Analysis of Spontaneously Reported Adverse Drug Events: Towards Developing Systems for Preventability.

Background: Analysing data on adverse drug reactions (ADRs) in health facilities is an essential step to help develop effective strategies to reduce their incidence. The objective was to analyse spontaneous ADR reports sent to the Ghanaian Food and Drugs Authority (FDA) by two reporting health facilities over 5 years. Methods: Data from duplicate spontaneous ADR reports sent to the FDA (Ghana) from 2014 to 2018 were extracted. The relationship between independent variables such as age, sex, and source of drugs and ADR outcomes was assessed with either chi-square or a Cramer's V test for association where appropriate. Results: Type A reactions (65.2%) were the most prevalent of the ADRs, followed by Type B (34.1%), with the majority (80%) of patients affected recovering fully. The majority of Type A reactions (54.1%) occurred in the clinic, while the majority of Type B reactions (43.5%) occurred in the hospital. The skin and central nervous system (CNS) were the most affected (70.8%) organs. A higher incidence of CNS and skin-related ADRs was recorded in patients older than 30 (RR = 1.28 (1.07-1.53)). Also, females were more likely to experience a CNS-related ADR. The seriousness of the ADR was found to be significantly associated with the (1) type of prescriber, (2) whether the drug was prescribed, or (3) whether the drug regimen prescribed was appropriate. Even though, in 86% of cases, the offending drug was withdrawn within the first 5 days, it exceeded 20 days in about 6% of cases. The record of allergy status in a patient's folder and the source of the drug were significantly associated with the chance that the offending drug was withdrawn. However, recording ADRs did not influence whether the offending drug was stopped. Conclusion: Most of the ADRs experienced by patients could be avoided if the current systems are improved to prevent the rechallenge of offending drugs. Efforts to improve and update patient medication records and steps to ensure continuity of care are essential in preventing these adverse drug events.

Effectiveness of a Mobile App (Meds@HOME) to Improve Medication Safety for Children With Medical Complexity: Protocol for a Randomized Controlled Trial.

BACKGROUND: This study will pilot-test the mobile app, Medication Safety @HOME-Meds@HOME intervention to improve medication administration accuracy, reduce preventable adverse drug events, and ultimately improve chronic care management for children with medical complexity (CMC). The Meds@HOME app was co-designed with CMC families, secondary caregivers (SCGs), and health professionals to support medication management for primary caregivers (PCGs) and SCGs of CMC. We hypothesize that Meds@HOME will improve caregivers' medication administration accuracy, reduce preventable adverse drug events, and ultimately improve chronic care management. OBJECTIVE: This study aims to evaluate the effectiveness of Meds@HOME on medication administration accuracy for PCGs and SCGs. METHODS: This study will recruit up to 152 PCGs and 304 SCGs of CMC who are prescribed at least 1 scheduled high-risk medication and receive care at the University of Wisconsin American Family Children's Hospital. PCGs will be randomly assigned, for the 6-month trial, to either the control group (not trialing Meds@HOME) or the intervention group (trialing Meds@HOME) using 1:1 ratio. The Meds@HOME app allows caregivers to create a child profile, store medication and care instructions, and receive reminders for upcoming and overdue care routines and medication refills. Surveys completed both at the start and end of the trial measure demographics, medication delivery knowledge, confidence in the CMC's caregiving network, and comfort with medical information. Univariate and multivariate generalized estimation equations will be used for primary statistical analysis. The primary outcome is the PCG's rate of medication administration accuracy measured as correct identification of each of the following for a randomly selected high-risk medication: indication, formulation, dose, frequency, and route at baseline and after 6 months. Secondary outcomes include SCG medication administration accuracy (indication, formulation, dose, frequency, and route), count of University of Wisconsin hospital and emergency department encounters, PCG-reported medication adherence, count of deaths, and PCG medication confidence and understanding. RESULTS: Recruitment for this study began on November 29, 2023. As of May 15, 2024, we have enrolled 94/152 (62%) PCGs. We expect recruitment to end by August 1, 2024, and the final participant will complete the study by January 28, 2025, at which point we will start analyzing the complete responses. We expect publication of results at the end of 2025. CONCLUSIONS: The Meds@HOME mobile app provides a promising strategy for improving PCG medication safety for CMC who take high-risk medications. In addition, this protocol highlights novel procedures for recruiting SCGs of CMC. In the future, this app could be used more broadly across diverse caregiving networks to navigate complex medication routines and promote medication safety. TRIAL REGISTRATION: ClinicalTrials.gov NCT05816590; https://clinicaltrials.gov/study/NCT05816590. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/60621.

Prevalence of actionable pharmacogenetic variants and high-risk drug prescriptions: A Swiss hospital-based cohort study.

Drug type and dosing recommendation have been designed and optimized based on average response in the general population. Yet, there is significant inter-individual variability in drug response, which results in treatment inefficacy or adverse drug reactions in a subset of patients. This is partly due to genetic factors that typically affect drug metabolism or clearance. To verify the relevance and applicability of international pharmacogenetic guidelines in the Swiss population, we genotyped 1533 patients from a hospital-based biobank who received at least 30 different drugs, as documented in their electronic health record. We then assessed the prevalence of clinically actionable variants in 13 high-risk pharmacogenes. We compared the allele frequencies obtained in the hospital-based cohort with those of a Swiss population-based cohort of 4791 individuals. The prevalence of clinically actionable variants was comparable between the two cohorts, with most study participants (97.3%) carrying at least one actionable pharmacogenetic variant. We then assessed the frequency of high-risk prescriptions due to actionable gene-drug interactions and observed that 31% of patients in the hospital-based cohort were prescribed at least one drug for which they carried a high-risk variant, and for which international guidelines recommend a change of drug or dosage. Our analysis confirms the high prevalence of actionable pharmacogenetic variants in the Swiss population. It also shows that a substantial minority of patients are exposed to drugs for which they carry potentially problematic variants. Implementing a genetically informed approach to drug prescribing could have a positive impact on the quality of healthcare delivery.

Effectiveness of Aerobic Training for Adverse Symptoms Related to Chemotherapy During Treatment: Protocol for a Randomized Controlled Trial With Cost-Effectiveness Assessment.

BACKGROUND: One strategy to prevent adverse effects resulting from chemotherapy treatment is to perform physical exercises during treatment. However, there is still no consensus on the best type and intensity of exercise, nor when it should be started. Most studies have been carried out in patients with breast cancer, usually a few weeks after starting chemotherapy, on an outpatient basis 2 to 3 times a week. The main differences in our study are that we carried out physical training in hospitalized patients undergoing a cycle of chemotherapy for cancer treatment and that this training was carried out 5 times a week and was not restricted to a specific type of cancer. OBJECTIVE: We aimed to evaluate the effects of aerobic training on symptoms related to chemotherapy (nausea, vomiting, asthenia, and sensation of weakness), fatigue, mobility, clinical complications, and length of hospital stay of patients during the drug treatment cycle. We also evaluated patient satisfaction with the proposed intervention, the adverse effects of aerobics training, and the cost-effectiveness of this intervention. METHODS: This is a controlled and randomized trial with blinded evaluation that will include 94 hospitalized patients with cancer for 1 or more cycles of chemotherapy. The intervention group will perform aerobic training during a cycle of chemotherapy. The control group will receive a booklet with guidelines for staying active during the hospitalization period. The groups will be compared using a linear mixed model for fatigue, mobility, and chemotherapy-related symptoms before and after the intervention. The length of hospital stay will also be compared between groups using Kaplan-Meier survival analysis. The incidence of complications will be compared using the χ2 test. Cost-effectiveness and cost-utility analyses will be performed for the impact of exercise and quality-adjusted life years with the EQ-5D-3L-21 quality of life trials. The implementation variables (acceptability, suitability, and feasibility) will be evaluated by frequencies. RESULTS: The clinical trial registration was approved in March 2023. Recruitment and data collection for the trial are ongoing, and the results of this study are likely to be published in late 2025. CONCLUSIONS: Chemotherapy has side effects that negatively impact the quality of life of patients with cancer. Aerobic exercise can reduce these side effects in a simple and inexpensive way. The field of work of physical therapists could be expanded to oncology if the intervention works. TRIAL REGISTRATION: Registro Brasileiro de Ensaios Clínicos RBR-6b4zwx3; https://tinyurl.com/39c4c7wz. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/60828.

Drug related adverse event assessment in neonates in clinical trials and clinical care.

INTRODUCTION: Assessment of drug-related adverse events is essential to fully understand the benefit-risk balance of any drug exposure, weighing efficacy versus safety. This is needed for both drug labeling and clinical decision-making. Assessment is based on seriousness, severity and causality, be it more difficult to apply in neonates. Adverse event detection or prevention in the neonatal clinical setting is also more complicated because of polypharmacy, and off-label or unlicensed pharmacotherapy. AREAS COVERED: Tools became available to assess severity and causality of adverse events in neonates recruited in clinical trials. The first version of the Neonatal Adverse Event severity score (NAESS) reduced the inter-observer variability. Causality tools like the Naranjo score were also tailored to neonates. These tools are also instrumental to support proactive pharmacovigilance in clinical care, while multidisciplinary care teams and computerized pharmacovigilance using advanced data analysis, like machine learning are emerging approaches to develop effective decision strategies. EXPERT OPINION: All stakeholders involved in development of medicines or its clinical use should be aware of the limitations of the currently available assessment tools. Extension and optimization of these tools, advanced data analysis approaches, and capturing the variability in time-dependent physiology are warranted to improve pharmacovigilance in neonates.

Studying the Impact of European Union Regulatory Interventions for Minimising Risks From Medicines: Lessons Learnt and Recommendations.

PURPOSE: The European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) launched a strategy to examine the public health impact of major regulatory interventions aimed at minimising risks of medicinal products. We conducted a lessons learnt analysis of impact studies completed between 2015 and 2023. METHODS: We surveyed PRAC Sponsors and (Co-)Rapporteurs involved in the evaluation of 12 impact studies (10 commissioned by EMA and 2 conducted collaboratively by Member States) to explore how these support regulatory decision-making. Questions covered achievement of study objectives, risk minimisation effectiveness, added value for regulatory decision-making, and recommendations for future impact studies. Themes were generated using thematic content analysis. RESULTS: Survey responses from 15 PRAC Sponsors and (Co-)Rapporteurs from 10 European Union Member States were included in the analysis. Among four cross-sectional surveys and eight drug utilisation studies, 50% achieved all objectives, the other studies partially due to limitations. Two studies concluded that risk minimisation measures were overall effective, two were effective with variation across countries, two were partially effective and four studies showed limited effectiveness. Two studies were deemed inconclusive due to limitations. The reasons for the limited effectiveness of risk minimisation may be explored using mixed-method approaches. Assessment of study feasibility and a priori discussion of effectiveness measurements is important. CONCLUSION: Despite limitations, impact research adds value to regulatory decision-making by addressing knowledge gaps and providing additional information on unintended consequences of regulatory interventions. Our recommendations will help to improve planning, conducting and interpretating future impact studies.

Public perspective on potential treatment intervention harm in clinical trials-terminology and communication.

BACKGROUND: Randomised controlled trials (RCTs) are typically designed to determine beneficial intervention effects. In addition, an important aspect of every trial is to collect data on any potential harmful effects, with the aim of ensuring that the benefit-risk balance is appropriate. The language used by trialists to describe these potential harmful effects is inconsistent. In pharmacological trials, researchers collect adverse events; when a causal relationship is suspected adverse events are further classified as adverse reactions. Academic researchers have moved to collectively refer to these as harm outcomes; the pharmaceutical industry refer to these events as safety outcomes. In trials of complex interventions, phrases such as unintended consequences or effects are used. With the inconsistent use of terminology by researchers and the potential benefits to be gained from harmonising communications, we sought public opinion on terminology used to describe harmful effects and how these outcomes are communicated in the scientific literature, as well as in public facing material on medications. METHODS: We held two in-person public involvement meetings with public partners, in London and Aberdeen in 2023. Both meetings followed a pre-specified format. We provided a background to the topic including the information researchers collect on potential harms in clinical trials and shared examples on how this information gets presented in practice. We then discussed public partners' perspectives on terminology used and communication of intervention harm in academic journals and in public facing materials. A summary of these discussions and the main topics raised by public partners are presented. RESULTS: Public partners endorsed the use of different terms for different situations, preferring the use of 'side-effect' across all contexts and reserving the use of 'harm' to indicate more severe events. Generally, public partners were happy with the type of information presented in public facing materials but discussions revealed that presentation of information on public NHS websites led to misconceptions about harm. CONCLUSION: This work provides a starting point on preferred terminology by patients and the public to describe potential harmful intervention effects. Whilst researchers have tried to seek agreement, public partners endorsed use of different terms for different situations. We highlight some key areas for improvement in public facing materials that are necessary to avoid miscommunication and incorrect perception of harm.

A machine learning technology for addressing medication-related risk in older, multimorbid patients.

OBJECTIVES: To evaluate the FeelBetter machine learning system's ability to accurately identify older patients with multimorbidity at Brigham and Women's Hospital at highest risk of medication-associated emergency department (ED) visits and hospitalizations, and to assess the system's ability to provide accurate medication recommendations for these patients. STUDY DESIGN: Retrospective cohort study. METHODS: The system uses medications, demographics, diagnoses, laboratory results, health care utilization patterns, and costs to stratify patients' risk of ED visits and hospitalizations. Patients were assigned 1 of 22 risk levels based on their system-generated risk percentile of either ED visits or hospitalizations. Logistic regression models were used to estimate the odds of ED visits and hospitalizations associated with each successive risk level compared with the 45th to 50th percentiles. After stratification, 100 high-risk (95th-100th percentiles) and 100 medium-risk (45th-55th percentiles) patients were randomly selected for generation of medication recommendations. Two clinical pharmacists reviewed the system-generated medication recommendations for these patients. RESULTS: Logistic regression models predicting 3-month utilization showed that compared with the 45th to 50th percentiles, patients in the top 1% risk percentile had ORs of 7.9 and 17.3 for ED visits and hospitalizations, respectively. The first 5 high-priority medications on each patient's medication list were associated with a mean (SD) of 6.65 (4.09) warnings. Of 1290 warnings reviewed, 1151 (89.2%) were assessed as correct. CONCLUSIONS: The FeelBetter system effectively stratifies older patients with multimorbidity at risk of ED use and hospitalizations. Medication recommendations provided by the system are largely accurate and can potentially be beneficial for patient care.

Quantitative Measurement of the Direct Public Health Impact of Medicines Withdrawals in Europe: Development of a Modelling Method and Proof-of-Concept Study to Estimate the Morbidity and Mortality Prevented by Regulatory Action.

PURPOSE: Removing medicines from market may benefit public health by preventing adverse drug reactions (ADRs), which should be quantified. This study's aim was to identify a model to quantify the impact of medicines' marketing authorisation (MA) withdrawal and revocation in terms of preventing morbidity and mortality. METHODS: MA withdrawals and revocations for safety reasons in France, Germany and/or the United Kingdom between July 2012 and December 2016 were identified for prescription medicines. Annual exposure was estimated for each medicine, using IQVIA Medical Research Data (IMRD)-France, IMRD-Germany and IMRD-UK primary care electronic health record databases. European Medicines Agency records provided reasons for regulatory action for each medicine. Absolute risks of ADRs which led to MA withdrawal were estimated for patients exposed to each medicine by systematic review of quantitative research. Public health impact, expressed as annual number of ADRs avoided, was estimated by modelling exposure and ADR risk. RESULTS: Four MA withdrawals and two revocations met study inclusion criteria. Each product's usage decreased following MA withdrawal or revocation. Absolute risk for ADRs was 0.1%-41.25%. To estimate impact of each withdrawal or revocation, its average annual exposure within each IMRD population was multiplied by the absolute risk to give the crude number of ADRs prevented annually due to regulatory action. CONCLUSIONS: This model quantifies the public health impact of MA withdrawal and revocation in terms of serious morbidity, resulting from eliminated or reduced usage of medicines. This method can be applied to products in other settings to quantify the impact of other pharmacovigilance actions.

Medication reviews by emergency department pharmacists in patients hospitalised for an adverse drug event: a cost study.

OBJECTIVE: To perform a cost study of pharmacist-led medication reviews in patients with an acute hospitalization for adverse drug events. METHOD: Emergency department pharmacists performed medication reviews in patients hospitalized after visiting the emergency department for an adverse drug event (ADE). Control patients were hospitalized after an emergency department visit not related to an ADE and received usual care. The costs of the intervention were labour costs of the junior emergency department pharmacist and the cost savings consisted of costs of medication that was stopped or reduced during six months after the intervention. Sensitivity analyses were performed to evaluate different scenarios. RESULTS: In the intervention group (n = 104) 113 medication changes led to stopping or reducing medication, accounting for averted costs of €22,850. In the control group (n = 112) 39 medication changes led to stopping or reducing medication, accounting for averted costs of €299. The mean labour costs of the intervention were €138 per patient, resulting in saved costs of €61 per patient per six months. Sensitivity analyses showed that if the intervention would be performed by a senior clinical pharmacist, there are no cost savings (€-21), if parts of the intervention would be executed by pharmacy technicians (e.g. administrative tasks), cost savings would be augmented to €87, if outliers in costs associated with medication reduction would be excluded, there are no cost savings (€-35) and if the costs of reduced medication were extrapolated to one year, cost savings would be €260. CONCLUSION: In this study, medication reviews by junior emergency department pharmacists in patients hospitalized after an emergency department visit for an ADE lead to a cost reduction over a six month period. TRIAL REGISTRATION: The main study is registered on the ISRCTN registry with trial ID ISRCTN12506329 on 06-03-2022.

Preventing Prescribing Cascades: Ensuring Medication Safety for Older Adults.

PURPOSE: To define prescribing cascades (PCs) and provide tools to identify PCs, including the most common PCs described in the literature. PCs lead to the accumulation of medications prescribed to older adults, disproportionately affecting those who often have additional health care complexities, such as multiple chronic conditions and multiple transitions of care. METHOD: Review of recent research efforts to identify and describe evolving clinical practice interventions to detect and reverse PCs. RESULTS: Clinicians can contribute to mitigating PCs through better understanding of how PCs occur in practice. Armed with this knowledge, clinical team members can implement proposed strategies and techniques to engage in primary and secondary prevention of PCs. CONCLUSION: Ultimately, PCs are a culprit of preventable medication harm. Several tools are presented, which are initiated through maintaining a high index of suspicion for PCs in the evaluation of a new symptom presentation by older patients. [Journal of Gerontological Nursing, 50(9), 7-11.].

Changing Gadolinium-Based Contrast Agents to Prevent Recurrent Acute Adverse Drug Reactions: 6-Year Cohort Study Using Propensity Score Matching.

OBJECTIVE: To determine the preventive effect of changing gadolinium-based contrast agents (GBCAs) to reduce the recurrence of GBCA-associated acute adverse drug reactions (ADRs). MATERIALS AND METHODS: This retrospective, observational, single-center study-conducted between January 2016 and December 2021-included 238743 consecutive GBCA-enhanced MRI examinations. We focused on a subgroup of patients who experienced acute GBCA-associated ADRs during any of these examinations and subsequently underwent follow-up GBCA-enhanced MRI examinations up until July 2023. The follow-up examinations involved either the same (non-change group) or different (change group) GBCAs compared to the ones that initially caused the acute ADR. Baseline participant characteristics, generic profile of the GBCAs, administration of premedication, history of prior ADR to iodinated contrast media, and symptoms of GBCA-associated acute ADRs were retrospectively analyzed. Multivariable logistic regression with generalized estimating equations and propensity score matching were used. RESULTS: A total of 1042 instances of acute ADRs (0.44%; 95% confidence interval [CI]: 0.41%-0.46%) were reported. Three-hundred and seventy-three patients underwent GBCA-enhanced MRI examinations after experiencing GBCA-associated acute ADRs within the study period; 31.9% (119/373) reexperienced acute ADRs at any of the follow-up examinations. The ADR recurrence was significantly lower in the GBCA change group than in the non-change group according to multivariable logistic regression (adjusted odds ratio [OR]: 0.35; 95% CI: 0.13-0.90; P = 0.03) and analysis with propensity score matching (14.3% [6/42] vs. 36.9% [31/84], respectively; OR: 0.32, 95% CI: 0.11-0.94; P = 0.04). A history of an ADR to iodinated contrast media (OR: 1.14, 95% CI: 0.68-1.90; P = 0.62) and premedication (adjusted OR: 2.09, 95% CI: 0.93-4.68; P = 0.07) were not significantly associated with GBCA-associated acute ADR recurrence. A separate analysis for recurrent allergic-like hypersensitivity reactions demonstrated similar results (adjusted OR: 0.20, 95% CI: 0.06-0.65; P < 0.01). CONCLUSION: Changing GBCAs may reduce the risk of GBCA-associated acute ADR recurrence.

Frequency, Characteristics, and Preventability of Adverse Drug Reactions in Perioperative Neurosurgery: Analysis Over 11 Years.

OBJECTIVE: Despite the importance of adverse drug reactions (ADRs), little is known about their role in perioperative neurosurgery. This study aimed to determine the prevalence of ADRs in perioperative neurosurgery and clarify the characteristics, severity, preventability, and risk factors of ADRs. METHODS: Data for all patients who underwent neurosurgical procedures over an 11-year period were analyzed. During the study period, 3648 surgical procedures were performed for 2695 patients. Demographic and clinical information documented included medical history, allergic history, diagnosis, surgical method, suspected drugs, concomitant medications, and drug details. Multivariate logistic regression analyses were performed to identify independent parameters that were correlated with ADRs. RESULTS: In total, 467 ADRs (18.3% ADRs/all neurosurgical procedures) were experienced by 401 patients. Anticonvulsants were associated with the highest number of ADRs (16.0%), followed by antibiotics (14.7%). Patients with ADRs were older than patients without ADRs (P < 0.01). The total number of drugs in patients with ADRs was 8.8 ± 3.6, compared to 5.2 ± 2.4 for patients without ADRs (P < 0.01). There were no significant differences in sex, allergic history, severe renal dysfunction (estimated glomerular filtration rate < 30 ml/min/1.73 m2), hypertension, diabetes, urgency of surgery, and type of surgery. Multivariate analysis showed that a high total number of drugs (odds ratio=3.2; 95% confidence interval 1.9-5.1) and older age (odds ratio=2.1; 95% confidence interval 1.3-3.8) were independent risk factors for ADRs. CONCLUSIONS: The frequency of suspected and severe ADRs was higher than expected. Polypharmacy and older age were independent risk factors for ADRs in perioperative neurosurgery. To decrease ADRs during perioperative neurosurgery, polypharmacy must be discouraged, especially among older adult patients.

Improved Patient Engagement and Cost Savings Through a Novel Medication Review Process.

Pharmacist-led interventions are pivotal in identifying and resolving potential adverse drug events (pADEs) while enhancing blood pressure control and medication adherence through educational and counseling interventions. This practice brief outlines the outcomes of the Blue Bag Initiative (BBI), which enhanced pharmacist-led comprehensive medication reviews (CMRs) across community pharmacies in Virginia under Center for Disease Control Cooperative Agreement NU58DP006535. BBI yielded a rate of 131.6 pADEs identified per 100 participants and demonstrated cost savings of 1 to 3 million dollars for the health care system. This report underscores the significance of a standardized, pharmacist-led CMR as integral to interdisciplinary team-based care models within physician practices, facilitating medication therapy management implementation. Enhanced CMR can improve cardiovascular health outcomes while reducing health care expenditures by augmenting patient engagement and medication adherence. This study thus highlights the efficacy and potential of pharmacist-led interventions in increasing access to and optimizing patient care.

Cost avoidance of pharmacist-led deprescribing using STOPPFrail for older adults in nursing homes.

BACKGROUND: The Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy (STOPPFrail) criteria aim to reduce inappropriate/unnecessary medications in frail older adults, which should minimise adverse drug events and additional healthcare expenditure. Little is known about the economic outcomes of applying these criteria as an intervention. AIM: To evaluate cost avoidance of pharmacist-led application of STOPPFrail to frail older nursing home residents with limited life expectancy. METHOD: Pharmacist-identified STOPPFrail-defined potentially inappropriate medications that were deprescribed by patients' general practitioners were assigned a rating by a multidisciplinary panel, i.e. the probability of an adverse drug event occurring if the medication was not deprescribed. The intervention's net cost benefit and cost-benefit ratio were then determined by factoring in adverse drug event cost avoidance (calculated from probability of adverse drug event ratings), direct cost savings (deprescribed medication costs/reimbursement fees), and healthcare professionals' salaries. RESULTS: Of the 176 potentially inappropriate medications deprescribed across 69 patients, 65 (36.9%) were rated as having a medium or high probability of an adverse drug event occurring if not deprescribed. With €27,162 for direct cost savings, €61,336 for adverse drug event cost avoidance, and €2,589 for healthcare professionals' salary costs, there was a net cost benefit of €85,909 overall. The cost-benefit ratio was 33.2 and remained positive in all scenarios in sensitivity analyses. CONCLUSION: Pharmacist-led application of STOPPFrail to frail older nursing home residents is associated with significant cost avoidance. Wider implementation of pharmacist interventions in frail older nursing home residents should be considered to reduce potentially inappropriate medications and patient harm, alongside substantial cost savings for healthcare systems.

The STAR Compass to Guide Future Pharmacovigilance Based on a 10-Year Review of the Strengthened EU System.

This article reflects on the 2010 pharmacovigilance legislation of the European Union (EU). Its legislative aim of better patient and public health protection through new responsibilities for pharmaceutical companies and regulatory bodies is considered to have been achieved and is well supported by the good pharmacovigilance practices 'EU-GVP'. For future progress, we set out a vision for high-quality pharmacovigilance in a world of ongoing medical, technological and social changes. To deliver this vision, four principles are proposed to guide actions for further progressing the EU pharmacovigilance system: synergistic interactions with healthcare systems; trustworthy evidence for regulatory decisions; adaptive process efficiency; and readiness for emergency situations (the 'STAR principles'). Like a compass, these principles should guide actions for building capacity, technology and methods; improving regulatory processes; and expanding policies, frameworks and research agendas. Fit for the future, the EU system should achieve further improved outputs in terms of safe, effective and trusted use of medicines and positive health outcomes within patient-centred healthcare.

The PrescIT platform: An interoperable Clinical Decision Support System for ePrescription to Prevent Adverse Drug Reactions and Drug-Drug Interactions.

INTRODUCTION: Preventable medication errors have been proven to cause significant public health burden, and ePrescription is a key part of the process where medication errors and adverse effects could be prevented. Information systems and "intelligent" computational approaches could provide a valuable tool to prevent such errors with profound impact in clinical practice. OBJECTIVES: The PrescIT platform is a Clinical Decision Support System (CDSS) that aims to facilitate the prevention of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) in the phase of ePrescription in Greece. The proposed platform could be relatively easily localized for use in other contexts too. METHODS: The PrescIT platform is based on the use of Knowledge Engineering (ΚΕ) approaches, i.e., the use of Ontologies and Knowledge Graphs (KGs) developed upon openly available data sources. Open standards (i.e., RDF, OWL, SPARQL) are used for the development of the platform enabling the integration with already existing IT systems or for standalone use. The main KG is based on the use of DrugBank, MedDRA, SemMedDB and OpenPVSignal. In addition, the Business Process Management Notation (BPMN) has been used to model long-term therapeutic protocols used during the ePrescription process. Finally, the produced software has been pilot tested in three hospitals by 18 clinical professionals via in-person think-aloud sessions. RESULTS: The PrescIT platform has been successfully integrated in a transparent fashion in a proprietary Hospital Information System (HIS), and it has also been used as a standalone application. Furthermore, it has been successfully integrated with the Greek National ePrescription system. During the pilot phase, one psychiatric therapeutic protocol was used as a testbed to collect end-users' feedback. Summarizing the feedback from the end-users, they have generally acknowledged the usefulness of such a system while also identifying some challenges in terms of usability and the overall user experience. CONCLUSIONS: The PrescIT platform has been successfully deployed and piloted in real-world environments to evaluate its ability to support safer medication prescriptions.