role of a Pharmacy Administration and Leadership Rotation within Postgraduate Year Two Critical Care Residency Training.

Introduction: The job of a critical care pharmacy specialist has evolved to include quality improvement and administrative tasks. As such, the American Society of Health-System Pharmacists (ASHP) highlights specific goals and objectives to ensure post-graduate year two (PGY2) critical care residents are sufficiently trained to perform these tasks. The PGY2 critical care pharmacy residency leadership at the University of Kentucky sought to develop a four-week learning experience entitled, "Critical Care Administration / Medication Use Quality & Outcomes," as a unique rotation to capture these requirements and activities. Objectives: The focus of this commentary is to serve as a guide for other residency programs to develop such a rotation, highlight resulting resident contributions to the department, describe perceived benefits of this rotation for residents, and highlight how this rotation impacted graduated residents' early years as practitioners. Conclusions: This learning experience is pivotal to providing a more balanced view of the entire medication use process and the healthcare ecosystem during a specialty residency. PGY2 critical care residents can gain valuable experiences away from the bedside that better prepare them for future tasks in addition to patient care that will be expected of them as clinical pharmacists.

Systematic review of room temperature stability of key beta-lactam antibiotics for extended infusions in inpatient settings.

BACKGROUND: Extended infusion (EI) of beta-lactam antibiotics may offer clinical benefits aligned with improved probability of target attainment for critical pharmacokinetic/pharmacodynamic parameters that correlate with efficacy. There is much research interest in prolonged and continuous infusions (collectively, extended infusions) of beta-lactams to improve patient outcomes, particularly in critically ill patients in intensive care. While definitive clinical trial data demonstrating beneficial outcomes is awaited, there has been limited focus on the stability of the agents given by EI, which may be an equally critical parameter. EI may allow for savings in nursing time due to reduced need for drug reconstitution. We set out to examine the data for stability for EI at room temperature, consistent with the requirements of 'A Standard Protocol for Deriving and Assessment of Stability- Part 1 Aseptic Preparation (Small Molecules)', which allows a 5% loss of active pharmaceutical ingredient (API) applicable for those territories that use the British Pharmacopoeia also for a 10% loss applicable in much of rest of the world. METHODS: Searches using preferred reporting items for systematic reviews and meta-analyses (PRISMA) principles for stability data on freshly prepared beta-lactam antimicrobials for extended administration at room temperature (at or above 23°C) were conducted in November 2021 and updated in December 2022. RESULTS: We found data to support the extension of the shelf life of 12 key beta-lactam antibiotics once reconstituted (aztreonam, amoxicillin, benzylpenicillin, flucloxacillin, piperacillin/tazobactam, cefazolin, cefmetazole, ceftaroline, ceftazidime, ceftriaxone, imipenem and meropenem) compliant with the NHS protocol, and data for five other agents (ticarcillin, cefepime, cefiderocol, cefoxitin and doripenem) which would be acceptable in regions outside the UK beyond that listed in the Summary of Product Characteristics.This review has not been registered under PROSPERO.

Regulating Pharmacist Clinical Services: Is Legal Silence Golden or Deafening?

In the United States, the scope of practice of pharmacists is determined primarily at the state level. Not all state laws expressly permit or prohibit pharmacists from providing certain services; in between is a grey area of legal silence. Does legal silence permit pharmacists to perform a service that is not specifically permitted, but not expressly prohibited? Point-of-care testing provides a useful case study in legal silence: there are 1536 pharmacies currently holding a CLIA-waiver to administer tests in states reporting that pharmacists are not expressly permitted to administer tests. Legal silence may even provide a better framework for pharmacy based testing as it is naturally inclusive of any point-of-care test and no laws need updated when a new test comes to the market. Other health professions navigate this legal silence by governing according to a "standard of care." Rather than specifying a list of services a health professional can or cannot provide in law, it provides a flexible framework for the health professional to provide any service that other similarly situated health professionals would provide in the same or similar situation. A standard of care regulatory framework should thus be the target of the pharmacy profession in order to advance patient care.

Physicians' and nurses' perceptions of the factors influencing the implementation of paediatric clinical pharmacy services in Hong Kong: a qualitative study.

OBJECTIVES: To identify barriers and facilitators that influence the implementation of paediatric clinical pharmacy services in Hong Kong public hospitals from physicians' and nurses' perspectives. METHODS: A qualitative study was conducted based on semistructured interviews of physicians and nurses who worked in the field of paediatrics in four public hospitals in Hong Kong. Interviews were held via telephone conversations using spoken Cantonese which were audio recorded, then translated and transcribed directly into English by the research team. Thematic analysis was used for data analysis and reflexivity was engaged through member checking, making field notes and reporting using the Consolidated Criteria for Reporting Qualitative Studies checklist. RESULTS: A total of six barriers and five facilitators were identified from interviewing 17 participants, which included 7 physicians and 10 nurses. The barriers identified were the public's lack of understanding and recognition of clinical pharmacists, a culture of medical dominance, lack of resources and heavy workload, the need for a more transparent and defined role of clinical pharmacist at the institutional level, lack of proactive approach and involvement in direct patient care activities. The facilitators identified were the belief in the improvement of patient outcomes and the overall pharmaceutical service efficiency, trust and confidence in clinical pharmacy services, filling the clinical gap as a medicine information provider, and direct and coherent communication as a multidisciplinary team member. CONCLUSIONS: Physicians and nurses reported that the implementation of paediatric clinical pharmacy services was adequate, but several key barriers were identified at both the external and internal levels.

Automation of the medication process in Swiss hospitals: results of a survey.

OBJECTIVES: Medication management is a core process in hospital administration. The safety, timeliness and efficiency of medication distribution may be improved by automating logistical and administrative aspects of the process. Forming an accurate high-level picture of current practices may help decision-makers to better advance the state of automation. This study aims to identify which systems for automating the medication process are currently in use in Swiss hospitals, and to what extent each system is used. METHODS: A 27-question survey was developed and distributed to Swiss Association of Public Health Administration and Hospital Pharmacists (GSASA) members. The survey focused on enterprise resource planning (ERP) systems, automation of in-hospital distribution and dispensing of pharmaceutical goods, bedside scanning, and the management of drug master data. RESULTS: The response rate was 98% (58/59 hospital pharmacies). All institutions had an ERP system in use, most frequently SAP (n=23, 39%). Electronic invoices from suppliers were fully processed by 37% and partially processed by 17% of respondents. Twenty-five percent of respondents reported performing bedside scanning for the purpose of medication administration. Automated medication distribution systems were available in 20 hospitals (34%), of which 13 were central robots and seven were decentralised systems. CONCLUSION: A considerable gap remains to achieve closed loop processes between multiple systems. The present results provide an inventory of existing systems and current trends for use by decision-makers in hospitals and hospital pharmacies.