Cost-effectiveness of the ONCORAL multidisciplinary programme for the management of outpatients taking oral anticancer agents at risk of drug-related event: protocol for a pragmatic randomised controlled study.

INTRODUCTION: The development of oral anticancer agents (OAA) has profoundly changed cancer care, leading patients to manage their chemotherapy treatment on an outpatient basis. The prevention of iatrogenic effects of OAA remains a major concern, especially since their side effects are not less serious than those of intravenous chemotherapy. The ONCORAL programme was set up to secure the management of OAA in cancer patients followed at the Lyon University Hospital. This multidisciplinary programme involves hospital pharmacists, nurses, oncologists, and haematologists, as well as community health professionals. Given the economic stakes that this programme entails for the health system, a medico-economic study was designed. METHODS AND ANALYSIS: This is a prospective controlled study, with individual open-label randomisation. A total of 216 outpatients treated with OAA and at risk of developing a drug-related iatrogenic event, will be randomised (2:1) to undergo follow-up in the ONCORAL programme or usual care. The primary outcome will be the estimation of the incremental cost-effectiveness ratio (difference in total costs per quality adjusted life years gained) at 12 months between the two groups. The secondary outcomes will be evaluation of OAA management consequences (relative-dose intensity, adherence, adverse drug events, drug-drug interactions, and proven medication errors), evaluation of overall survival and cancer-related quality of life, and patient-reported outcomes in relation to the treatment. A budget impact analysis will be implemented. Patient and health professional satisfaction regarding the ONCORAL programme will be measured. ETHICS AND DISSEMINATION: Approval to conduct this study was obtained from an Ethics Committee (Comité de Protection des Personnes Ile-de-France VI) in October 2019, and from the French data protection agency (Commission Nationale de l'Informatique et des Libertés), according to the French Law. Trial results will be disseminated at clinical conferences and published in peer-reviewed journals. TRIAL REGISTRATION: NCT03660670.

Clinical impact and cost-saving analysis of a comprehensive pharmaceutical care intervention in older patients with cancer.

BACKGROUND: Hospital admission and discharge are at high risk of drug-related problems (DRPs) in older patients with cancer. This study aimed to assess the clinical and economic impact of a comprehensive pharmaceutical care intervention (RECAP) to optimize drug therapy in patients with cancer ≥75 years admitted to oncology or geriatric wards. METHOD: RECAP intervention was defined as follows: at admission and discharge, hospital pharmacists conducted comprehensive medication reconciliation and review, identified relevant DRPs and provided optimization recommendations to prescribers; at discharge, pharmacists also provided patient education and shared information with primary care providers. The impact of the intervention was assessed by the rate of implementation of recommendations by the prescribers and the evolution of polypharmacy rate; a peer review of the clinical significance of DRPs was performed by an expert panel of geriatric oncologists and pharmacists. A cost saving analysis compared cost avoided through resolution of DRPs to cost of pharmacist's time. RESULTS: From January 2019 and August 2020, 201 patients were included (median age 80 [75-97] years), 68.7% with solid tumors. DRPs requiring optimization were identified in 70.9% of patients at admission (mean 1.7 DRP/patient) and 47.7% at discharge (0.9 DRP/patient). Most pharmacist recommendations (70.8%) were followed by prescribers, allowing the correction of 1.2 DRP/patient at admission and 0.7 DRP/patient at discharge. Half of resolved DRPs were rated as clinically significant. However, polypharmacy rate was not reduced at discharge. Cost comparison showed $7.2 avoided for $1 invested, with an estimated total net benefit of $354,822 (mean $1766 per patient). CONCLUSIONS: The RECAP model significantly reduces DRPs in hospitalized older patients with cancer. The model was cost saving, confirming the value of implementing it in routine practice.

Development of Indirect Health Data Linkage on Health Product Use and Care Trajectories in France: Systematic Review.

BACKGROUND: European national disparities in the integration of data linkage (ie, being able to match patient data between databases) into routine public health activities were recently highlighted. In France, the claims database covers almost the whole population from birth to death, offering a great research potential for data linkage. As the use of a common unique identifier to directly link personal data is often limited, linkage with a set of indirect key identifiers has been developed, which is associated with the linkage quality challenge to minimize errors in linked data. OBJECTIVE: The aim of this systematic review is to analyze the type and quality of research publications on indirect data linkage on health product use and care trajectories in France. METHODS: A comprehensive search for all papers published in PubMed/Medline and Embase databases up to December 31, 2022, involving linked French database focusing on health products use or care trajectories was realized. Only studies based on the use of indirect identifiers were included (ie, without a unique personal identifier available to easily link the databases). A descriptive analysis of data linkage with quality indicators and adherence to the Bohensky framework for evaluating data linkage studies was also realized. RESULTS: In total, 16 papers were selected. Data linkage was performed at the national level in 7 (43.8%) cases or at the local level in 9 (56.2%) studies. The number of patients included in the different databases and resulting from data linkage varied greatly, respectively, from 713 to 75,000 patients and from 210 to 31,000 linked patients. The diseases studied were mainly chronic diseases and infections. The objectives of the data linkage were multiple: to estimate the risk of adverse drug reactions (ADRs; n=6, 37.5%), to reconstruct the patient's care trajectory (n=5, 31.3%), to describe therapeutic uses (n=2, 12.5%), to evaluate the benefits of treatments (n=2, 12.5%), and to evaluate treatment adherence (n=1, 6.3%). Registries are the most frequently linked databases with French claims data. No studies have looked at linking with a hospital data warehouse, a clinical trial database, or patient self-reported databases. The linkage approach was deterministic in 7 (43.8%) studies, probabilistic in 4 (25.0%) studies, and not specified in 5 (31.3%) studies. The linkage rate was mainly from 80% to 90% (reported in 11/15, 73.3%, studies). Adherence to the Bohensky framework for evaluating data linkage studies showed that the description of the source databases for the linkage was always performed but that the completion rate and accuracy of the variables to be linked were not systematically described. CONCLUSIONS: This review highlights the growing interest in health data linkage in France. Nevertheless, regulatory, technical, and human constraints remain major obstacles to their deployment. The volume, variety, and validity of the data represent a real challenge, and advanced expertise and skills in statistical analysis and artificial intelligence are required to treat these big data.

Clinical and economic impact of clinical oncology pharmacy in cancer patients receiving injectable anticancer treatments: a systematic review.

PURPOSE: Clinical pharmacy can reduce drug-related iatrogenesis by improving the management of adverse effects of drugs, limiting drug-drug interactions, and improving patient adherence. Given the vulnerability of cancer patients and the toxicity of injectable anticancer drugs, clinical pharmacy service (CPS) could provide a significant clinical benefit in cancer care. This review aims to synthesize existing evidence on clinical pharmacy's impact on patients treated with intravenous anticancer drugs. METHODS: A comprehensive search was performed in the PubMed/Medline database from January 2000 to December 2021, associating the keywords: clinical pharmacy, pharmaceutical care, pharmacist, oncology, and chemotherapy. To be eligible for inclusion, studies have to report clinical pharmaceutical services for patients treated with intravenous chemotherapy with a clinical and/or economic impact. RESULTS: Forty-one studies met the selection criteria. Various CPS were reported: medication reconciliation, medication review, and pharmaceutical interview with patient. There was a lack of randomized study (n = 3; 7.3%). In one randomized controlled trial, pharmaceutical intervention significantly improved quality of life of patients receiving pharmaceutical care during injectable anticancer drugs courses. Economical results appear to show positive impact of clinical pharmacy with cost savings reported from 3112.87$ to 249 844€. Although most studies were non-comparative, they highlighted that clinical pharmacy tend to limit chemotherapy side effects and drug-related problems, improve quality of life and satisfaction of patients and healthcare professional, and a positive economic impact. CONCLUSION: Clinical pharmacy can reduce adverse drug events in cancer patients. More robust and economic evaluations are still required to support its development in everyday practice.

Impact of pharmaceutical care interventions on multidisciplinary care of older patients with cancer: A systematic review.

INTRODUCTION: Optimizing medication use is a major issue in older patients with cancer and pharmacists are increasingly involved in their multidisciplinary care. The implementation of pharmaceutical care interventions must be supported by impact evaluations to enable their development and funding. This systematic review aims to synthesize evidence on the impact of pharmaceutical care interventions in older patients with cancer. MATERIALS AND METHODS: A comprehensive search was performed in the PubMed/Medline, Embase, and Web of Science databases, for articles reporting evaluations of pharmaceutical care interventions for patients with cancer aged 65 years or older. RESULTS: Eleven studies met the selection criteria. Most pharmacists were part of multidisciplinary geriatric oncology teams. Whether in outpatient or inpatient settings, interventions had common components, including patient interview, medication reconciliation, and comprehensive medication review to assess drug-related problems (DRPs). DRPs were identified in 95% of patients with 1.7 to 3 DRPs on average. Pharmacist recommendations resulted in a 20-40% reduction in the total number of DRPs and a 20-25% decrease in the prevalence of DRP. Prevalence of potentially inappropriate or omitted medications and their subsequent deprescribing or addition varied greatly between studies, notably depending on detection tools used. Clinical impact was insufficiently evaluated. Only one study reported a reduction of anticancer treatment toxicities following a joint pharmaceutical and geriatric assessment. A single economic evaluation calculated a potential net benefit of $3,864.23 per patient resulting from the intervention. DISCUSSION: These encouraging results must be confirmed by more robust evaluations to support the involvement of pharmacists in multidisciplinary care of older patients with cancer.

Assessment of Patient Reported Outcomes (PROs) in Outpatients Taking Oral Anticancer Drugs Included in the Real-Life Oncoral Program.

Background In previous studies, patient-reported outcomes (PROs) have been shown to improve survival in cancer patients. The aim of the present study was to assess symptoms potentially related to adverse events experienced by cancer outpatients treated by oral anticancer agents (OAAs) using PROs. Methods Between September 2018 and May 2019, outpatients starting OAAs were included in a 12-week follow-up to assess 15 symptoms listed in the National Cancer Institute PRO Common Terminology Criteria for Adverse Events, using a 5-point scale of severity or frequency. Patients were requested to alert a referral nurse or pharmacist when they self-assessed high-level (level 3 or 4) symptoms. Results 407 questionnaires were completed by 63 patients in which 2333 symptoms were reported. Almost three-quarters (74.6%) reported at least one high-level symptom. The symptoms that were most commonly experienced were fatigue (>9 in 10 patients; 13.2% of symptoms declared), various psychological disorders (>9 in 10 patients; 28.6% of symptoms declared) and general pain (>8 in 10 patients; 9.4% of symptoms declared). Conclusion PROs are appropriate to detect potential adverse events in cancer outpatients treated by OAAs. This study is the first step for integrating the patient's perspective in a digital e-health device in routine oncology care.

Economic impact of clinical pharmaceutical activities in hospital wards: A systematic review.

BACKGROUND: The positive impact of clinical pharmacy services (CPS) in improving clinical outcomes such as reduction of drug related problems is well demonstrated. Despite these results, the deployment of these activities is not systematically observed in the hospital setting. OBJECTIVES: This systematic review first aimed to describe existing evidence regarding economic evaluation of ward-based CPS focusing on the entire treatment of a patient in a hospital setting. Secondly, the quality of economic evaluations of existing evidence was assessed. METHODS: A comprehensive literature search was performed in PubMed/Medline, Science Direct and the NHS Economic Evaluation databases from January 2000 to March 2019. English or French language articles describing an economic evaluation of ward-based CPS on inpatients in hospital settings were included. Articles not describing a single study, dealing with a CPS not considering the entire medication regimen of the patient or presenting both inpatient and outpatient CPS were excluded. Selected articles were analyzed according to Drummond's check-list for assessing economic evaluations. RESULTS: Forty-one studies were included. About one third were American publications. CPS implemented in ICU represented about half of the selected articles. Pharmacist-to-bed ratios varied according to countries and care unit type with the most favorable ratios in ICU and in American studies. Cost-avoidance was mostly used to express economic impact and ranged from €1579 to €3,089 328. Studies yielding the greater economic impact were conducted in the USA with implementation of full-time equivalents pharmacists or establishing of collaborative practice agreements. Only 6 articles dealt correctly with at least 7 of the 10 Drummond's checklist assessment criteria. CONCLUSION: This review suggests that the existing evidence is not sufficient to conclude to a positive economic impact of CPS conducted according to clinical pharmacy guidelines. Funding resources, remuneration of clinical pharmacy activities and provision of standardized national clinical and economic databases appear to be essential evolutions to improve CPS development.

Drug cost savings in phase III hematological oncology clinical trials in a university hospital.

The rapid emergence of expensive anticancer therapies is leading to exponential growth in healthcare expenses. In clinical trials, most investigational drugs are provided free of charge by industrial and academic sponsors. This results in drug cost savings for healthcare payers, who are no longer charged with the cost of the standard-of-care treatment, which would have been administered outside the trial. This study aims to estimate drug cost savings resulting from patient enrolment in hematological oncology clinical trials, from a public payer perspective. Retrospective screening identified all patients with hematological malignancies included from 2011 to 2016 in a phase III trial and having received at least one sponsor-provided cycle. Drug cost savings were defined as the standard treatment costs not charged to the payer due to sponsor provision of treatment. For each patient, cost savings were determined by the number of cycles received in the trial and the cost of standard (control arm) treatment. Of the 345 patients included in eligible trials during study period, 272 received sponsor-provided drugs. Drug cost savings could be estimated for 177 patients (65.1%) included in 27 trials. Total cost savings were €5218 million (US$ 6804 million) for 1720 sponsor-provided cycles. Mean cost saving per patient was €19 182.7 ± 29 865.7 ($25 015.24 ± 39 478.25). Most cost-saving trials were industry-sponsored (77.8%), although academic trials generated 40.15% of total cost savings. Enrolling patients in clinical trials, whether industry-sponsored or academic, leads to substantial drug cost savings for payers. Implications are significant for public payers facing increasing financial constraints, as savings can be reallocated to patient care.

Clinical and economic impact of medication reconciliation in cancer patients: a systematic review.

PURPOSE: Medication reconciliation can reduce drug-related iatrogenesis by facilitating exhaustive information transmission at care transition points. Given the vulnerability of cancer patients to adverse drug events, medication reconciliation could provide a significant clinical benefit in cancer care. This review aims to synthesize existing evidence on medication reconciliation in cancer patients. METHODS: A comprehensive search was performed in the PubMed/Medline, Scopus, and Web of Science databases, associating the keywords "medication reconciliation" and "cancer" or "oncology." RESULTS: Fourteen studies met the selection criteria. Various medication reconciliation practices were reported: performed at admission or discharge, for hospitalized or ambulatory patients treated with oral or parenteral anticancer drugs. In one randomized controlled trial, medication reconciliation decreased clinically significant medication errors by 26%. Although most studies were non-comparative, they highlighted that medication reconciliation led to identification of discrepancies and other drug-related problems in up to 88% and 94.7% of patients, respectively. The impact on post-discharge healthcare utilization remains under-evaluated and mostly inconclusive, despite a trend toward reduction. No comparative economic evaluations were available but one study estimated the benefit:cost ratio of medication reconciliation to be 2.31:1, suggesting its benefits largely outweigh its costs. Several studies also underlined the extended pharmacist time required for the intervention, highlighting the need for further cost analysis. CONCLUSION: Medication reconciliation can reduce adverse drug events in cancer patients. More robust and economic evaluations are still required to support its development in everyday practice.

SMABcare study: subcutaneous monoclonal antibody in cancer care: cost-consequence analysis of subcutaneous rituximab in patients with follicular lymphoma.

Rituximab is used as a standard of care for follicular lymphoma and is usually administered intravenously. A novel subcutaneous formulation recently showed non-inferior efficacy with similar pharmacokinetic and safety profiles compared to intravenous rituximab in patients with follicular lymphoma. This new approach is promising in terms of comfort for patients and time-saving for hospital staff. To evaluate the real-life economic impact of subcutaneous rituximab as maintenance therapy in patients with follicular lymphoma in real life, we conducted a cost-consequence analysis from the hospital's point of view in three French teaching hospitals. Health-related quality of life (EQ-5D-3L) was investigated as well as patients' and nurses' perception. Compared to intravenous rituximab, subcutaneous administration showed an estimated cost-saving of €109.20 per patient per cycle (p < 0.001), 78.6% of which could be attributed to the rituximab cost. Health-related quality of life showed no significant difference between the two groups despite tendencies for greater pain in the subcutaneous group and greater anxiety in the intravenous group. Thus, subcutaneous rituximab had a favorable pharmacoeconomic profile, with clinical efficacy similar to that of intravenous rituximab. The subcutaneous form was preferred by almost all patients, but further consideration should be given to improve the patients' experience: a dedicated day unit with trained medical, nursing, and pharmaceutical staff could be helpful.

[Evolution of reimbursement of high-cost anticancer drugs: Financial impact within a university hospital]. / Évolution du remboursement des anticancéreux inscrits sur la liste en sus : impact financier au sein d'un centre hospitalo-universitaire.

INTRODUCTION: In the context of health expenses control, reimbursement of high-cost medicines with a 'minor' or 'nonexistent' improvement in actual health benefit evaluated by the Haute Autorité de santé is revised by the decree of March 24, 2016 related to the procedure and terms of registration of high-cost pharmaceutical drugs. This study aims to set up the economic impact of this measure. METHOD: A six months retrospective study was conducted within a French university hospital from July 1, 2015 to December 31, 2015. For each injectable high-cost anticancer drug prescribed to a patient with cancer, the therapeutic indication, its status in relation to the marketing authorization and the associated improvement in actual health benefit were examined. The total costs of these treatments, the cost per type of indication and, in the case of marketing authorization indications, the cost per improvement in actual health benefit were evaluated considering that all drugs affected by the decree would be struck off. RESULTS: Over six months, 4416 high-cost injectable anticancer drugs were prescribed for a total cost of 4.2 million euros. The costs of drugs with a minor or nonexistent improvement in actual benefit and which comparator is not onerous amount 557,564 euros. DISCUSSION: The reform of modalities of inscription on the list of onerous drugs represents a significant additional cost for health institutions (1.1 million euros for our hospital) and raises the question of the accessibility to these treatments for cancer patients.

Chemotherapeutic errors in hospitalised cancer patients: attributable damage and extra costs.

BACKGROUND: In spite of increasing efforts to enhance patient safety, medication errors in hospitalised patients are still relatively common, but with potentially severe consequences. This study aimed to assess antineoplastic medication errors in both affected patients and intercepted cases in terms of frequency, severity for patients, and costs. METHODS: A 1-year prospective study was conducted in order to identify the medication errors that occurred during chemotherapy treatment of cancer patients at a French university hospital. The severity and potential consequences of intercepted errors were independently assessed by two physicians. A cost analysis was performed using a simulation of potential hospital stays, with estimations based on the costs of diagnosis-related groups. RESULTS: Among the 6, 607 antineoplastic prescriptions, 341 (5.2%) contained at least one error, corresponding to a total of 449 medication errors. However, most errors (n = 436) were intercepted before medication was administered to the patients. Prescription errors represented 91% of errors, followed by pharmaceutical (8%) and administration errors (1%). According to an independent estimation, 13.4% of avoided errors would have resulted in temporary injury and 2.6% in permanent damage, while 2.6% would have compromised the vital prognosis of the patient, with four to eight deaths thus being avoided. Overall, 13 medication errors reached the patient without causing damage, although two patients required enhanced monitoring. If the intercepted errors had not been discovered, they would have resulted in 216 additional days of hospitalisation and cost an estimated annual total of 92,907€, comprising 69,248€ (74%) in hospital stays and 23,658€ (26%) in additional drugs. CONCLUSION: Our findings point to the very small number of chemotherapy errors that actually reach patients, although problems in the chemotherapy ordering process are frequent, with the potential for being dangerous and costly.

[Direct medical cost of erythropoiesis-stimulating agents in anaemia treatment of chronic renal failure patient: a literature review]. / Coût médical direct des agents stimulant l'érythropoïèse dans le traitement de l'anémie chez le patient insuffisant rénal chronique: revue de la littérature.

INTRODUCTION: Management of anaemia in chronic renal insufficiency (CRI) represents an important medico-economic challenge because of the great number of patients and the cost of the erythropoiesis-stimulating agent (ESA). The aim of this study was to identify determinants of the costs associated with these treatments in order to choose, with equal efficacy, the most efficient ASE. METHOD: A bibliographic research was realised by Medline database interrogation. RESULTS: Among the direct medical costs, five studies showed that acquisition of epoetine alfa (EA) compared to darbepoetin alfa (DA) was less expensive. Concerning the costs associated with the route of administration, the subcutaneous injection (SC) of epoetine allowed a gain in costs because of the decrease of doses compared to the intravenous (IV) route. The switch from EA in SC to DA in IV, for hemodialysis patients, was associated with a reduction of the number of injections and with a treatment's cost lower by DA than by EA. Costs related to the regimen of administration, notably those related to nursing, medical and pharmaceutical time, were negligible towards those associated to the acquisition of the ASE. Finally, the costs of the therapeutic follow-up and treatment of the adverse effects of the ASE were similar between the EA and the DA. CONCLUSION: The costs associated with the prices of acquisition of the ASE, negotiated by the structure of care, represent the most important part of the direct medical costs.