[Drug dispensation at both community and hospital pharmacy, the highly active antiretrovirals example]. / Le double circuit de dispensation, exemple des traitements antirétroviraux : quelle pertinence ?

OBJECTIVES: Highly active antiretroviral therapies against the human immunodeficiency virus are available for patients in France in community pharmacy or in hospital pharmacy. More than 20 years after the implementation of the dual delivery system, it seems necessary to question the relevance of the dual dispensing circuit both in terms of service provided to patients and expenditure for health insurance. METHODS: The health insurance files were used to quantify the delivery of antiretrovirals therapies in the community pharmacy and in the hospital pharmacy. A survey was performed involving patients to find out their point of view on dispensing in hospital pharmacy and were the patients came from. The differential cost from the health insurance point of view between the two delivery system was calculated on the basis of the quantities delivered and the purchase prices at the hospital center in 2018. RESULTS: More than 80% of the quantities of antiretrovirals therapies are now delivered by community pharmacies. The arguments in favor of the antiretrovirals therapies dispensation by hospital pharmacy forwarded by patients are the anonymity and constant medicines availability. Health insurance is required to refund a drug at different prices depending on the delivery place, for about 37€ per box in favour of hospital dispensing. CONCLUSION: This study presents a complete inventory of the dual delivery system for antiretroviral therapies. Hospital and community therefore remain complementary to welcome outptients who will seek different delivery methods there. Little known to patients and professionals, this dual delivery system generates complexities at the stages of prescription, dispensing and reimbursement. It only concerns a minority of patients and its benefit for health insurance seems uncertain.

[Funding of psychiatry in France, the problem of expensive drugs. Example of Esketamine in the case of resistant depressive episodes]. / Financement de la psychiatrie en France, la question des médicaments onéreux : exemple de l'Esketamine dans l'épisode dépressif caractérisé résistant.

In France, the funding of mental health institutions relies on an annual budget allocation. Esketamine, a non-competitive NMDA glutamate receptor antagonist, has been approved for adults with treatment-resistant major depressive disorder since 2019. However, due to its high cost (€200 per 28 mg device, excluding tax), the aim of this work was to evaluate whether the income received by an institution for the management of a patient treated with Esketamine could cover the purchase of devices, based on real clinical data. Within our institution, seven patients underwent treatment with Esketamine during the study period resulting in a total usage of 714 devices, amounting to a purchase cost of €142,800. Over the course of the follow-up period, the institution received €149,054 in revenue for the treatment of these patients. Our analysis reveals that the expense associated with Esketamine constitutes 95.8 % of the income generated from caring for these patients. This not only raises questions about the pricing of this drug but also highlights the lack of a funding system for costly psychiatric drugs. This concern extends to somatic treatments associated with psychiatric care.

Healthcare Costs Associated with Potentially Inappropriate Medication Prescribing Detected by Computer Algorithm Among Older Patients.

INTRODUCTION: Potentially inappropriate medication prescribing (PIP) among older patients is associated with an increased risk of adverse events and hospitalization, and sometimes increased healthcare costs. OBJECTIVE: The aim of this study was to explore the association between healthcare costs and PIP exposure among older patients. METHODS: Analyses were conducted using data from the Multidomain Alzheimer Preventive Trial (MAPT). A computer algorithm was constructed to detect PIP based on various different explicit criteria-based tools, and the results were expressed in number of medication-related potential non-compliances (MRNCs). A prescription was considered potentially inappropriate if there were one or more MRNCs. We performed a cost analysis from the French National Health Insurance perspective, and also performed a multivariate analysis to identify the association between healthcare costs and PIP (number of MRNCs). RESULTS: The computer algorithm analyzed medication prescribing from included patients (N = 1525 aged 75.3 ± 4.4 years; 64% women [n = 978]). PIP was associated with increased total healthcare costs and non-medication healthcare costs after adjusting for potential confounders. We also noted that healthcare costs tended to increase with the number of MRNCs. The mean additional healthcare costs were €517, €921, and €1669 per patient and year for patients with one or two MRNCs, three or four MRNCs, and five or more MRNCs, respectively, in comparison with patients with appropriate medication prescriptions. CONCLUSION: These observations led us to conclude that interventions focused on reducing PIP could result in savings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00672685.

Screening for deficits on intrinsic capacity domains and associated healthcare costs.

BACKGROUND/OBJECTIVE: Intrinsic capacity (IC) defined by the World Health Organization is divided into six domains (locomotion, psychological, vitality/nutrition, cognition, vision and hearing). The main objective of this study therefore is to explore the association between healthcare costs and IC domains deficits among older patients. PARTICIPANTS AND SETTING: This longitudinal secondary analysis was performed on data from the Multidomain Alzheimer Preventive Trial (MAPT), a 3-year randomized controlled trial with non-demented community-dwelling participants aged 70 years or over. METHODS: We used an adapted version of the ICOPE (Integrated Care for Older People) Step 1 to screen for the six operational IC domains deficits at three time-points: baseline, one year and two years. We performed bivariate and multivariate analyzes using generalized linear models and generalized estimating equation models to identify associations between healthcare cost and deficits on IC domains. RESULTS: We analyzed 693 patients (aged 75.2 ± 4.22 years; 64% women (N = 442)). At baseline, among the included patients, 89% had at least one impairment in IC domains (N = 619). A deficit on visual capacity was associated with increased immediate healthcare costs (CR: 1.48; 95CI: [1.16-1.89]). Regarding persistent impairment of IC, locomotor (CR: 1.27; 95CI: [1.01-1.60], additional annual healthcare cost: €1092 per patient) and psychological (CR: 1.28; 95CI: [1.03-1.59], additional annual healthcare cost: €817 per patient) capacities were associated with increased healthcare costs. CONCLUSION: In conclusion, this study showed that some deficits on IC domains, as measured by simple screening tests and questions, can be associated with higher healthcare costs. CLINICALTRIALS: gov identifier: NCT00672685.

Potentially Inappropriate Medication Prescribing Detected by Computer Algorithm among Older Patients: Results from the MAPT Study.

(1) Background: Some medications may be dangerous for older patients. Potentially inappropriate medication prescribing (PIP) among older patients represents a significant cause of morbidity. The aim of this study was to create an algorithm to detect PIP in a geriatric database (Multidomain Alzheimer Preventive Trial (MAPT) study), and then to assess the algorithm construct validity by comparing the prevalence of PIP and associated factors with literature data. (2) Methods: An algorithm was constructed to detect PIP and was based on different explicit criteria among which the European list of potentially inappropriate medications (EU(7)-PIM), the STOPP and START version 2 tools. For construct validity assessment, logistic mixed-effects model repeated measures analyses were used to identify factors associated with PIP. (3) Results: Prevalence of PIP was 59.0% with the EU(7)-PIM list criteria, 43.2% with the STOPP criteria and 51.3% with the START criteria. Age, polypharmacy, and higher Charlson comorbidity index were associated with PIP. (4) Conclusions: Prevalence of PIP and associated factors are consistent with literature data, supporting the construct validity of our algorithm. This algorithm opens up interesting perspectives both in terms of analysis of very large databases and integration into e-prescribing or pharmaceutical validation software.

[Analysis of regulatory status changes of drugs in France: 2010-2019]. / Analyse des modifications de statut réglementaire des médicaments en France : 2010­2019.

OBJECTIVES: The existence of borderline products between the status of a medicinal product and other less regulated products allows some products to have different statuses or even to change from one status to another. In order to quantify these changes, a review of medicines that have changed from drug status to other statuses (medical device, cosmetic product or food supplement) in France between 2010 and 2019 was performed. METHOD: The lists of medicinal products with archived or revoked marketing authorization (MA) from the French National Authority's Register of Medicinal Products were analyzed in order to identify the medicinal products withdrawn from the market between January 1, 2010 and September 30, 2019 that could be considered as products with a "potential for status change". Then, we searched on the official websites of the MA holders and other firms, for a possible return to the market with a different status, marketed by the same firm (self-change of status) or a different firm (hetero-change of status). RESULTS: Out of a list of 206 drugs identified as "with potential for status change", we detected a total of 101 status changes, including 36 auto-changes and 65 hetero-changes. These changes mainly concern vitamin or herbal drugs later marketed as food supplements (30 cases of auto-changes and 60 cases of hetero-changes). There are also 6 cases of switching to cosmetic product and 5 cases of switching to medical device. CONCLUSION: The existence of no clear distinction between the different statuses of health products facilitates their status changes. The increasing shift from "medicines" to less regulated products, the trivialization of their use by the public and their increasing consumption make them a fundamental issue of social pharmacology, requiring to raise the awareness of consumers and health professionals.

Impact of a Pharmacist-included Mobile Geriatrics team intervention on potentially inappropriate drug prescribing: protocol for a prospective feasibility study (PharMoG study).

INTRODUCTION: Research has shown that potentially inappropriate drug prescription (PIDP) is highly prevalent in older people. The presence of PIDPs is associated with adverse health outcomes. This study aims to evaluate the impact of a PHARmacist-included MObile Geriatrics (PharMoG) team intervention on PIDPs in older patients hospitalised in the medical, surgical and emergency departments of a university hospital. METHODS AND ANALYSIS: The PharMoG study is a prospective, interventional, single-centre feasibility study describing the impact of a PharMoG team on PIDPs in older hospitalised patients. Pharmacist intervention will be a treatment optimisation (clinical medication review) based on a combination of explicit and implicit criteria to detect PIDPs. The primary outcome is the acceptance rate of the mobile team's proposed treatment optimisations related to PIDPs, measured at the patient's discharge from the department. This pharmacist will work in cooperation with the physician of the mobile geriatric team. After the intervention of the mobile geriatric team, the proposals for improving therapy will be sent to the hospital medical team caring for the patient and to the patient's attending physician. The patient will be followed for 3 months after discharge from the hospital. ETHICS AND DISSEMINATION: This study was approved by the South-West and Overseas Territories II Ethics Committee. Oral consent must be obtained prior to participation, either from the patient or from the patient's representative (trusted person and/or a family member). The results will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04151797.

Cost-minimization analysis between intravenous iron sucrose and iron sucrose similar in hemodialysis patients.

OBJECTIVES: Intravenous iron and erythropoiesis-stimulating agents are used to manage anemia in chronic hemodialysis patients. The interchangeability between intravenous iron sucrose preparations is still debated. We evaluated how cost and effectiveness were impacted when chronic hemodialysis patients were switched from an original iron sucrose product to an iron sucrose similar preparation. METHODS: A single center sequential observational retrospective study was conducted at a French hospital. The same patients were followed during two 24-week periods (iron sucrose in period P1; and iron sucrose similar in period P2). Anemia-related treatment costs were assessed in P1 and P2 from a hospital perspective. Sensitivity analyses were performed to assess the robustness of the results. RESULTS: Our study included 109 patients (105 analyzed patients and 4 patients with missing data). The mean hemoglobin level was not different between P1 and P2 (p = 0.92). The mean differential cost per patient was + €13.90 (P2 - P1). The factors with the biggest impact on this result were the prices of epoetin alfa and iron sucrose. CONCLUSION: This cost minimization analysis suggests that for chronic hemodialysis patients, iron sucrose and iron sucrose similar have the same efficacy and that using iron sucrose similar was more expensive in 66.7% of iterations.

Cost analysis of potentially inappropriate medication in older hospitalized patients.

Objectives: Pubmed literature search show that the prescription of potentially inappropriate medications is a major concern in older hospitalized patients, both from a clinical and financial perspective. This study aims to identify factors associated with exposure and potentially inappropriate medication costs in older hospitalized patients and to assess the financial impact of substituting these medications with safer alternatives. Methods: We performed an observational cross-sectional study of all patients aged 75 years or older hospitalized in a university hospital (except geriatric wards) on a given day. Potentially inappropriate medications were identified using European and French guidelines. Results: A total of 365 patients were included. At least one potentially inappropriate medication was prescribed in 50.4% of these patients. This contributed 19.7% [16.1; 23.6] to the average cost of medication per patient. Substitution of these medications with recommended alternatives was cost saving: average incremental cost per patient: -3.97 € [-7.21; -1.58]. Both polypharmacy and type of ward providing care were associated with increased costs of potentially inappropriate medications. Conclusions: This study assessed the prevalence of potentially inappropriate medications in older hospitalized patients and established that their substitution by alternative medications provided a cost saving.

Patient access to orphan drugs in France.

BACKGROUND: Since incentives were introduced to promote orphan drugs in Europe, several dozens of drugs have been registered at the European level. However, patient access on a national level remains very heterogeneous across Europe. This can be explained by healthcare organization and drug reimbursement, which are within the purview of each Member State. We studied access to orphan drugs in France from the patients' point of view, including marketing but also ease of supply from patients' perspective, financial and time-based dimensions. RESULTS: We identified 91 registered orphan drugs in Europe, corresponding to 115 orphan drug-therapeutic indication pairs. In France, 78.3% (90/115) of these pairs were marketed: 100% were available to inpatients and 75.6% were available to outpatients. The median period between granting of the European marketing authorization and publication of the reimbursement decision was 360 days. The broadest availability-through community pharmacies-was guaranteed in only 31.1% of cases. Prescriptions were mainly restricted either to hospital-based doctors or to specialists. Inpatients were not financially responsible for these prescriptions and 72% of the orphan drug-therapeutic indication pairs available to outpatients were fully covered by national health insurance in France. CONCLUSIONS: Patient access to orphan drugs is not universal in France. Access to reimbursement has a strong impact on patients' effective access to orphan drugs, which may be restricted by difficulties with assessing the clinical value of these drugs and with pricing issues. Prescribing restrictions and drug delivery systems influence the ease of patients' supply for reimbursed orphan drugs for patients. Patients do not seem to be limited by financial issues, but the growing budgetary impact of orphan drugs is worrisome from a societal point of view.

[Chapter 5. Biosimilars: a regulatory framework at the crossroads of health security and health economics]. / Chapitre 5. L'encadrement des médicaments biosimilaires à la croisée des logiques sanitaires et économiques.

Expiration of patents for biologic drugs allows marketing of biosimilars as copies of reference biologic drugs. The major benefit of biosimilars for health systems relies on the fact that they are likely to bring progress in terms of efficiency and accessibility. Their legal framework is mixed: European for quality, efficiency and safety; national for socio-economic characteristics. At the European level, our analysis highlights a legal and political corpus generally favorable to the development of biosimilars, despite both organizational and structural limits. In France, decisions related to refund, prices and use of biosimilars reveal hesitations between health and economic issues. Ten years after the of the first biosimilars were licensed, national and European policies result in uncertainty for each stakeholder, respectively on profitability for industrials, efficiency for payers, and risk/benefit ratio for users (healthcare professionals and patients).

Cost Effectiveness of Candida Polymerase Chain Reaction Detection and Empirical Antifungal Treatment among Patients with Suspected Fungal Peritonitis in the Intensive Care Unit.

BACKGROUND: Mortality from intra-abdominal candidiasis in intensive care units (ICUs) is high. It takes many days for peritoneal-fluid fungal culture to become positive, and the recommended empirical antifungal therapy involves excessive costs. Polymerase chain reaction (PCR) should produce results more rapidly than fungal culture. OBJECTIVES: To perform a cost-effectiveness analysis of the combination of several diagnostic and therapeutic strategies to manage Candida peritonitis in non-neutropenic adult patients in ICUs. METHODS: We constructed a decision tree model to evaluate the cost effectiveness. Cost and effectiveness were taken into account in a 1-year time horizon and from the French National Health Insurance perspective. Six strategies were compared: fluconazole or echinocandin as an empirical therapy, plus diagnosis by fungal culture or detection by PCR of all Candida species, or use of PCR to detect most fluconazole-resistant Candida species (i.e., Candida krusei and Candida glabrata). RESULTS: The use of fluconazole empirical treatment and PCR to detect all Candida species is more cost effective than using fluconazole empirical treatment without PCR (incremental cost-effectiveness ratio of €40,055/quality-adjusted life-year). Empirical treatment with echinocandin plus PCR to detect C. krusei and C. glabrata is the most effective strategy, but has an incremental cost-effectiveness ratio of €93,776/quality-adjusted life-year. If the cost of echinocandin decreases, then strategies involving PCR plus empirical echinocandin become more cost-effective. CONCLUSIONS: Detection by PCR of all Candida species and of most fluconazole-resistant Candida species could improve the cost-effectiveness of fluconazole and echinocandin given to non-neutropenic patients with suspected peritoneal candidiasis in ICUs.

Drug selection in French university hospitals: analysis of formularies for nine competitive pharmacological classes.

AIM: To give a panorama of the selectivity and agreement of French university hospitals' drug formularies (HDF) for nine competitive classes. METHODS: All university hospitals were asked to send their HDF and selection criteria as of January 2009 for nine competitive pharmacological classes (proton pump inhibitors, serotonin antagonists, low molecular weight heparins, erythropoietins, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, statins, α-adrenoreceptor antagonists and selective serotonin re-uptake inhibitors). Selectivity of HDF was estimated by the percentage of drug entities selected by the hospital within the pharmacological class. Agreement between hospitals was assessed with modified kappa coefficients for multi-raters. RESULTS: Twenty-one out of the 29 hospitals agreed to participate. These hospitals selected between 34% and 63% of the drug entities available for the nine classes, which represented 18 to 35 agents. Regarding the nature of chosen drug entities, the overall level of agreement was 'fair' and varied with pharmacological classes. Selection criteria were sent by only 12 hospitals. The technical component was the most important element in all hospitals. The weight of the economic component varied between 20% and 40% in the tender's grade. DISCUSSION: Large variations were seen in the number and nature of drugs selected by university hospitals which can be attributable to two successive decision-making processes (evaluation by the Drug and Therapeutics Committee followed by the purchasing process).

Impact of etanercept on the costs of rheumatoid arthritis (RA): results from a French observational study.

INTRODUCTION: Economical impact of rheumatoid arthritis (RA) has been widely modified thanks to TNF inhibitors. Our study aims to estimate the impact etanercept prescription, in term of health resources consumption, within a regional cohort of French RA patients. METHODS: The study included 148 RA patients, with a mean follow-up duration of 343 days before and after etanercept initiation. Data were anonymously collected from ERASME database of French Health Insurance in Midi-Pyrénées region. A patient-by-patient microcosting approach was performed. RESULTS: The average annual cost per patient, attributable to RA, was 2.8 times higher after treatment by etanercept than before (15,148.57euro versus 5248.95euro). We observed a rise in pharmaceutical costs, from 11.7% of direct medical costs before to 69.7% after etanercept initiation (120.12euro versus 9995.23euro). We observed a small decrease particularly for NSAIDs (142.14euro versus 102.21euro) and physiotherapy (286.40euro versus 138.77euro). Attributable act costs and indirect costs did not differ before and after etanercept initiation. DISCUSSION: In this short-term study, initiation of etanercept in RA patients did not come along with a decrease of consumption of health resources. Long-term studies are needed to reveal a potential economical advantage as a consequence of the clinical, structural and functional efficacy of anti-TNF.

[Cost of rheumatoid arthritis in france: comparison leflunomide/etanercept]. / Coût de la polyarthrite rhumatoïde en France: comparaison léflunomide/étanercept.

Treatment of rheumatoid arthritis was deeply modified with the availability since 1999 of anti-TNFalpha. The clinical superiority of these drugs compared to traditional treatments is proven, but can one make the assumption that the cost of these innovative treatments is partially compensated by a reduction of consumption of other health resources? A retrospective observational study was carried out in the Midi-Pyrenees area, from the point of view of health insurance, to compare the consumed health resources between two cohorts of patients, one treated by etanercept (Enbrel) and the other by leflunomide (Arava). Two hundred and fifty three patients were included in the etanercept cohort and 539 in the leflunomide cohort. The average annual PR cost for a patient treated with etanercept is 13 936 euro and 5 764 euro for a patient treated with leflunomide. The health costs avoided by recourse to etanercept do not compensate the high cost of this drug.

[Methods for the measurement of drug consumption: application to antibiotics]. / Méthodes de mesure de la consommation médicamenteuse: application aux antibiotiques.

OBJECTIVE: The aim of this article is to present and compare the different methods used to study drug consumption. METHODS: Particular attention is given to one method, the defined daily dose (DDD), for antibiotic dispensation data in Toulouse University Hospital Centre between 2001 and 2003. RESULTS: Data, expressed in units of packaging, were converted into grams of active substance and then to number of DDD. The number of hospitalization days was used to calculate the penetration index (ratio of number of DDD to the number of hospitalization days). Penetration indexes were similar for each year of study period: 60.6 for 100 patient-days in 2001, 67.7 in 2002 and 66.6 in 2003 (p = 0.37). The most prescribed class was penicillin, most often amoxicillin. CONCLUSION: Use of DDD methodology and penetration index is an accessible and simple tool for monitoring consumption of antibiotics as well as other drugs.