Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review.

OBJECTIVE: To review the pharmacokinetic (PK)-pharmacodynamic (PD) profiles, disease setting, dosing, and safety of oral and parenteral hypomethylating agents (HMAs) for the treatment of myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML), and to provide a multidisciplinary perspective on treatment selection and educational needs relating to HMA use. DATA SOURCES: Clinical and real-world data for parenteral decitabine and azacitidine and two oral HMAs: decitabine-cedazuridine (DEC-C) for MDS and azacitidine (CC-486) for AML maintenance therapy. DATA SUMMARY: Differences in the PK-PD profiles of oral and parenteral HMA formulations have implications for their potential toxicities and planned use. Oral DEC-C (decitabine 35 mg and cedazuridine 100 mg) has demonstrated equivalent systemic area under the concentration-time curve (AUC) exposure to a 5-day regimen of intravenous (IV) decitabine 20 mg/m2 and showed no significant difference in PD. The AUC equivalence of oral DEC-C and IV decitabine means that these regimens can be treated interchangeably (but must not be substituted within a cycle). Oral azacitidine has a distinct PK-PD profile versus IV or subcutaneous azacitidine, and the formulations are not bioequivalent or interchangeable owing to differences in plasma time-course kinetics and exposures. Clinical trials are ongoing to evaluate oral HMA combinations and novel oral HMAs, such as NTX-301 and ASTX030. CONCLUSIONS: Treatment with oral HMAs has the potential to improve quality of life, treatment adherence, and disease outcomes versus parenteral HMAs. Better education of multidisciplinary teams on the factors affecting HMA treatment selection may help to improve treatment outcomes in patients with MDS or AML.

Expanding Pharmacy Services to the Hemophilia Treatment Center.

Background: Hemophilia treatment centers (HTC) are multidisciplinary clinics that serve as medical homes for patients with hemophilia and other bleeding or clotting disorders. Traditionally, hemophilia treatment center teams have included hematologists, social workers, nurse coordinators, physical therapists, and in some instances, other healthcare professionals. Objective: This report describes the role of clinical pharmacy services added at 2 HTCs. Method: Retrospective review of services provided by pharmacists integrated into the care team conducted at 2 HTCs. Conclusions: Pharmacists have the knowledge and training to positively contribute to the care of hemophilia treatment center patients. Specifically, with expertise in therapeutic drug monitoring, pharmacokinetics and patient counseling, pharmacists have the ability to manage the cost of care by promoting adherence, minimizing emergency department visits, and assisting providers in formulating optimal treatment plans to improve care for this patient population.

Which hematology/oncology patients are high priority for ambulatory clinical pharmacist review? A three-round Delphi survey by the National Comprehensive Cancer Network.

INTRODUCTION: Prioritization and acuity tools have been leveraged to facilitate targeted and efficient clinical pharmacist interventions. However, there is a lack of established pharmacy-specific acuity factors in the ambulatory hematology/oncology setting. Therefore, National Comprehensive Cancer Network's Pharmacy Directors Forum conducted a survey to establish consensus on acuity factors associated with hematology/oncology patients that are high priority for ambulatory clinical pharmacist review. METHODS: A three-round electronic Delphi survey was conducted. During the first round, respondents were asked an open-ended question to suggest acuity factors based on their expert opinion. Respondents were then asked in the second round to agree or disagree with the compiled acuity factors, in which those with ≥75% agreement were included in the third round. The final consensus was defined as a mean score ≥3.33 on a modified 4-point Likert scale (4 = strongly agree, 1 = strongly disagree) during the third round. RESULTS: A total of 124 hematology/oncology clinical pharmacists completed the first round of the Delphi survey (invitation response rate, 36.7%), of which 103 completed the second round (response rate, 83.1%) and 84 the third round (response rate, 67.7%). A final consensus was achieved for 18 acuity factors. Acuity factors were identified in the following themes: antineoplastic regimen characteristics, drug interactions, organ dysfunction, pharmacogenomics, recent discharge, laboratory parameters, and treatment-related toxicities. CONCLUSIONS: This Delphi panel of 124 clinical pharmacists achieved consensus on 18 acuity factors that would identify a hematology/oncology patient as a high priority for ambulatory clinical pharmacist review. The research team envisions incorporating these acuity factors into a pharmacy-specific electronic scoring tool.

Cost comparison of filgrastim versus pegfilgrastim and pegfilgrastim biosimilars for inpatient prophylaxis of febrile neutropenia.

INTRODUCTION: The Ohio State University Comprehensive Cancer Center (The James) uses daily subcutaneous filgrastim as the inpatient granulocyte colony-stimulating factor of choice. The coordination of care associated with filgrastim can often be a barrier to patient discharge. The purpose of this study was to compare the inpatient cost of daily filgrastim to single dose pegfilgrastim and biosimilars. METHODS: Adult patients admitted to The James who received at least one dose of filgrastim between June 1, 2021 and August 31, 2021 were retrospectively identified. This study compared the inpatient cost of filgrastim and biosimilars associated with one chemotherapy cycle to the potential inpatient cost of pegfilgrastim and biosimilars based on average sales price (ASP). Additionally, the number and duration of discharge prescriptions for filgrastim was determined. RESULTS: Of the 44 unique patient encounters that met inclusion criteria, 19 received 300-mcg doses of filgrastim and 25 received 480-mcg doses. The median number of doses administered per admission was eight. If each of these patients were to instead receive the most inexpensive biosimilar, pegfilgrastim reference product, the cost would be 216% higher than with filgrastim-sndz. At discharge, 15 patients (34%) received a prescription for filgrastim to be continued for a median duration of 6 days. CONCLUSION: Based on ASP, pegfilgrastim was more costly than filgrastim. Potential rebates and negotiation power may alter the financial outlook of adding pegfilgrastim to inpatient formulary. Exploration of delays in discharge due to insurance coordination for filgrastim continuation in the outpatient setting may also impact formulary decisions.

Pharmacy utilization of electronic patient-reported outcomes in oncology populations.

Telehealth applications are demonstrated to be useful tools for patients with cancer to facilitate improvements in quality of care. The use of electronic patient-reported outcomes is one way to leverage telehealth to better understand outcomes important to patients. However, use of electronic patient-reported outcomes and direct involvement of pharmacists is not yet a standard practice across cancer centers. The use of pharmacist-led telehealth services offers a unique opportunity for pharmacists to provide cost-effective and convenient patient care interventions. This survey work describes the current practices of pharmacy utilization of electronic patient-reported outcomes in oncology populations at National Comprehensive Cancer Network member institutions. Of survey respondents, only 33% of the institutions reported current engagement with electronic patient-reported outcomes. These initiatives largely focused on symptom management. Limitations in staff, resources, and competing priorities limit many institutions from introducing or expanding upon direct pharmacist involvement in electronic patient-reported outcomes. Further work developing the involvement of pharmacists in electronic patient-reported outcomes will be an important way to leverage the growing landscape of telehealth within oncology and highlight the value of the pharmacist.

Description of the role of pharmacist independent double checks during cognitive order verification of outpatient parenteral anti-cancer therapy.

INTRODUCTION: To describe pharmacist interventions as a result of an independent double check during cognitive order verification of outpatient parenteral anti-cancer therapy. METHODS: A single-center, retrospective analysis of all individual orders for outpatient, parenteral anti-cancer agents within a hematology/oncology infusion center during a 30 day period was conducted. The primary endpoint was error identification rates during first and second verification. Secondary endpoints included the type, frequency, and severity of errors identified during second verification using a modified National Coordinating Council for Medication Error Reporting and Prevention Index. RESULTS: A total of 1970 anti-cancer parenteral orders were screened, from which 1645 received an independent double check and were included. The number of errors identified during first and second verification were 30 (1.8%) and 10 (0.6%) respectively; second verification resulted in a 33.3% increase in corrected errors. The 10 errors identified during second verification included: four rate transcriptions to optimize pump interoperability, three rate and/or volume modifications, two dosage adjustments, and one treatment deferral due to toxicity. The severity was classified as Category A for four (40%), Category C for three (30%), and Category D for three (30%) errors. This correlated to a low capacity for harm for seven (70%) and a serious capacity for three (30%) errors. CONCLUSIONS: Second verification of outpatient, parenteral anti-cancer medication orders resulted in a 33.3% increase in corrected errors. Three errors detected during second verification were determined to have a serious capacity for harm, supporting the value of independent double checks during pharmacist cognitive order verification.

Costs associated with United States pharmacopeia compliant infusion clinics.

PURPOSE: As costs continue to rise in oncology, a strategy that has been implemented to limit these costs is use of alternative sites of care. However, there are differences in regulatory standards between common sites of care such as freestanding infusion clinics and hospital outpatient departments. The costs associated with United States Pharmacopeia compliance were evaluated in order to better understand the cost of universally compliant hospital outpatient departments. METHODS: Annual operational costs associated with United States Pharmacopeia compliance were estimated for a 30-chair infusion clinic with United States Pharmacopeia <797> and <800> pharmacy cleanrooms for non-hazardous and hazardous drugs, respectively. Annual United States Pharmacopeia compliance costs included: competency assessments, personal protective equipment, closed system transfer devices, labels, cleaning supplies, and environmental monitoring. One-time costs included initial cleanroom construction and renovations. Published information and benchmarks provided baseline assumptions for patient volume, staffing, and unit costs. If no published data was available, prices were estimated based on a similarly sized clinic. RESULTS: Recurring annual costs for a 30-chair fully compliant infusion clinic were calculated to be $785,207. One-time costs associated with initial construction and renovations were estimated to be $1,365,207-$1,535,207 and $965,207-$1,005,207, respectively. CONCLUSIONS: Costs associated with increased operational oversight and regulatory standards are a major contributing factor to the facility fee of hospital outpatient departments. Ultimately, all sites of care share in the goal to provide optimal patient care while considering all aspects of patient care, including cost. Therefore, a move towards consistent regulatory standards across all settings would aid in preventing discrepancies in care.

The formulary process for biosimilar additions at a comprehensive cancer center.

Biological products may be used to diagnose, prevent, treat, and cure diseases and medical conditions, including cancer. Biosimilar agents, approved under an abbreviated 351(k) pathway, continue to increase in number and market share for biologic agents, especially for cancer care. Although biosimilars offer the potential for improved access to care, their introduction to the marketplace has created significant disruption. It is imperative that health systems providing care to patients with cancer develop a well-defined process to address the challenges associated with biosimilars. This descriptive article outlines pharmacy considerations for biosimilars and describes the current practices at The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at The Ohio State University. Biosimilars have and will continue to significantly impact oncology care. Organizations must understand the clinical, operational, and financial challenges associated with the use of these products.

Coronavirus 2019 work-from-home productivity of inpatient and infusion pharmacists at a comprehensive cancer center.

PURPOSE: To evaluate inpatient and infusion pharmacist order verification productivity when working from home and to report their perceptions of a flexible workplace setting. METHODS: Order verification data were pulled from the electronic medical record from April 27, 2020, to June 30, 2020, matched to the pharmacist schedule on the basis of work setting and reported as average orders verified per day. Pharmacist perceptions were gathered via a survey to evaluate practice setting background, workplace setting preference, and perceived changes in workflow and their productivity. RESULTS: There was an overall increase in order verification productivity when working from home. Inpatient pharmacists, on average, verified 152 orders per day from home and 133 orders per day onsite. Infusion pharmacists, on average, verified 144 orders per day working from home and 117 orders per day working onsite. Fifty-nine percent of pharmacists reported preferring the mix of onsite and home workplace setting and noted little change in workflow. In addition, 57% of the pharmacists perceived themselves as being more productive, 32% as maintaining the same level of productivity, and 10% felt that they are less productive when working from home. The order verification data showed a greater increase in productivity for infusion shifts worked from home than inpatient shifts. CONCLUSION: The coronavirus 2019 pandemic prompted pharmacy departments to re-evaluate their ability to provide an option for a flexible workplace for pharmacists. Our study demonstrates that pharmacists, on average, verified more orders when working from home, and they also perceive themselves as being more productive. The results of this study support long-term applicability of a flexible work schedule for inpatient and infusion pharmacists.

Computer Vision in the Operating Room: Opportunities and Caveats.

Effectiveness of computer vision techniques has been demonstrated through a number of applications, both within and outside healthcare. The operating room environment specifically is a setting with rich data sources compatible with computational approaches and high potential for direct patient benefit. The aim of this review is to summarize major topics in computer vision for surgical domains. The major capabilities of computer vision are described as an aid to surgical teams to improve performance and contribute to enhanced patient safety. Literature was identified through leading experts in the fields of surgery, computational analysis and modeling in medicine, and computer vision in healthcare. The literature supports the application of computer vision principles to surgery. Potential applications within surgery include operating room vigilance, endoscopic vigilance, and individual and team-wide behavioral analysis. To advance the field, we recommend collecting and publishing carefully annotated datasets. Doing so will enable the surgery community to collectively define well-specified common objectives for automated systems, spur academic research, mobilize industry, and provide benchmarks with which we can track progress. Leveraging computer vision approaches through interdisciplinary collaboration and advanced approaches to data acquisition, modeling, interpretation, and integration promises a powerful impact on patient safety, public health, and financial costs.

Towards an AI Coach to Infer Team Mental Model Alignment in Healthcare.

Shared mental models are critical to team success; however, in practice, team members may have misaligned models due to a variety of factors. In safety-critical domains (e.g., aviation, healthcare), lack of shared mental models can lead to preventable errors and harm. Towards the goal of mitigating such preventable errors, here, we present a Bayesian approach to infer misalignment in team members' mental models during complex healthcare task execution. As an exemplary application, we demonstrate our approach using two simulated team-based scenarios, derived from actual teamwork in cardiac surgery. In these simulated experiments, our approach inferred model misalignment with over 75% recall, thereby providing a building block for enabling computer-assisted interventions to augment human cognition in the operating room and improve teamwork.

Describing the role of the hematology/oncology clinical pharmacist in health information technology.

PURPOSE: To describe the role of hematology/oncology clinical pharmacists in health information technology as well as their perceptions of the impact of technology expansion on patient care. METHODS: A single-center, web-based survey was distributed to 30 hematology/oncology clinical pharmacists by email over the two-week-period of 24 September 2018 to 8 October 2018. The anonymous survey was composed of 19 questions, with varying formats including multiple choice, fill-in-the-blank, and rank order. Primary endpoints were quantification of time spent in the electronic health record and perceptions on how technology expansion has impacted the safety, quality, and efficiency of patient care. RESULTS: Twenty-seven hematology/oncology clinical pharmacists (90% response rate) completed the survey in its entirety. Respondents reported that they spend an average of 84.1% of their work day in the electronic health record. Based on a 40-h work week, clinical pharmacists indicated that they spend approximately 32.2 h each week performing direct patient care tasks in the electronic health record compared to 3.7 h on indirect patient care tasks. All respondents reported a greater utilization of technology over the last five years, and most respondents felt that patient care is safer, of better quality, and more efficient with technology expansion. The majority of respondents (81.5%) indicated that clinical pharmacists have the best understanding of the health information technology system, followed by generalist pharmacists and informatics pharmacists. CONCLUSION: The hematology/oncology clinical pharmacist is well positioned to serve as a health information technology leader on the interdisciplinary healthcare team.

Development and Implementation of an Oral Oncology Drug Repository Program.

PURPOSE: Because of high costs associated with oral oncology drugs, patients are often unable to afford their medications. Developing and implementing an oral oncology drug repository program can provide cost savings and waste reduction opportunities to oncology patients and health care systems. METHODS: Strategies to implement an oral oncology drug repository program include the following: (1) define patient eligibility requirements for the collected drug, (2) ensure patients have long-term availability to preferred treatment, (3) identify optimal oral oncology drugs to use, (4) provide safe drug collection with protocol, (5) calculate the amount of resources needed to provide services, (6) obtain adequate space to operate safely and efficiently, (7) establish safe disposal of the drug deemed inappropriate for use, and (8) spread awareness to prospective patient participants. RESULTS: To date, The Ohio State University Wexner Medical Center oral oncology drug repository program has received 11 drug collections and has redispensed drugs several times. With additional resources, the plan is to expand the repository program's scope to include other drugs and reach more patients. CONCLUSION: Developing and implementing an oral oncology drug repository program for patients was logistically feasible due to strategic planning with many early successes. As national attention continues to be placed on reducing oral oncology drug costs, additional research is needed regarding strategies to best incorporate pharmacy services into innovative patient care opportunities.

Artificial intelligence in cardiothoracic surgery.

The tremendous and rapid technological advances that humans have achieved in the last decade have definitely impacted how surgical tasks are performed in the operating room (OR). As a high-tech work environment, the contemporary OR has incorporated novel computational systems into the clinical workflow, aiming to optimize processes and support the surgical team. Artificial intelligence (AI) is increasingly important for surgical decision making to help address diverse sources of information, such as patient risk factors, anatomy, disease natural history, patient values and cost, and assist surgeons and patients to make better predictions regarding the consequences of surgical decisions. In this review, we discuss the current initiatives that are using AI in cardiothoracic surgery and surgical care in general. We also address the future of AI and how high-tech ORs will leverage human-machine teaming to optimize performance and enhance patient safety.

Development of a tool to allocate inpatient specialized pharmacy resources at a comprehensive cancer center.

PURPOSE: Develop an objective tool to align the needs of inpatient services at a Comprehensive Cancer Center with the available resources of hematology/oncology clinical specialist pharmacists. SUMMARY: The shift of the pharmacy profession from product-centered to patient-centered care has expanded the scope of practice of the clinical pharmacist and their ability to specialize in a therapeutic area. However, these specialized resources are limited. The pharmacy department at The James Comprehensive Cancer Center at The Ohio State University Wexner Medical Center developed a tool to objectively determine which inpatient services would receive the most benefit from having a hematology/oncology clinical specialist pharmacist on their healthcare team. A Steering Committee was created to determine the necessary metrics needed across the 29 inpatient services at The James, and data was collected from the electronic medical record. The metrics evaluated were: patient acuity, inpatient intravenous anticancer administrations, inpatient oral anticancer administrations, presence of an outpatient anticancer treatment plan for patients admitted for an inpatient stay, and the use of high-risk hematology/oncology therapies. CONCLUSION: A novel and data-driven tool was created to allocate hematology/oncology clinical specialist pharmacists across a Comprehensive Cancer Center. Annual use of this objective tool can aid institutions in appropriate distribution of limited hematology/oncology specialized pharmacy resources.

The pharmacist's role in chimeric antigen receptor T cell therapy.

The emergence and efficacy of chimeric antigen receptor (CAR) T cell therapy in previously incurable malignancies represents a promising paradigm shift in cancer care. However, it is not without significant clinical, operational, and financial considerations. Pharmacists should be prepared to fulfill the various roles in CAR T cell therapy provision including: policy development; electronic medical record build; patient and staff education; patient selection; procurement, storage, and handling; medication administration and supportive care; management of adverse reactions; and quality tracking. Our commentary provides an overview of the opportunities for pharmacy involvement in the implementation and maintenance of a CAR T cell therapy program with an emphasis on the importance of pharmacy involvement as part of a multidisciplinary approach to care. Although some institutions have dedicated a CAR T cell pharmacist to meet the demands of emerging CAR T cell therapy, we believe that clinical pharmacists practicing in hematopoietic stem cell transplant and hematology/oncology have the skills and training to fulfill the pharmacist's role in CAR T cell therapy.

Front-line use of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia: Practice considerations.

The development of BCR-ABL-targeting tyrosine kinase inhibitors has transformed chronic phase chronic myeloid leukemia (CP CML) from a disease with a terminal prognosis to a treatable chronic illness. Long-term treatment with tyrosine kinase inhibitors means that patients have to be clinically managed and monitored over extended periods of time, thus a patient-centered, medically integrated, and multidisciplinary oncology healthcare team is required to support patients through their journey. Pharmacists work with patients, physicians, and the wider support team to select the optimum therapy plan for a given patient. These decisions are based on risk factors, comorbidities, concomitant medications, and personal circumstances and pharmacists advise on the efficacy and safety of different treatment options. Additionally, pharmacists are a key point-of-contact and resource for monitoring patient response to treatment, identifying and managing adverse events and drug-drug interactions, any subsequent therapy plan modifications, and, potentially, treatment-free remission. Pharmacists also assist with patient education, medication adherence, and financial discussions with patients throughout the long course of the disease. This review provides an overview of BCR-ABL tyrosine kinase inhibitors, discusses the role of the medically integrated pharmacy team, and suggests strategies that pharmacists can use in patient management and clinical decision-making to optimize the treatment of CP CML.

Demonstrating the value of the oncology pharmacist within the healthcare team.

INTRODUCTION: Although many oncology pharmacists are embedded members within the healthcare team, data documenting their contributions to optimal patient outcomes are growing. The purpose of this paper is to demonstrate the value of the oncology pharmacist within the healthcare team and describe the knowledge, skills, and functions of the oncology pharmacist. METHODS: A systematic literature review of articles that were published on PubMed between January 1951 and October 2018 was completed. Identified abstracts were reviewed and included if they focused on measuring the value or impact of the oncology pharmacist on provider/patient satisfaction, improvement of medication safety, improvement of quality/clinical care outcomes, economics, and intervention acceptance. Review articles, meta-analysis, and studies not evaluating oncology pharmacist activities were excluded. Studies were thematically coded into four themes (clinical care, patient education, informatics, and cost savings) by 10 oncology pharmacists. RESULTS: Four-hundred twenty-two articles were identified, in which 66 articles met inclusion criteria for this review. The selected literature included 27 interventional and 38 descriptive studies. The value of the oncology pharmacist was demonstrated by published articles in four key themes: clinical care, patient education, informatics, and cost savings. CONCLUSION: With an expected shortage of oncology physicians and the ongoing development of complex oncology therapies, the board-certified oncology pharmacist is well suited to serve as a physician extender alongside nurse practitioners and/or physician assistants as the medication expert on the oncology care team. The demonstrated value of the oncology pharmacist supports their role as frontline providers of patient care.

Queueing theoretic analysis of labor and delivery : Understanding management styles and C-section rates.

Childbirth is a complex clinical service requiring the coordinated support of highly trained healthcare professionals as well as management of a finite set of critical resources (such as staff and beds) to provide safe care. The mode of delivery (vaginal delivery or cesarean section) has a significant effect on labor and delivery resource needs. Further, resource management decisions may impact the amount of time a physician or nurse is able to spend with any given patient. In this work, we employ queueing theory to model one year of transactional patient information at a tertiary care center in Boston, Massachusetts. First, we observe that the M/G/∞ model effectively predicts patient flow in an obstetrics department. This model captures the dynamics of labor and delivery where patients arrive randomly during the day, the duration of their stay is based on their individual acuity, and their labor progresses at some rate irrespective of whether they are given a bed. Second, using our queueing theoretic model, we show that reducing the rate of cesarean section - a current quality improvement goal in American obstetrics - may have important consequences with regard to the resource needs of a hospital. We also estimate the potential financial impact of these resource needs from the hospital perspective. Third, we report that application of our model to an analysis of potential patient coverage strategies supports the adoption of team-based care, in which attending physicians share responsibilities for patients.