Irvine, Clayton

Introduction Taxane medications, paclitaxel, and docetaxel, are chemotherapy agents that have a higher incidence of reported hypersensitivity and infusion reactions. To help classify these reactions, the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) is utilized. Prophylactic medications have been used to decrease the incidence and severity of these events. At our institution, medications that patients can receive prior to the initiation of a taxane infusion are a histamine 1 receptor antagonist (H1RA), histamine 2 receptor antagonist (H2RA), a steroid or a combination of these medications. The purpose of this retrospective review was to compare the rates and severity of infusion reactions based on the timing of prophylactic medication administration in the first and second doses of taxane infusions. Methods Patients who received paclitaxel or docetaxel from January 30 th , 2022, through January 30 th , 2023, were included in the analysis. To assist in the identification of a reaction, taxane administrations were flagged for review if a rescue medication was administered after the start of a paclitaxel or docetaxel infusion. The rates and severity of infusion reactions were analyzed based on the timing of prophylactic medication administration. A sub-group analysis comparing infusion reaction characteristics between taxanes given, was performed. Results Of the 1486 taxane infusions that were completed within the year, 249 infusion reactions were confirmed and graded utilizing the NCI CTCAE. When examining the first and second doses of a taxane (N = 536), we identified 222 infusions reactions. The odds of a patient having an infusion reaction, during the first and second doses, was found to be less likely for patients given a prophylactic medication 30 min prior to receiving a taxane compared to those who did not receive a pre-medication (p = 0.037). Conclusion This multisite retrospective study showed that administration of prophylactic medications 30 to 80 min prior to the first and second infusion of a taxane was the optimal timing to decrease the likelihood of patients having an infusion reaction. No difference in the severity of the reaction was seen. Most patients were able to complete the entire infusion, regardless of what rescue medications were used following the infusion reaction.

PURPOSE Globally, cancer drug expenditure exceeds $185 in US dollars (USD) billion, with the United States contributing $75 (USD) billion. Many cancer drug doses are calculated on the basis of body weight or body surface area, which often results in leftover drug in partially used single-dose vials (SDVs). The cost of wasted drug is a huge financial burden on the US health care system. We evaluated the cost savings resulting from the reduction of SDV wastage, achieved through the implementation of automated dose rounding rules in electronic health records (EHRs). METHODS Mayo Clinic implemented automated dose rounding rules within the EHR. These rules were designed to round calculated doses to the nearest SDV if the vial size closely matched the original calculated dose, within a 10% threshold. We assessed doses administered between January 2019 and December 2021, and computed cost-savings, waste reduction, and cost of waste for chemotherapy drugs. RESULTS In 3 years, 36.1% of doses were rounded down, 35.8% were rounded up, and 28.1% were exact doses. By rounding doses down to a vial size, we achieved cost-savings of $39.75 (USD) million and prevented 62,065 SDV of cancer drugs from going to waste. By rounding doses up, we avoided wasting $9.95 (USD) million worth of drugs. However, there were still instances where the rounding fell outside of the 10%, resulting in wasted drugs worth $25 (USD) million. CONCLUSION The substantial burden imposed on patients and the US health care system because of cancer drug wastage is of significant concern. Although the automated dose rounding system represents a partial solution for this issue, a comprehensive approach involves the imperative development of policy and legislative solutions to effectively mitigate the challenges associated with cancer drug waste.

Abstract Background Interleukin 6 (IL-6) plays important roles in both innate and adaptive immunity, while dysregulated persistent production of IL-6 is involved in pathological development of various diseases associated with inflammation. Targeting the IL-6 pathway has led to many innovative treatment approaches. Siltuximab and Tocilizumab are monoclonal antibodies targeting IL-6 and IL-6 receptors respectively and have been FDA-approved for treatment of Castleman disease (Siltuximab), a rare lymphoproliferative disorder characterized by hyperproduction of IL-6 with an unknown prevalence, autoimmune diseases such as rheumatoid arthritis (Tocilizumab), and both shown potential as treatment for cytokine release syndrome in hospitalized COVID-19 patients. However, the presence of siltuximab can interfere with IL-6 assays, leading to the use of C-reactive protein (CRP) as a surrogate marker to monitor its efficacy. Aim To evaluate potential Siltuximab and Tocilizumab antibody interference on IL-6 measurements in three different IL-6 protein immunoassays. Method: Serum or EDTA plasma sample pools with different IL-6 concentrations ranging from low (2.3 – 11.1 pg/mL, around the reference interval cut-off for each assay) to high (18.5 – 1142 pg/mL), above reference interval cut-off for each assay) were utilized. Various concentrations of Siltuximab or Tocilizumab were spiked into the sample pools (at 10% of total volume) to achieve final concentrations up to 600 µg/mL and up to 300 µg/mL, respectively. Sample spiked with 10% saline were used as no-drug control. Three assays were used to measure IL-6 concentration: Beckman Access IL-6 assay on UniCel DxI 800 (Beckman Coulter), V-PLEX Plus human IL-6 assay on QuickPlex SQ120 (Meso Scale Diagnostics), and a Luminex cytokine panel assay developed in house (R&D systems) with upper reference interval limits of 6.4,1.8 and 5 pg/mL respectively. Results Siltuximab interfered with the measurement of IL-6 for all three assays. A significant interference (> 20% reduction) was observed at even a very low siltuximab concentrations in all three assays (0.05 µg/mL). In the presence of 5 µg/mL or greater Siltuximab, a maximum reduction of 93%, 83%, and 40% was observed for Beckman Access, R&D Luminex assay, and V-PLEX Plus Mesoscale assay, respectively. Tocilizumab did not interfere with the measurement of IL-6 in the three assays when serum was spiked with up to 300 µg/mL of the drug. Conclusion Siltuximab falsely reduce the measured IL-6 concentration on all three immunoassays tested in this study to differing degrees, whereas Tocilizumab does not. Consider the therapeutic range of Siltuximab (84 to 332 µg/mL) for treatment of Castleman disease, and a half-life of 20.6 days, measurement of IL-6 may not be useful in Siltuximab treated patients for an extended time-period.

Background: Pharmacist order verification is a critical step in ensuring medication safety for patients. While the second pharmacist verification (SPV) before dispensing anticancer therapies has been a longstanding practice, its continued necessity in the context of modern electronic health systems lacks robust evidence. Objective: This study aimed to assess the frequency of interventions performed by a second pharmacist to determine the ongoing effectiveness of the SPV process. Methods: This retrospective chart review was conducted at the Mayo Clinic, encompassing all anticancer therapy orders that necessitated an SPV. The study period extended from January 1, 2019, to June 30, 2021, and included inpatient and outpatient anticancer orders. The quantification and reporting of alterations made to discrete order fields subsequent to initial pharmacist verification of clinical significance were performed, utilizing the total number of anticancer therapy orders as the denominator. Results: Approximately 300 000 anticancer therapy orders were screened for inclusion criteria and 2.6% (N = 7634) of orders were modified on the SPV. Most changes were in the categories of rate (N = 1962), order start time (N = 1219), and pharmacy communication note (N = 777). Dosing changes greater than 10% accounted for 0.03% (N = 99) of the orders, with 10 anticancer therapies responsible for more than 50% of these changes. Conclusion and relevance: This study represents the largest report on the impact of SPV in a modern era. Our results suggest the SPV may be valuable for a small proportion of chemotherapy orders but raises questions about the necessity for broad application of this practice.

8 Background: At Mayo Clinic, the implementation of an automated chemotherapy dose rounding program has resulted in significant cost savings when doses are rounded down to a vial size, however, the cost burden from drug waste continues to be a significant issue when rounding to a vial size is not within our 10% rounding allowance. The mismatch between drug doses and the marketed vial sizes, along with the limitations to the use of single dose vials is a recognized problem, resulting in billions of dollars of wasted drugs in the United States.The goal of our study was to quantify the cost of the wasted amount of chemotherapy and biologic drugs after the implementation of an automated dose rounding program. Methods: Using the electronic health record (EHR), data was collected for biologic and oncolytic agents administered from 1/1/2019 through 12/31/2021. Drugs with waste documented during preparation and that were administered to cancer patients were selected for analysis. The % of doses with waste documented was calculated based upon the total number of all doses given. The total cost of the drug administered along with the cost of the amount of drug wasted were calculated based upon costs listed in the EHR at the time of administration. Results: For the 3-year period, 446,832 doses were dispensed with 47,626 (10.7%) of those doses having waste documented. The total cost of the drugs with documented waste was $114,323,203 with 21.9% ($25,086,608) accounting sole for wasted drug. Five drugs accounted for 59% of the total cost of the drug waste (Table). When examining individual drugs with a high % of doses with documented waste, methoxsalen, epirubicin, eribulin, topotecan, & bortezomib each had > 70% of doses with a documented wasted amount. Conclusions: Despite having an aggressive institutional dose rounding policy, drug waste still results in considerable and significant costs to the Mayo Clinic System. Our data likely underestimates the total cost of drugs waste given that waste documentation requires manual entry into the EHR at the time of preparation. Our results support the need to create and develop solutions that could lead to reduced waste costs which include re-examining the weight based dosing of drugs, mandating pharmaceutical companies to have vial sizes that more appropriately meet the range of standard dosing, developing more multi-dose vials that can be shared across multiple patients, utilizing closed-system transfer devices to extend beyond-use-dating time, or requiring pharmaceutical companies to reimburse payers and patients for the cost of the amount wasted. Drug waste is still a considerable issue and one that needs to be addressed at a policy level.[Table: see text]