Using machine learning or deep learning models in a hospital setting to detect inappropriate prescriptions: a systematic review.

OBJECTIVES: The emergence of artificial intelligence (AI) is catching the interest of hospital pharmacists. A massive collection of health data is now available to train AI models and hold the promise of disrupting codes and practices. The objective of this systematic review was to examine the state of the art of machine learning or deep learning models that detect inappropriate hospital medication orders. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. MEDLINE and Embase databases were searched from inception to May 2023. Studies were included if they reported and described an AI model intended for use by clinical pharmacists in hospitals. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). RESULTS: 13 articles were selected after review: 12 studies were judged to have high risk of bias; 11 studies were published between 2020 and 2023; 8 were conducted in North America and Asia; 6 analysed orders and detected inappropriate prescriptions according to patient profiles and medication orders; and 7 detected specific inappropriate prescriptions, such as detecting antibiotic resistance, dosage abnormality in prescriptions, high alert drugs errors from prescriptions or predicting the risk of adverse drug events. Various AI models were used, mainly supervised learning techniques. The training datasets used were very heterogeneous; the length of study varied from 2 weeks to 7 years and the number of prescription orders analysed went from 31 to 5 804 192. CONCLUSIONS: This systematic review points out that, to date, few original research studies report AI tools based on machine or deep learning in the field of hospital clinical pharmacy. However, these original articles, while preliminary, highlighted the potential value of integrating AI into clinical hospital pharmacy practice.

Medication adherence and persistence among patients with non-small cell lung cancer receiving tyrosine kinase inhibitors and estimation of the economic burden associated with the unused medicines.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths. Its treatment includes specific oral tyrosine kinases inhibitors (TKIs). OBJECTIVES: To estimate adherence and persistence among patients receiving TKIs and to assess the economic burden of the unused medicines in Alsace (France). METHOD: This retrospective study was carried out using the Insurance Healthcare database. MAIN OUTCOME MEASURES: Adherence was calculated using medication possession ratio (MPR), persistence using estimated level of persistence with therapy (ELPT) and economic impact using prescription refill data. RESULTS: 242 patients were receiving TKIs. The most common TKIs prescribed were erlotinib (75.6%, n = 183) and crizotinib (12.8%, n = 31). Total of 149 patients were included in the adherence analysis. Overall MPR was 0.98. 180 patients were included in the persistence analysis. Almost half of patients had stopped treatment at 60 days and only 38.3% (n = 69) were still persistent with the therapy at 120 days. The expenses related to unused TKIs amounted to €356,392 and were related majorly to treatment discontinuation followed by overlapping refills, patient deaths and dose- or drug-switching, respectively. CONCLUSIONS: Our data indicated overall adherence medicines above the acceptable limit of 0.80 but also pointed out a significant decline in persistence over time. The resulting economic losses justify the need for physicians and pharmacists to closely monitor their patients to ensure continuity of treatment. To limit the cost associated with unused medicines, interventions such as app-based monitoring, dispensing TKIs per unit over shorter periods and not only on monthly intervals could be implemented.

Adherence to oral anticancer chemotherapies and estimation of the economic burden associated with unused medicines.

Background The list of oral and expensive chemotherapy agents has lengthened over the last few years and has created unique medication adherence concerns. In a real-life setting, patients often do not take their medications as prescribed. This pattern is associated with poor outcomes and increased health care costs. Objectives To estimate the adherence to oral anticancer chemotherapies and to determine the economic burden of unused medicines due to patients' death. Setting Alsace (France). Method This retrospective study was carried out by using ERASME, an Insurance Healthcare database. Main outcome measures Adherence was calculated using medication possession ratio and economic impact using prescription refill data. Results 10,734 patients were treated with oral anticancer medicines (cytotoxic agents, hormonal and targeted therapies). Averaged adherence of 0.86 was observed although it varied significantly between subclasses (cytotoxic agents: 0.69 ± 0.14, hormonal therapy: 0.91 ± 0.17 and targeted therapy: 0.79 ± 0.17). 1631 patients died during the study period. The expenses related to unused chemotherapies amounted to €152,175. Conclusions Our data showed that overall adherence to oral anticancer medicines was above the acceptable limit of adherence of 80% with a marked graduation in values between cytotoxic agents, hormonal and targeted therapies. These statistical significant differences in medication possession ratio could be related to the intrinsic toxicity of the three subclasses of molecules, their tolerance and adverse effects. To limit the cost associated with unused medicines, interventions such as dispensing expensive oral anticancer chemotherapies per unit over shorter periods and not only on monthly intervals could be implement.

Patients' information and perspectives on biosimilars in rheumatology: A French nation-wide survey.

OBJECTIVE: To assess the patients' information about biosimilars and to identify the patients' incentives and deterrents to concur with the use of biosimilars. METHODS: Nation-wide cross-sectional study assessing information and concerns about biosimilars of French patients treated for rheumatic inflammatory diseases, whether they were treated or not by a biological DMARD. The assessment was available online from March to July 2017. RESULTS: Among the 629 respondents, 43% knew what biosimilars were. The main sources of information were rheumatologists and patient associations. Among patients treated with a biosimilar, 44% were not informed before they received the treatment. The patients' concerns focused on the non-similar molecular structure (46%), efficacy (60%) and safety (57%) comparatively to the originator biologic. 15% of respondents would refuse to switch their biologic to its biosimilar. More than 50% of respondents would warily accept to switch medications and interrupt the treatment if in doubt. Being informed about biosimilars and a good understanding of the definition of biosimilars were characteristics associated with better adherence to biosimilars. The rheumatologist was considered the most influent source of information about biosimilars and was considered reliable when deciding to switch a biologic to its biosimilar. Patient were reluctant to substitution of the medications by pharmacists (2%). Medico-economical issues acted as an incentive and a deterrent to accept the switch of medication. CONCLUSION: Biosimilars are largely unknown to patients. Information seems to be instrumental in improving the patients' adherence to biosimilars and could help preserving the therapeutic relationship and avoiding a nocebo effect.

Policies for biosimilar uptake in Europe: An overview.

BACKGROUND: Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe. OBJECTIVES: The aim of this article is to provide an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake. METHODS: An overview of policies on biosimilars was obtained via a questionnaire, supplemented with relevant articles. Topics were organized in five themes: availability, pricing, reimbursement, demand-side policies, and recommendations to enhance uptake. RESULTS: In all countries studied, biological medicines are available. Restrictions are mainly dependent on local organization of the healthcare system. Countries are willing to include biosimilars for reimbursement, but for commercial reasons they are not always marketed. In two thirds of countries, originator and biosimilar products may be subjected to internal reference pricing systems. Few countries have implemented specific incentives targeting physicians. Several countries are implementing pharmacist substitution; however, the scope and rules governing such substitution tend to vary between these countries. Reported educational policies tend to target primarily physicians, whereas fewer initiatives were reported for patients. Recommendations as proposed by the different country experts ranged from the need for information and communication on biosimilars to competitive pricing, more support for switching and guidance on substitution. CONCLUSIONS: Most countries have put in place specific supply-side policies for promoting access to biosimilars. To supplement these measures, we propose that investments should be made to clearly communicate on biosimilars and educate stakeholders. Especially physicians need to be informed on the entry and use of biosimilars in order to create trust. When physicians are well-informed on the treatment options, further incentives should be offered to prescribe biosimilars. Gainsharing can be used as an incentive to prescribe, dispense or use biosimilars. This approach, in combination with binding quota, may support a sustainable biosimilar market.

Knowledge, behaviors and practices of community and hospital pharmacists towards biosimilar medicines: Results of a French web-based survey.

This study's aims were: 1) to extract a comprehensive overview of the knowledge, experience and opinions of both community pharmacists and hospital pharmacists regarding biosimilar medicines in France; and 2) to identify the perceived problems and solutions to promoting their prescription. A 2015 web-based survey was conducted by the Observatoire des Médicaments, des Dispositifs Médicaux et de l'Innovation Thérapeutique of Alsace. A total of 802 pharmacists responded to the survey. Many (536, 66.8%, [95% confidence interval (CI) 63.6-70.1]) indicated that they were not familiar with biosimilars. Half of community pharmacists (95% CI 42.7-57.3) stated that they were not at all informed about biosimilar drugs, compared with 15.7% (95% CI 12.9-18.6) of hospital pharmacists. Almost all respondents (781, 97.4%, [95% CI 96.3-98.5]) had at least one pending question on biosimilars. Most of the questions were related to the manufacturing process, safety, substitution rules and the international non-proprietary name prescription. At the time of the study, 467 pharmacists (58.2%, [95% CI 54.8-61.6]) had already validated a prescription for a biosimilar drug, mainly for filgrastim. These latter were more comfortable in explaining the benefit of biosimilar medicines to the patient. Pharmacists were rather favorable to biosimilar drugs, and about 9 of 10 quoted healthcare cost savings as incentives to their prescription. However, many did not agree with allowing biosimilar substitution. "Patients' wishes to be treated with the originator" and "indication extrapolation" were the two main constraints identified. The survey highlighted the need to provide French pharmacists with accurate and comprehensive information regarding biosimilar medicines.

Rheumatologists' Perceptions of Biosimilar Medicines Prescription: Findings from a French Web-Based Survey.

BACKGROUND: Healthcare cost savings are closely linked to prescribers' confidence in and acceptance of the prescription of biosimilar drugs. OBJECTIVES: The aim of this study was to assess the knowledge, experience and opinions of hospital-based and office-based French rheumatologists with regard to biosimilar medicines and to identify the barriers to and possible options to promote their prescription. METHODS: A web-based, self-administered survey was conducted among French rheumatologists from June 8 to August 2, 2015. RESULTS: A total of 116 rheumatologists responded to the survey. Many reported having little knowledge and a lack of available information about biosimilar drugs, especially office-based rheumatologists. 98.3% of the respondents had at least one question about biosimilars, and seven in ten raised issues regarding substitution, iatrogenic effects or cost savings that might be achievable. Only eight rheumatologists had already prescribed a biosimilar drug. The most common barriers reported were indication extrapolation and a lack of data about tolerability. Nine out of ten physicians thought that starting a treatment with a biosimilar drug in biologic treatment-naïve patients was possible. The rheumatologists' opinions were rather favorable towards the implementation of biosimilars, but a majority expressed a negative opinion about substitution by the pharmacist. CONCLUSIONS: Our survey gave a better appreciation of the concerns associated with biosimilar prescriptions. Targeted communication initiatives, deeper experience and availability of new clinical data may help to address the outstanding questions and should overcome the misunderstandings surrounding biosimilar drugs among rheumatologists.

Drug-dispensing problems community pharmacists face when patients are discharged from hospitals: a study about 537 prescriptions in Alsace.

OBJECTIVES: To identify both type and frequency of the challenges community pharmacists face when dispensing drugs from hospital discharge prescriptions, to describe the measures undertaken to resolve the issues at stake and to list their consequences. DESIGN: We carried out an observational study in the community pharmacies of the French region of Alsace and asked the community pharmacy staff to review 537 hospital discharge prescriptions in 2013 using anonymous data collection forms. SETTING AND PARTICIPANTS: Nineteen community pharmacies. MAIN OUTCOME MEASURES: Number of patients informed about their medication (at hospital and/or community pharmacy), type and frequency of issues encountered during drug dispensing, type and frequency of measures undertaken to resolve the issues, type and frequency of the consequences regarding drug dispensing. RESULTS: Community pharmacists faced 165 challenges from 145 hospital discharge prescriptions (i.e. 27.5% out of 528 analysed prescriptions), mostly correlated to the quality of the prescriptions (n = 100, 60.6%) or to logistical matters (n = 54, 32.7%). A mere 36.8% of the patients received information pertaining to their medication while being hospitalized. Of note, 40.5% of the prescriptions were delivered to pharmacies within 2 days following the patients' discharge. In order to resolve the different issues preventing drugs from being dispensed (n = 33/145 prescriptions), pharmacists sought information, mainly from patients, colleagues and hospital prescribers. The pharmacists were able to dispense all the drugs prescribed in 138 out of 145 cases (95.2%). CONCLUSIONS: This study highlighted the challenges encountered by community pharmacists and their significant contribution to the continuity of care upon patients being discharged from hospitals.

A UV-Raman spectrometry method for quality control of anticancer preparations: Results after 18 months of implementation in hospital pharmacy.

In France, chemotherapy preparation units of hospital pharmacy compound cytotoxic infusion bags adapted to each patient. The narrow therapeutic index of these preparations led us to implement qualitative and quantitative control for patients' safety. To this aim, we calibrated an equipment combining UV-vis spectrometry and Raman spectroscopy (QC Prep+) and monitored 14 different molecule-solvent combinations over a 18 months period. This rapid and specific method allowed the qualitative and quantitative analysis of 1 mL sample tests in less than 2 min. On 5742 anticancer preparations, we obtained accepted results with more than 99.4% solvent identification, 99.6% drug identification and only 1.52% of preparations not matching quantitative specifications (±15% of theoretical concentration). This quantitative control enabled us to pinpoint some critical points of production for two of the most common preparations. We thus updated the procedures of reconstitution and preparation, increasing the quality of final product. UV-Raman spectrometry is thus an effective tool to control chemotherapy infusions and to improve good practices of preparation.

Analysis and Breakdown of Overall 1-Year Costs Relative to Inpatient and Outpatient Care Among Rheumatoid Arthritis Patients Treated with Biotherapies Using Health Insurance Claims Database in Alsace.

BACKGROUND: The economic burden linked to rheumatoid arthritis (RA) has greatly increased since the inclusion of biotherapies in the therapeutic arsenal. OBJECTIVES: This study aimed first to look at the breakdown of the rheumatoid arthritis patients on biotherapy in Alsace, France, in 2012, then to evaluate the annual cost per treated patient for each management pathway: inpatient care with intravenous biotherapies and/or outpatient care through the use of subcutaneous drugs, and finally to conduct a cost comparison with a focus on infliximab, adalimumab and etanercept. METHODS: This observational study was conducted in Alsace using 2012 health claims data from the DCIR (Données de Consommation Inter Régime) and PMSI (Programme de Médicalisation des Systèmes d'Information) databases, taking into account direct medical and non-medical costs in a real-life setting and from a National Health Insurance perspective. RESULTS: There were 5702 RA patients, i.e. 0.31 % of the Alsace population in 2012, including 1075 subjects (18.85 %) receiving biotherapy treatment. The most frequently prescribed biotherapies were etanercept and adalimumab. The estimated overall cost of care of these 5702 patients was €30.3 million, with about 50 % for the care of the 18.85 % patients on biotherapy. Average costs for inpatient, outpatient and mixed care ranged from €14,197 to €16,873 per patient per year. Annual average cost for management of a single RA patient with infliximab was significantly higher than with adalimumab and etanercept: €16,480 versus €14,116 and €14,338, respectively. CONCLUSION: These findings confirm the trends of initial modelling approaches and quantify the cost difference between various biotherapy management pathways.