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.

[SARS-COV-2 pandemic: Involvement of the hospital pharmacist in securing patient care]. / Pandémie à SARS-COV-2 : implication du pharmacien hospitalier dans la sécurisation de la prise en charge des patients.

OBJECTIVES: In the context of the SARS-CoV-2 pandemic, hospital pharmacists supported the implementation of recommendations and ensured the safety of patient medication management. The aim of this study is to establish the interest of the involvement of the hospital pharmacist in this context by describing and comparing the activities carried out with patients with COVID-19 and those without. METHODS: During the study period, data on clinical pharmacy activities with hospitalized patients were collected and analyzed: pharmaceutical analysis of prescriptions, participation in multi-professional consultation meetings (RCP) dedicated to COVID-19, and monitoring of adverse events. RESULTS: The activities concerned 1483 patients, including 444 with COVID-19, resulting in 575 pharmaceutical interventions (PI). The main problems identified were overdoses, untreated indications, and drug-drug interactions (DDI). AMIs were significantly more common in patients with COVID-19, with 73.3% involving disease-specific therapies. Eleven PIs had a life-threatening impact, 189 a major impact. During the PCRs, 36 PIs were performed for 59% of the patients presented. A pharmacovigilance report was performed for a quarter of patients treated with hydroxychloroquine and 33% of patients treated with lopinavir/ritonavir. CONCLUSIONS: This study demonstrates the value of involving hospital pharmacists in the drug management of patients with COVID-19, particularly with the evolution of available therapies and the implementation of vaccination, in order to reduce the spread of SARS-COV2 and limit the appearance of resistance.

Comparing different robots available in the European market for the preparation of injectable chemotherapy and recommendations to users.

INTRODUCTION: Recent advances in technology have made it possible to develop robots for preparing injectable anticancer drugs. This study aims to compare characteristics between robots available in the European market in 2022 and to help future pharmacy users in their choices. METHODS: Three sources of data were used: (1) a review of published articles in the MEDLINE database from November 2017 to end of June 2021 on chemotherapy-compounding robots used in hospital; (2) all manufacturers' documentation, and (3) demonstrations of robot operations in real hospital conditions and discussions with users and manufacturers. Robot characteristics included number of robots installed, general technical characteristics, type of injectable chemotherapy produced and compatible materials, productivity data, preparation control methods, residual manual tasks, chemical and microbiological risk management, cleaning method, software, and implementation time. RESULTS: Seven robots commercialized were studied. Several technical characteristics have to be taken into account in selecting the robot whose match the specific needs of a particular hospital, and which often require rethinking the current production workflow as well as the organization of the pharmacy unit. In addition to increasing productivity, the robots improve the quality of production thanks to better traceability, reproducibility, and precision of sampling. They also improve user protection against chemical risk, musculoskeletal disorders, and needle wounds. Nevertheless, when robotization is being planned, there are still numerous residual manual tasks to keep in mind. CONCLUSION: Robotization of the production of injectable anticancer drugs is booming within anticancer chemotherapy preparation pharmacy units. Feedback from this experience needs to be further shared with the pharmacy community regarding this significant investment.

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.

Intravenous route for folate supplementation in a patient with celiac disease treated by pemetrexed-based chemotherapy for non-small-cell lung cancer.

INTRODUCTION: Oral folic acid supplementation is essential for patients treated with pemetrexed, to prevent the risk of severe hematologic toxicity. In case of intestinal absorption disorder, no recommendations exist for intravenous folic acid supplementation. CASE REPORT: We describe a 74-year-old patient with multimetastatic non-small-cell lung adenocarcinoma, receiving first-line chemotherapy with carboplatin AUC5, pemetrexed 500 mg/m2 and pembrolizumab 200 mg intravenously every 3 weeks. The patient presented neglected celiac disease, resulting in malabsorption syndrome with iron and folic acid deficiency. The question was how to administer folic acid supplementation during the pemetrexed-based chemotherapy. MANAGEMENT AND OUTCOMES: Intravenous injection of 200 mg levoleucovorin on day 1 of cycle 1 of pemetrexed-based chemotherapy was administered and well tolerated. During the second cycle, the levoleucovorin perfusion was not renewed by omission. The patient was hospitalized for 7 days because of febrile aplasia. Piperacillin-tazobactam was started, and then switched to amoxicillin-clavulanate plus ciprofloxacin. After this episode of post-chemotherapy febrile aplasia, it was decided to systematically supplement the patient with intravenous levoleucovorin, with blood folate concentration monitoring at each cycle. At 16 months after start of treatment, the patient was in complete remission, indicating that the immune-chemotherapy was effective, with no further febrile neutropenia. DISCUSSION/CONCLUSION: This case report highlights intravenous levoleucovorin supplementation as an alternative to oral folic acid if needed during pemetrexed-antifolate-based chemotherapy.

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.

Preparations of exploration of immediate hypersensitivity to antineoplastic agents: An oncology pharmacy perspective.

BACKGROUND: Cancer patients are being exposed to antineoplastic drugs more frequently and for longer periods, resulting in a higher risk of hypersensitivity reactions. The aim of this study was to assess the pharmaceutical time and direct cost of drug allergy explorations following immediate hypersensitivity reactions to antineoplastic agents. METHODS: A micro-costing method was used to collect data on consumption of human and material resources for allergy exploration preparations. The monetisation was carried out on the basis of prices and hourly wage costs applied in 2018. The number and type of allergy explorations prepared by the pharmacy as well as nature of antineoplastic drugs tested, and the number of culprit drugs reintroductions were collected. RESULTS: Almost 1.5 h is required to realise allergy tests for one patient including pharmacist time for prescription analysis and pharmacy technician's time for tests preparation. The mean manufacturing cost of these tests is estimated at €62.87 (€57.82-65.49) per culprit drug for one patient. Programming patients according to culprit drugs tested allows rationalising healthcare provider time and increasing efficiency. From January 2010 to December 2018, 277 patients were tested and 490 allergy explorations were performed, corresponding to more than 5000 preparations. Mostly, the culprit drug could be reintroduced (n = 383, 78.2%) allowing patients to receive the best possible treatment. CONCLUSION: Management of hypersensitivity reactions is constantly progressing, as it contributes to improving patient care in oncology. This activity is time-consuming for the pharmacy team but allows patients with previous hypersensitivity reaction to continue effective treatment.

Immunosuppression medication adherence after allogeneic hematopoietic stem cell transplant: Impact of a specialized clinical pharmacy program.

This study aims to evaluate the impact of implementing a specialized clinical pharmacy program in patients with allogeneic hematopoietic stem cell transplant (HSCT) on their adherence to the immunosuppression treatment after discharge. A prospective open interventional design using a retrospective control group was used. The intervention was based on pharmaceutical consultations: the first was performed the day before discharge of HSCT unit and the next consultations during day-care follow-up (weeks 2 and 4 after discharge). Proactive medication reconciliation was implemented with a complete list of medications before the discharge prescription. The discharge prescription summarized on a personalized drug schedule was explained to the patient. The importance of optimal adherence and the potential problems related to self-medication were explained to the patient. Immunosuppression drug adherence was assessed by a direct method using serum levels of calcineurin inhibitors. The potential impact on acute GvHD, and infection was investigated. Twenty-six patients were included in the specialized clinical pharmacy program and 35 patients were in the control group. Seventy-nine pharmaceutical consultations were conducted in the intervention group, lasting a mean 25 min and 16 min for the first and following consultations, respectively. Serum levels in the therapeutic target range were higher in the intervention group (61.5% versus 53.0%, p = 0.07), with greater intra-individual variation (p = 0.005). There was no significant intergroup difference in acute GvHD (53.8% versus 50.3%, p = 0.85) or infection (26.9 versus 22.8%, p = 0.72). The implementation of a specialized clinical pharmacy program for patients who have received allogeneic HSCT seems to be beneficial for immunosuppression drug adherence; this now needs to be confirmed in a multicenter study involving a larger number of patients.

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.

Immunomodulatory drugs in multiple myeloma: Impact of the SCARMET (Self CARe and MEdication Toxicity) educational intervention on outpatients' knowledge to manage adverse effects.

Long-term multiple myeloma therapy by immunomodulatory drugs (IMiDs) raises the question of management of adverse effects. The aim of this study is to assess the impact of an educational session for patients on the acquisition of knowledge to manage hematologic and thromboembolic adverse effects of IMiDs. In this prospective single-center study, patients attended an educational session with a hospital clinical pharmacist and a nurse. The primary endpoint was the patient's level of knowledge for the management of IMiDs adverse effects, assess with a dedicated questionnaire administered before the session then 1 and 6 months after. Assessment of knowledge was combined with self-assessment of certainty. The secondary endpoints were adherence and IMiD treatment satisfaction. 50 patients were included. Patient knowledge increased at 1 month (p<0.001) despite a loss of knowledge at 6 months (p<0.05). Six months after the educational intervention, the number of patients with skills considered satisfactory by the pharmacist and nurse increased (p<0.01). Most patients showed satisfactory adherence, with medication possession ratio ≥ 80%. The Self CARe and MEdication Toxicity (SCARMET) study highlighted the impact of multidisciplinary follow-up in multiple myeloma patients to improve knowledge of toxicity self-management.

Cancer, immune suppression and Coronavirus Disease-19 (COVID-19): Need to manage drug safety (French Society for Oncology Pharmacy [SFPO] guidelines).

The Coronavirus disease (COVID-19) pandemic is disrupting our health environment. As expected, studies highlighted the great susceptibility of cancer patients to COVID-19 and more severe complications, leading oncologists to deeply rethink patient cancer care. This review is dedicated to the optimization of care pathways and therapeutics in cancer patients during the pandemic and aims to discuss successive issues. First we focused on the international guidelines proposing adjustments and alternative options to cancer care in order to limit hospital admission and cytopenic treatment in cancer patients, most of whom are immunocompromised. In addition cancer patients are prone to polypharmacy, enhancing the risk of drug-related problems as adverse events and drug-drug interactions. Due to increased risk in case of COVID-19, we reported a comprehensive review of all the drug-related problems between COVID-19 and antineoplastics. Moreover, in the absence of approved drug against COVID-19, infected patients may be included in clinical trials evaluating new drugs with a lack of knowledge, particularly in cancer patients. Focusing on the several experimental drugs currently being evaluated, we set up an original data board helping oncologists and pharmacists to identify promptly drug-related problems between antineoplastics and experimental drugs. Finally additional and concrete recommendations are provided, supporting oncologists and pharmacists in their efforts to manage cancer patients and to optimize their treatments in this new era related to COVID-19.

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.

Delayed methotrexate elimination: Incidence, interaction with antacid drugs, and clinical consequences?

The aim of this retrospective cohort study was to investigate the incidence of delayed methotrexate elimination in patients treated with high-dose methotrexate (≥1 g/m2 ) for haematological malignancy and to identify the impact of interacting drugs, especially proton-pump inhibitors (PPIs) and ranitidine. All patients treated with high-dose methotrexate over a 6 year period in the haematology department of the Lyon Sud University Hospital (Hospices Civils de Lyon, France) were included. Potential risk factors for delayed methotrexate elimination were tested in a generalized linear model by univariate analysis: patient age, gender, methotrexate dose, administration of PPI or ranitidine, and concomitant nephrotoxic drugs. A total of 412 cycles of methotrexate were administered to 179 patients. Proton-pump inhibitors were co-administered with methotrexate in 127 cycles and ranitidine in 192 cycles. Ninety-three cycles included no antacid drugs. A total of 918 plasma methotrexate assays were performed. Methotrexate concentrations were checked at 24 hours in 92% of cycles. Delayed methotrexate elimination was observed in 20.9% of cycles. A total of 63 cycles with delayed methotrexate elimination were only identified on plasma methotrexate measures at 72 hours: ie, plasma methotrexate was in the normal range at 24 and 48 hour post injection. Use of PPI/ranitidine or no antacid drugs did not increase risk of delayed elimination, with respectively delayed methotrexate elimination in 20.5%, 21.9%, and 19.4% of cycles (P = .89). Impaired baseline creatinine clearance showed significant association in univariate analysis. Fifteen patients showed grade 1 acute kidney injury, 1 grade 2, 2 grade 3, and none grade 4. For half of these cases, delayed methotrexate elimination was observed and the 2 grade 3 events appeared in patients treated with PPIs. This retrospective study suggests that there is no association between concomitant use of proton-pump inhibitors (pantoprazole and esomeprazole) or ranitidine and delayed methotrexate elimination.

[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.