Chemotherapy-induced febrile neutropenia (FN): healthcare resource utilization (HCRU) and costs in commercially insured patients in the US.

PURPOSE: Febrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per episode should be updated from real-world data. METHODS: A retrospective claims analysis of FN episodes in patients with non-myeloid malignancies from 2014 to 2021 was performed in IQVIA PharMetrics® Plus database. FN episodes were defined as having same-day claims for neutropenia and fever or infection, plus antibiotic in outpatient settings, following a claim for chemotherapy; index date was defined as the first claim for neutropenia/fever/infection. Patients receiving bone marrow/stem cell transplant and CAR-T therapy were excluded, as were select hematologic malignancies or COVID-19. Healthcare utilization and costs were evaluated and described overall, by episode type (w/wo hospitalization), index year, malignancy type, NCI comorbidity score, and age group. RESULTS: 7,033 FN episodes were identified from 6,825 patients. Most episodes had a hospitalization (91.2%) and 86% of patients had ≥1 risk factor for FN. Overall, FN episodes had a mean (SD) FN-related cost of $25,176 ($39,943). Episodes with hospitalization had higher average FN-related costs versus those without hospitalization ($26,868 vs $7,738), and costs increased with comorbidity score (NCI=0: $23,095; NCI >0-2: $26,084; NCI ≥2: $26,851). CONCLUSIONS: FN continues to be associated with significant economic burden, and varied by cancer type, comorbidity burden, and age. In this analysis, most FN episodes were not preceded by GCSF prophylaxis. The results of this study highlight the opportunity to utilize GCSF in appropriate oncology scenarios.

NCCN Biosimilars White Paper: regulatory, scientific, and patient safety perspectives.

Biologics are essential to oncology care. As patents for older biologics begin to expire, the United States is developing an abbreviated regulatory process for the approval of similar biologics (biosimilars), which raises important considerations for the safe and appropriate incorporation of biosimilars into clinical practice for patients with cancer. The potential for biosimilars to reduce the cost of biologics, which are often high-cost components of oncology care, was the impetus behind the Biologics Price Competition and Innovation Act of 2009, a part of the 2010 Affordable Care Act. In March 2011, NCCN assembled a work group consisting of thought leaders from NCCN Member Institutions and other organizations, to provide guidance regarding the challenges health care providers and other key stakeholders face in incorporating biosimilars in health care practice. The work group identified challenges surrounding biosimilars, including health care provider knowledge, substitution practices, pharmacovigilance, naming and product tracking, coverage and reimbursement, use in off-label settings, and data requirements for approval.

Spending on Antineoplastic Agents in the United States, 2011 to 2016.

PURPOSE:: Recent cancer drug approvals are lauded as being more effective with relatively fewer adverse effects, but these treatments come with a great cost to the US health care system. There is little information on recent trends in actual antineoplastic expenditures representative of the whole US health care system or by sector. Therefore, the objective of this study was to describe antineoplastic expenditures in the United States by year and sector. METHODS:: This was a retrospective, cross-sectional study of IQVIA (formerly QuintilesIMS) National Sales Perspective data for the period of January 1, 2011, to December 31, 2016. Actual expenditures were totaled by health care sector and calendar year, then adjusted for medical-cost inflation to 2016 dollars. Growth was calculated as the percentage increase from the previous year. RESULTS:: Total expenditures of antineoplastic agents across all channels grew from $26.8 billion in 2011 to $42.1 billion in 2016. Antineoplastic spending increased 12.2% in 2016 (compared with the previous year), followed by 15.6% in 2015, 13.4% in 2014, 6.3% in 2013, and 0.4% in 2012. Throughout the study period, 96.5% of total antineoplastic expenditures occurred within clinics, mail-order pharmacies, nonfederal hospitals, and retail pharmacies. CONCLUSION:: Antineoplastic expenditures are expected to increase because of continuing development and approval of costly targeted cancer therapies. Cost containment and utilization management strategies must be balanced so as not to restrict access or disrupt innovation. Future policies should focus on ensuring safe and appropriate use of antineoplastics while balancing long-term drug costs.

National trends in prescription drug expenditures and projections for 2018.

PURPOSE: Historical trends and factors likely to influence future pharmaceutical expenditures are discussed, and projections are made for drug spending in 2018 in nonfederal hospitals, clinics, and overall (all sectors). METHODS: Drug expenditure data through calendar year 2017 were obtained from the IQVIA (formerly QuintilesIMS) National Sales Perspectives database and analyzed. New drug approvals, patent expirations, and other factors that may influence drug spending in hospitals and clinics in 2018 were also reviewed. Expenditure projections for 2018 for nonfederal hospitals, clinics, and overall (all sectors) were made based on a combination of quantitative analyses and expert opinion. RESULTS: Total U.S. prescription sales in the 2017 calendar year were $455.9 billion, a 1.7% increase compared with 2016. The top drug based on expenditures was adalimumab ($17.1 billion), followed by insulin glargine and etanercept. Prescription expenditures in nonfederal hospitals totaled $34.2 billion, a 0.7% decrease in 2017 compared with 2016. Expenditures in clinics increased 10.9%, to a total of $70.8 billion. The decrease in spending in nonfederal hospitals was driven by lower utilization. The top 25 drugs by expenditures in nonfederal hospitals and clinics were dominated by specialty drugs. CONCLUSION: We project a 3.0-5.0% increase in total drug expenditures across all settings, a 11.0-13.0% increase in clinics, and a 0.0-2.0% increase in hospital drug spending in 2018. Health-system pharmacy leaders should carefully examine their own local drug utilization patterns to determine their own organization's anticipated spending in 2018.

National trends in prescription drug expenditures and projections for 2017.

PURPOSE: Historical trends and factors likely to influence future pharmaceutical expenditures are discussed, and projections are made for drug spending in 2017 in nonfederal hospitals, clinics, and overall (all sectors). METHODS: Drug expenditure data through calendar year 2016 were obtained from the QuintilesIMS National Sales Perspectives database and analyzed. Other factors that may influence drug spending in hospitals and clinics in 2017, including new drug approvals and patent expirations, were also reviewed. Expenditure projections for 2017 for nonfederal hospitals, clinics, and overall (all sectors) were made based on a combination of quantitative analyses and expert opinion. RESULTS: Total U.S. prescription sales in the 2016 calendar year were $448.2 billion, a 5.8% increase compared with 2015. More than half of the increase resulted from price hikes of existing drugs. Adalimumab was the top drug overall in 2016 expenditures ($13.6 billion); in clinics and nonfederal hospitals, infliximab was the top drug. Prescription expenditures in clinics and nonfederal hospitals totaled $63.7 billion (an 11.9% increase from 2015) and $34.5 billion (a 3.3% increase from 2015), respectively. In nonfederal hospitals and clinics, growth in spending was driven primarily by price increases of existing drugs and increased volume, respectively. CONCLUSION: We project a 6.0-8.0% increase in total drug expenditures across all settings, an 11.0-13.0% increase in clinics, and a 3.0-5.0% increase in hospital drug spending in 2017. Health-system pharmacy leaders should carefully examine their own local drug utilization patterns to determine their own organization's anticipated spending in 2017.

National trends in prescription drug expenditures and projections for 2016.

PURPOSE: Historical trends and factors likely to influence future pharmaceutical expenditures are discussed, and projections are made for drug spending in 2016 in nonfederal hospitals, clinics, and overall (all sectors). METHODS: Drug expenditure data through calendar year 2015 were obtained from the IMS Health National Sales Perspectives database and analyzed. Other factors that may influence drug spending in hospitals and clinics in 2016, including new drug approvals and patent expirations, were also reviewed. Expenditure projections for 2016 were based on a combination of quantitative analyses and expert opinion. RESULTS: Total U.S. prescription sales in the 2015 calendar year were $419.4 billion, which was 11.7% higher than sales in 2014. Prescription expenditures in clinics and nonfederal hospitals totaled $56.7 billion (a 15.9% increase) and $33.6 billion (a 10.7% increase), respectively, in 2015. In nonfederal hospitals, growth in spending was driven primarily by increased prices for existing drugs. The hepatitis C combination drug ledipasvir-sofosbuvir was the top drug overall in terms of 2015 expenditures ($14.3 billion); in both clinics and nonfederal hospitals, infliximab was the top drug. Individual drugs with the greatest increases in expenditures in 2015 were specialty agents and older generics; these agents are likely to continue to influence total spending in 2016. CONCLUSION: We project an 11-13% increase in total drug expenditures overall in 2016, with a 15-17% increase in clinic spending and a 10-12% increase in hospital spending. Health-system pharmacy leaders should carefully examine local drug utilization patterns in projecting their own organization's drug spending in 2016.

Considerations in the early development of biosimilar products.

The widespread use and patent expiration of many biologics have led to global interest in development of biosimilar products. Because the manufacture of biologics, including biosimilars, is a complex process involving living systems, the development of a biosimilar is more rigorous than the development of a generic small molecule drug. Several regulatory agencies have established or are proposing guidelines that recommend a stepwise process to ensure the efficacy and safety of a biosimilar are highly similar to the reference product. This article also explores the early clinical phase of biosimilar development, which is particularly important to resolving any uncertainties that might remain following in vitro and in vivo evaluations and to enable a selective and targeted approach to Phase III clinical efficacy and safety investigation.

National trends in prescription drug expenditures and projections for 2015.

PURPOSE: An analysis of trends in U.S. pharmaceutical spending is presented, including projections for drug expenditures in nonfederal hospital and clinic settings in 2015. METHODS: Prescription drug expenditure data through September 2014 were obtained from the IMS Health National Sales Perspectives database and were analyzed descriptively. Other factors that may influence prescription spending in hospitals and clinics in 2015, including new drug approvals and patent expirations, were analyzed. Expenditure projections were based on a combination of quantitative and qualitative analyses and expert opinion. RESULTS: Total prescription sales for the 12 months ending September 30, 2014, were $360.7 billion, 12.2% higher than during the previous 12 months. With $6.6 billion in expenditures in the first 9 months of 2014, sofosbuvir topped the overall list of drugs based on sales, followed by aripiprazole and insulin glargine. Pharmaceutical spending by clinics and nonfederal hospitals rose by 13.3% and 4.0%, respectively. For the first 9 months of 2014, the top drugs based on expenditures were infliximab, pegfilgrastim, and epoetin alfa in clinics and infliximab, rituximab, and pegfilgrastim in hospitals. Specialty drugs continued to constitute an increasing portion of drug expenditures and will contribute to higher expenditures in 2015. CONCLUSION: Growth in U.S. prescription drug expenditures is expected to continue to increase in 2015. The projected increases in total drug expenditures are 7-9% across all settings, 12-14% in clinics, and 5-7% in hospitals. Health-system pharmacy leaders should carefully examine their own local drug utilization patterns to determine their own organization's anticipated spending in 2015.

Accuracy of annual prescription drug expenditure forecasts in AJHP.

PURPOSE: The accuracy of the forecasts of drug expenditures in nonfederal hospitals and clinics published annually in the American Journal of Health-System Pharmacy (AJHP) relative to the accuracy of forecasts produced by the Centers for Medicare and Medicaid Services (CMS) was evaluated. METHODS: AJHP-published forecasts of drug expenditure growth for nonfederal hospitals (for the years 2003 through 2013) and clinics (for the years 2004 through 2013) were compared with data on actual growth. Data on actual and projected growth published by CMS were analyzed for the years 2003 through 2012. The mean absolute error and directional accuracy of the forecasts published in AJHP for nonfederal hospitals and clinics and the CMS forecasts were determined and compared. RESULTS: Actual spending growth was within the range of the forecast published in AJHP for 2 of 11 years for nonfederal hospitals and for 3 of 10 years for clinics; the forecasts for nonfederal hospitals and clinics were directionally accurate 27.3% and 60.0% of the time, respectively. The mean absolute errors of the AJHP-published drug expenditure forecasts for the nonfederal hospital and clinic sectors were 2.0 and 4.7 percentage points, respectively. The CMS forecasts of overall drug spending were directionally accurate 70% of the time, and the mean absolute error (2.2 percentage points) was not statistically different from that of either sector forecast published in AJHP. CONCLUSION: The annual drug expenditure forecasts published in AJHP have been reasonably accurate for predicting growth in prescription expenditures when compared with other available drug expenditure forecasts.

Zoledronic acid: a new parenteral bisphosphonate.

BACKGROUND: Inhibition of bone resorption using bisphosphonates is an important step in palliation of complications of advanced cancer, such as hypercalcemia and metastatic bone disease. OBJECTIVE: The goal of this article was to describe the pharmacologic properties of zoledronic acid (zoledronate) and discuss findings from preclinical and clinical studies of its use in skeletal disorders. METHODS: Relevant English-language literature was identified using the terms zoledronic acid, zoledronate, Zometa, and 118072-93-8 through searches of MEDLINE (1966-June 2003) and International Pharmaceutical Abstracts (1970-June 2003), and abstract proceedings from the American Society of Clinical Oncology (1997-2002). RESULTS: Zoledronic acid is a nitrogen-containing bisphosphonate that inhibits bone resorption. It is indicated for the treatment of hypercalcemia of malignancy and for the treatment of patients with multiple myeloma or documented metastasis from solid tumors, in conjunction with standard antineoplastic therapy. The recommended dosage is 4 mg via IV over >or= 15 minutes every 3 or 4 weeks. Compared with pamidronate 90 mg, zoledronic acid 4 and 8 mg provided a higher complete response rate for hypercalcemia of malignancy by day 10 (88.4% and 86.7% vs 69.7%; P = 0.002 and P = 0.015) and longer duration of action (median time to relapse, 30 and 40 days vs 17 days; P = 0.001 and P = 0.007). In patients with breast cancer or multiple myeloma, zoledronic acid was as effective as pamidronate in delaying time to a first skeletal-related event (373 days vs 363 days). In patients with hormone-refractory prostate cancer and bone metastases, zoledronic acid 4 mg reduced the proportion of patients who experienced a skeletal-related event (33% vs 44% with placebo; P = 0.021) or a skeletal fracture (13% vs 22% with placebo; P = 0.015). In patients with bone metastases from solid tumors, zoledronic acid delayed the median time to a first skeletal-related event (230 days vs 163 days with placebo; P = 0.023). Common adverse events include fever, nausea, constipation, fatigue, and bone pain. CONCLUSION: Zoledronic acid is an effective and generally well-tolerated treatment for hypercalcemia of malignancy and skeletal complications of metastatic bone disease.

National trends in prescription drug expenditures and projections for 2014.

PURPOSE: An analysis of trends in U.S. pharmaceutical spending is presented, including projections for drug expenditures in nonfederal hospital and clinic settings in 2014. METHODS: Trends in pharmaceutical expenditures and developments likely to influence future spending, including new drug approvals and patent expirations, were analyzed using data from the IMS Health National Sales Perspectives database. Projections were based on a combination of quantitative and qualitative analyses and expert opinion. RESULTS: Total prescription sales for the 12 months ending September 2013 were approximately $326 billion, 0.7% lower than sales during the previous 12 months; pharmaceutical spending by clinics and nonfederal hospitals grew by 4.5% and 1.8%, respectively. Vaccines were among the products driving large sales increases in clinic settings, with alteplase and pegfilgrastim topping the list of fast-growing drugs by hospital expenditures. Few new drug approvals anticipated in 2014 are expected to result in major expenditures by hospitals and clinics. Expansion of access to health care and other changes related to the Patient Protection and Affordable Care Act, as well as continued improvement in the U.S. economy, may drive growth in pharmaceutical spending over the next 12-24 months. CONCLUSION: Growth in U.S. prescription drug expenditures is expected to rebound in 2014, with a projected 3-5% increase in total drug expenditures across all settings this year, including a 5-7% increase in clinic spending and a 1-3% increase in hospital spending. Health-system pharmacy leaders should carefully examine local drug-utilization patterns to determine their respective organization's anticipated spending in 2014.

Preliminary report: the development of the NCCN Comparative Therapeutic Index™ as a clinical evaluative process for existing data in oncology.

The National Comprehensive Cancer Network (NCCN) develops and communicates the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to oncologists and other clinicians. The NCCN Guidelines are widely recognized and applied as the standard for clinical policy in the United States. These guidelines and related documents, such as the NCCN Drugs & Biologics Compendium (NCCN Compendium), are used extensively by public and private payors as the basis for the setting of coverage policies. Given the demand for comparative effectiveness (CE) analyses, as described and discussed in this report, the NCCN has begun work on a paradigm to integrate evidence-based CE analysis into the NCCN Guidelines deliberative process. This report presents NCCN's initial thinking on the use of NCCN expert panel members in developing a process that can be used to compare health care technologies (e.g., radiation modalities, chemotherapy regimens) in a formal, systematic way. Draft considerations are provided to stimulate discussion and feedback, particularly in the oncology community, as NCCN moves through processes such as methodologic review, validation of rating scales, and review of implications for public policy, toward finalization of an NCCN CE analytic paradigm.

Insights and perspectives in the clinical and operational management of cancer-related anemia.

Management of anemia in patients with cancer presents challenges from clinical, operational, and economic perspectives. Clinically, anemia in these patients may result from treatment (chemotherapy, radiation therapy, or surgical interventions) or from the malignancy itself. Anemia not only contributes to cancer-related fatigue and other quality of life issues, but also affects prognosis. From the operational perspective, a patient with cancer who is also anemic may consume more laboratory, pharmacy, and clinical resources than other patients with cancer.

Drug-induced QT-interval prolongation: considerations for clinicians.

Drug-induced proarrhythmia is a frequently encountered clinical problem and a leading cause for withdrawal or relabeling of prescription drugs. Suppression of the rapid component of the delayed rectifier potassium current, I(Kr), represents the principal pharmacodynamic mechanism leading to heterogeneous prolongation of the ventricular action potential and prolongation of the QT interval clinically. However, the risk of proarrhythmia by QT-interval-prolonging drugs is variable and critically dependent on several factors leading to multiple reductions in the cardiac repolarization reserve. As antiarrhythmic drugs that prolong the QT interval are usually aggressively managed with continuous electrocardiogram monitoring and screening for drug interactions when administered to patients who have a high risk of sudden cardiac death, their risk of mortality is not increased. However, noncardiovascular QT-interval-prolonging drugs, which often produce less QT-interval prolongation compared with antiarrhythmic drugs, are found to be associated with increased rates of death in patients who have a markedly lower de novo risk of sudden cardiac death. Thus, it is important for clinicians, particularly pharmacists, to be cognizant of the levels of risk associated with varying degrees of QT-interval prolongation caused by drugs so that they can develop strategies to either prevent or reduce the risk of proarrhythmias.

NCCN Task Force Report: Specialty Pharmacy.

The use of specialty pharmacies is expanding in oncology pharmacy practice. Specialty pharmacies provide a channel for distributing drugs that, from the payor perspective, creates economies of scale and streamlines the delivery of expensive drugs. Proposed goals of specialty pharmacy include optimization of pharmaceutical care outcomes through ensuring appropriate medication use and maximizing adherence, and optimization of economic outcomes through avoiding unwarranted drug expenditure. In oncology practice, specialty pharmacies have become a distribution channel for various agents. The use of a specialty pharmacy, and the addition of the pharmacist from the specialty pharmacy to the health care team, may not only provide benefits for care but also present challenges in oncology practice. The NCCN Specialty Pharmacy Task Force met to identify and examine the impact of specialty pharmacy practice on the care of people with cancer, and to provide recommendations regarding issues discussed. This report provides recommendations within the following categories: education and training of specialty pharmacy practitioners who care for individuals with cancer, coordination of care, and patient safety. Areas for further evaluation are also identified.

NCCN Oncology Risk Evaluation and Mitigation Strategies White Paper: Recommendations for Stakeholders.

REMS are a particularly important issue for oncology and the National Comprehensive Cancer Network (NCCN). A disproportionate number of drugs with complex REMS are used in patients with cancer or hematologic disorders. REMS policies and processes within oncology may act as a model for other clinical areas. A breadth of experience and access to a wide knowledge base exists within oncology that will ensure appropriate development and consideration of the practical implications of REMS. NCCN is uniquely positioned to assume a leadership role in this process given its status as the arbiter of high-quality cancer care based on its world-leading institutions and clinicians. Notwithstanding the potential benefits, the successful design, implementation, and analysis of the FDA's recent requirement for REMS for some high-risk drugs and biologics will present significant challenges for stakeholders, including patients, providers, cancer centers, manufacturers, payors, health information technology vendors, and regulatory agencies. To provide guidance to these stakeholders regarding REMS challenges, the NCCN assembled a work group comprised of thought leaders from NCCN Member Institutions and other outside experts. The Work Group identified challenges across the REMS spectrum, including the areas of standardization, development and assessment of REMS programs, medication guides, provider knowledge and impact on prescribing, provider burden and compensation, and incorporation of REMS into clinical practice.