Edaravone in the treatment of amyotrophic lateral sclerosis: efficacy and access to therapy - a roundtable discussion.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease affecting approximately 5 out of every 100,000 individuals living in the United States. ALS is associated with 50% mortality within 30 months of initial symptom onset. The rarity of the disease, along with the significant inter- and intra-patient variability in clinical course and a lack of reliable biomarkers, have rendered the development of effective agents to treat ALS a challenge. Because oxidative stress is considered a contributing factor to ALS onset and progression, drugs that eliminate free radicals may protect motor neurons from damage potentially caused by free-radical and oxidative stress. Edaravone is an antioxidant free-radical scavenger approved by the FDA in 2017 for the treatment of ALS. A review of the edaravone clinical development program offers a clearer view of the clinical utility of this agent. Broader treatment success is also influenced by factors such as limited patient access and the restrictive payer environment. Cooperation within the healthcare community, among clinicians, patient advocacy groups, pharmaceutical companies, and managed care payers, must occur to advance ALS management and treatment and improve patient access. Moreover, collaborative discussions are useful in identifying potential solutions to problems currently surrounding patient access.

Building a business case for an outpatient pharmacy.

To be successful, an outpatient prescription pharmacy service built and operated by a hospital should be run as a competitive business, not in the manner of an inpatient operation. The outpatient pharmacy should not be a siloed entity that operates separately from the inpatient pharmacy. A hospital may miss a significant margin opportunity if it runs the pharmacy strictly as a safety net for uninsured or underinsured patients.

Budget impact analysis of insulin therapies and associated delivery systems.

PURPOSE: A budget impact analysis of insulin therapies and associated delivery systems is presented. METHODS: Based on inputted procurement totals, per-item costs (based on 2011 average wholesale price), insulin distribution system (floor stock or individual patient supply), waste, and treatment protocols for a specified time frame, the budget impact model approximated the number of patients treated with subcutaneous insulin, costs, utilization, waste, and injection mechanism (pen safety needle or syringe) costs. To calculate net changes, results of one-year 3-mL vial use were subtracted from one-year 10-mL vial or 3-mL pen use. RESULTS: Switching from a 10-mL vial to a 3-mL vial was associated with reductions in both costs and waste. The net reductions in costs and waste ranged from $15,482 and 120,000 IU, respectively, for floor-stock 10-mL vial to floor-stock 3-mL vial conversion to $871,548 and 6,750,000 IU, respectively, for individual patient supply 10-mL vial to floor-stock 3-mL vial conversion. Switching from floor-stock 10-mL vials to individual patient supply 3-mL vials increased costs and waste by $164,659 and 1,275,000 IU, respectively. Converting from individual patient supply 3-mL pens to individual patient supply 3-mL vials reduced costs by $117,236 but did not decrease waste. CONCLUSION: A budget impact analysis of the conversion of either 10-mL insulin vials or 3-mL insulin pens to 3-mL insulin vials found reductions in both cost and waste, except when converting from floor-stock 10-mL vials to individual patient supply 3-mL vials.

Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device.

PURPOSE: Surface contamination with the antineoplastic drugs cyclophosphamide, ifosfamide, and 5-fluorouracil was compared in 22 US hospital pharmacies following preparation with standard drug preparation techniques or the PhaSeal® closed-system drug transfer device (CSTD). METHODS: Wipe samples were taken from biological safety cabinet (BSC) surfaces, BSC airfoils, floors in front of BSCs, and counters and analyzed for contamination with cyclophosphamide, ifosfamide, and 5-fluorouracil. Contamination was reassessed several months after the implementation of the CSTD. Surface contamination (ng/cm(2)) was compared between the two techniques and evaluated with the Signed Rank Test. RESULTS: Using the CSTD compared to the standard preparation techniques, a significant reduction in levels of contamination was observed for all drugs (cyclophosphamide: p < 0.0001; ifosfamide: p < 0.001; 5-fluorouracil: p < 0.01). Median values for surface contamination with cyclophosphamide, ifosfamide, and 5-fluorouracil were reduced by 95%, 90%, and 65%, respectively. CONCLUSIONS: Use of the CSTD significantly reduces surface contamination when preparing cyclophosphamide, ifosfamide, and 5-fluorouracil as compared to standard drug preparation techniques.

Establishing an anemia clinic for optimal erythropoietic-stimulating agent use in hematology-oncology patients.

Erythropoietic-stimulating agent (ESA) therapy has significantly impacted the management of chemotherapy-induced anemia (CIA) by decreasing the number of red blood cell transfusions required by patients with cancer. However, managing these patients with ESA therapy has become increasingly difficult since the release of the Centers for Medicare & Medicaid Services' new National Coverage Determination document because of the disparities between this document and recommendations from expert-reviewed national clinical guidelines on the treatment of anemia. This article describes a collaborative practice agreement between pharmacists and physicians as one approach to managing CIA in hematology-oncology patients in an anemia clinic. The goal of the pharmacist-managed anemia clinic is to improve patient satisfaction and clinical outcomes associated with the treatment of CIA. This article describes the rationale for the clinic and discusses its design and implementation in managing ESA, iron, folate, and vitamin B12 therapy for CIA in hematology-oncology patients. The pharmacist's role is justified in this clinic model through increased adherence to evidence-based practice guidelines and decreased costs associated with ESA therapy.

Continued challenges with the use of erythropoiesis-stimulating agents in patients with cancer: perspectives and issues on policy-guided health care.

Erythropoiesis-stimulating agents (ESAs) are approved as an alternative to blood transfusions for treating anemia secondary to chemotherapy in patients with cancer. Recently, ESAs have been a source of controversy and confusion in the oncology community. This began when two European trials-the Breast Cancer Erythropoietin Survival Trial (BEST) and the Advanced Head-and-Neck Cancer Treated with Radiotherapy (ENHANCE) Study-raised safety concerns about decreased overall survival and increased venous thromboembolic events. In 2004, the United States Food and Drug Administration (FDA) convened its Oncologic Drugs Advisory Committee (ODAC) to review the data and reassess the risks and benefits of ESAs in patients with cancer. On May 10, 2007, ODAC reconvened when five trials (BEST, ENHANCE, AMG-20010103, AMG-20000161, and EPO-CAN-20) showed decreased overall survival. The briefing document noted that studies demonstrating detrimental effects on survival and/or tumor outcomes used an unapproved treatment regimen designed to maintain hemoglobin levels above 12 g/dl. On May 14, 2007, just days after the ODAC reconvened, the Centers for Medicare and Medicaid Services (CMS) released a proposed decision memo for a national coverage determination (NCD) imposing restrictions on ESAs. For health care providers, aspects of the proposed NCD were markedly inconsistent with FDA-approved ESA use and generally were considered ambiguous and unclear. Over objections of several professional associations and members of Congress, on July 30, 2007, CMS posted the final NCD and declared it effective immediately. When compared with FDA-approved labeling and professional society guidelines, the NCD revealed differences in ESA initiation, dosage escalation, dosage reduction, and definition of response. These discrepancies have generated confusion among health care providers, who are struggling over whether they can feasibly provide a dual system of care-one for Medicare patients and another for non-Medicare patients-that is evidence based. With this supplement, we hope to educate health care providers on the issues and challenges associated with policy-guided health care when discrepancies exist between the policy and evidence-based practice; offer guidance on implementing the NCD; and highlight the important role of pharmacists in the process.

Documentation of chemotherapy infusion preparation costs in academic- and community-based oncology practices.

Significant changes in Medicare reimbursement for outpatient oncology services were proposed as part of the Medicare Modernization Act of 2003. The purpose of this study was to identify the "true cost" associated with drug-related handling for the preparation and delivery of chemotherapy doses to estimate the impact of changing reimbursement schema by Medicare. Two academic medical outpatient infusion centers and 2 community cancer centers provided data used to estimate all costs (excluding drug cost) associated with the preparation of chemotherapy doses. The data included both fixed costs (drug storage, space, equipment, and information resources) and variable costs (insurance management, inventory, waste management, pharmacy staff payroll, supplies, and shipping). The average cost for the preparation of chemotherapy doses across all sites was dollar 34.27 (range, dollar 32.08-dollar 41.23). A time-and-motion study was also performed to determine what tasks were conducted by pharmacy staff and how much time was spent in the preparation of the top 15 chemotherapeutic drugs and regimens used in the 4 sites. Data from the 4 centers was projected to show that if 3,990,495 million chemotherapy infusions were administered to a national Medicare population in 2003, when multiplied by the average cost of preparation for infusions determined by the current study (dollar 34.27), the estimated total annual cost to Medicare for chemotherapy preparation by pharmacists is dollar 136,754,263.65. The pharmacists spent most of their days (90% or more) performing tasks directly related to the preparation of these agents. These data provide scientific support for the consideration of appropriate reimbursement for chemotherapy services provided by pharmacists to Medicare beneficiaries.

International harmonization of generic drugs: in vitro dissolution tests for Japanese and American generic tablets.

Ibuprofen tablets on the market in Japan and the USA were compared by manual- and automatic-dissolution tests according to USP24 criteria. Dissolution test were performed in 900 ml of phosphate buffer of pH 7.2 at 37.0+/-0.5 degrees C at 50 rpm for 60 min, and the time required for 70% dissolution (T70%) and 5% dissolution after 60 min (A60) were evaluated. The dissolution profiles of both Japanese and American tablets by the automatic-method showed almost the same profiles as those of the manual method. T70% of the American and Japanese tablets by the manual method were not significantly different (p>0.05) from the automatic-method at various sampling positions. The A60 of the American and Japanese tablets by the manual-method was not significantly different (p>0.05) except at one position. The results indicate that the automatic-method was more reproducible than the manual-method, and also that systematic error was negligible. The T70% and A60 of the American tablets were significantly different (p<0.05) from the Japanese tablets. The American tablets were a film-coated over-the-counter drug and the Japanese tablets were a sugar-coated prescription drug. There was a difference in dissolution behavior between the dosage forms of the two countries.

Benefit of ribose in a patient with fibromyalgia.

Ribose was added to the existing treatment regimen of a woman with fibromyalgia, resulting in a decrease in symptoms. It has been postulated that patients with fibromyalgia may have an alteration in muscle adenine nucleotide metabolism, leading to depleted energy reserves and an imbalance in cellular adenosine 5'-triphosphate:adenosine 5'-diphosphate:adenosine 5'-monophosphate (ATP:ADP:AMP) ratios with an abnormal energy charge. As a key component in adenine nucleotide synthesis, ribose supplementation may be useful in such patients.

Using a closed-system protective device to reduce personnel exposure to antineoplastic agents.

Surface contamination with and personnel exposure to antineoplastic agents before and after the implementation of a closed-system protective device were studied. Samples were collected before and six months after implementation of PhaSeal, a closed-system device for limiting exposure to antineoplastic agents during preparation and administration. Personnel exposure was evaluated by collecting 24-hour urine samples from pharmacists, pharmacy technicians, and nurses working full-time in a chemotherapy drug infusion center and pharmacy. Surface contamination was assessed by wiping potentially exposed surfaces. Both types of samples were analyzed for cyclophosphamide and ifosfamide by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. All 17 wipe samples collected before implementation of PhaSeal had detectable levels of cyclophosphamide, and 11 were positive for ifosfamide. Six months after system implementation, 7 of 21 wipe samples had detectable levels of cyclophosphamide and 15 were positive for ifosfamide. Of eight employees who provided urine samples, six were positive for cyclophosphamide and two for ifosfamide before implementation, and none were positive for either drug after implementation. The PhaSeal system appeared to reduce exposure of health care personnel to cyclophosphamide and ifosfamide.

Components of Medicare reimbursement.

The history of the Medicare reimbursement system, how it works, and issues related to fraud and abuse are discussed. The statutory charge of Medicare is to ensure adequate reimbursement through a Prospective Payment System (PPS) to cover the costs for providing a given service to Medicare beneficiaries. The PPS was introduced as a way to change hospital behavior through financial incentives that encourage cost-efficient management of resources. The system utilizes a rate of payment in which a hospital is paid a fixed amount that is expected to cover the costs of care while treating a typical patient in a particular diagnosis-related group (DRG). The PPS uses DRGs as payment categories and Major Diagnostic Categories (MDCs) for classifying the DRGs into similar groupings. One of the first steps in DRG assignment is identification of the principal diagnosis represented by an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code. The secondary diagnoses (referred to as complications or comorbidities), presence or absence of surgery, age of the patient, and discharge status are the other pieces of information making up assignment of a specific DRG to a patient. A basic knowledge of the Medicare program will help in the understanding of how hospitals will be reimbursed for patient care, as well as how changes in Medicare payment may affect reimbursement. Medicare is one of the largest health insurance providers in the United States. A basic understanding of the Medicare system will provide valuable insights into Medicare reimbursement and the influence it has on a hospital's bottom line.