bluuebunny/crossref_metadata_2025_split huggingface dataset:
The shift in therapies for the treatment of chronic lymphocytic leukemia (CLL) patients in the US Veterans Health Administration (VHA) from 2013-2018.
Authors: Nooruddin Zohra , Le Hannah , McHugh Daniel , Ryan Kellie , Jones Xavier , Obodozie-Ofoegbu Obiageri O , Teng Chengwen , Eaves Alyssa C , Frei Christopher R 
Published: May 2020

e19339 Background: The first novel agent for use in CLL was approved in 2014; however, the extent of novel agent uptake in the VHA is largely unknown. Objective: This study described the pharmacoepidemiology of three novel agents (ibrutinib, idelalisib, venetoclax), and traditional chemotherapies/chemoimmunotherapies (CT/CIT) in the VHA. Methods: This was a retrospective study of 26,879 adults with CLL in the VHA from 10/01/2013 to 5/31/2018. All were followed for at least 6 months. Data were extracted from the VHA electronic health record. Patients came from all 18 Veterans Integrated Service Networks, spanning all 50 states and US territories. Descriptive statistics were used to summarize baseline characteristics, CLL treatments, next therapies, and secondary complications. Results: A total of 3670 patients received at least one of 12 CLL therapies of interest. Patients had a median age of 69 years (47% were 65+ and 26% were 75+), a median age-adjusted Charlson comorbidity score of 6, and 6% had a history of exposure to Agent Orange. Ibrutinib accounted for 89% of the novel agent use. Ibrutinib use across all lines of therapy (LOTs) increased sevenfold over the study period (Table). Venetoclax (42%) and idelalisib (30%) were the most common therapies for the next LOT after ibrutinib. Across all LOTs, traditional CT/CIT use declined steadily over the study period. However, in fiscal year (FY) 2018, there were still 17% of patients receiving CT/CIT. Ibrutinib was the most common therapy for the next LOT in these patients (43–74%). Incidence of diffuse large B cell lymphoma post-index was 2–6 times higher in patients on CT/CIT than those on ibrutinib. Other secondary complications were similar between ibrutinib and CT/CIT. Conclusions: To our knowledge, this is the largest study looking at CLL treatment patterns among VHA patients in the real world. There has been a major shift in the treatment of CLL, with fast adoption of novel agents in the VHA from 2013 to 2018. The impact of this shift on healthcare resource use and cost burden in the VHA will need to be examined. [Table: see text]
Analyzing the outcome of clostridium difficile infection in cancer patients.
Authors: Sahu Kamal Kant , Mishra Ajay , George Susan V , Abraham George , Siddiqui Ahmad Daniyal 
Published: May 2020

e19340 Background: Clostridium difficile infection (CDI) is a considerable health burden, and now identified as the leading cause of acquired diarrhea in patients receiving antibiotics. Cancer patients are more prone to acquire CDI, owing to their frequent exposure to risk factors. This study aims to investigate the factors affecting the outcome of Clostridium Difficile Infection in patients with cancer at our community center. Methods: This is a retrospective study that included a total of 59 cancer patients who were hospitalized for clostridium difficile infection. Results: The median age of the study population was 79 years with 39 males and 20 females. The patients were suffering from cancer located at the following sites: Prostate (25), lung (19), colon (7), bladder (4), breast (3) and renal (1). There were 52 cases of 1st and 7 cases of recurrent CDI admissions. 40 patients detected to have CDI at presentation while 19 patients developed CDI during hospitalization. CDI categories were as follows: Non-severe (29), severe (28), and very severe (3). There were 33 and 20 patients on chemotherapy and radiotherapy respectively. 27 patients had a recent history of cancer care-related procedures or interventions. 29 patients were from either rehab or nursing facility. There were 39 recent hospitalizations with 29 patients receiving antibiotics. Almost half of the patients were on PPI (29) and 12 were on steroids (20.3%) at the time of developing CDI. Patients with a high-risk qSOFA Score of 2 or more (p-value = 0.008) or a high white blood cell count of > 15 X 109/L (p-value = 0.016) were found to have higher in-hospital mortality. Critical care data suggested that 9 patients required intensive care, 7 patients required vasopressor support, and 6 needed mechanical ventilation. Patients were treated with either vancomycin alone (13), or metronidazole alone (25), or combination therapy with vancomycin + metronidazole (21). The median duration of hospital stay was 6 days with 11 fatalities (18.64%). Conclusions: CDI causes significant morbidity in cancer patients. Factors like high qSOFA score and leukocytosis can help to prioritize and intensify the care and in prognosticating the patients.
Hematologic neoplasms incidence categorised by WHO classification and centralization of treatment facilities in Japan: Analysing a nationwide Hospital-Based Cancer Registry data.
Authors: Okuyama Ayako , Tsukada Yoichiro , Izutsu Koji , Higashi Takahiro 
Published: May 2020

e19348 Background: More than 55,000 patients are diagnosed as hematologic neoplasms in Japan. In this study incidence of hematologic neoplasms was categorised based on the World Health Organisation (WHO) classification, and centralisation of treatment facilities was analysed, using the nationwide Hospital-Based Cancer Registries (HBCR) which covers more than 65% of new cancer patients. Methods: The HBCR data for patients diagnosed in 2017 was used. We categorized patients in line with the 2017 Revision of WHO classification of lymphoid, myeloid neoplasms, and acute leukaemia. Incidence and age distribution was analysed by subtype. Centralisation of treatment facilities for haematological malignancy patients was also analysed. Hospitals were classified into four approximately equal groups based on patient volume per year (very high: over 108 patients; high: 43-107; low: 10-42; and very low: under 10). Results: In total, 51,936 patients in 809 hospitals were identified. Overall average age was 68.4 years (SD 16.5). 43.6% were diagnosed as mature B-cell neoplasms except plasma cell neoplasms, followed by 12.6% of myelodysplastic/myeloproliferative neoplasms and myelodysplastic syndromes, 10.1% of plasma cell neoplasms, 9.4% of myeloproliferative neoplasms, and 8.8% of acute myeloid leukaemia and related precursor neoplasms. 1,438 patients (2.8%) were diagnosed as precursor lymphoid neoplasms and 54.7% of these patients were under 10 years old. Looking at the age distribution of mature B-cell neoplasms, 70s were accounted for 32.6% and 60s were accounted for 26.4%. Among hematologic patients aged 70s, 46.4% were mature B-cell neoplasms and remaining 14.3% of myelodysplastic/myeloproliferative neoplasms. Most of patients received treatment at very high (62.1%, 206 hospitals) or high patient volume hospitals (28.5%, 200 hospitals). Only 1.8% of patients received treatment at very low patient volume hospitals (221 hospitals) which have less than 10 hematologic patients per year. Most of patients received treatment at very low patient volume hospitals were mature B-cell neoplasms. Conclusions: In this study, the first detailed analysis of the number of hematologic neoplasms by subtype was performed. Treatment facilities for hematologic neoplasms patients was almost centralised.
The value of immunotherapy: Comparison of annual cost per patient receiving immunotherapy versus chemotherapy in patients with non-small cell lung cancer.
Authors: Vasekar Monali K. , Agbese Edeanya , Leslie Doug 
Published: May 2020

e19364 Background: Checkpoint Inhibitors (CPI) has revolutionized cancer treatment but financial toxicity can be incurred due to high cost. We performed a population-based analysis examining the cost of CPI vs. conventional chemotherapy (CT) in patients with NSCLC to capture the real-world value of CPI on an individual and community level. Methods: Population based claims database of privately insured individuals, MarketScan was interrogated. Pts in years 2015 and 2016 with ICD 9 or 10 diagnosis of lung cancer who were continuously enrolled in insurance plan for at least 12 months were included. CPT codes for CPIs and CT were used. Outcome Measure was Health Service Use ( surrogate for treatment related toxicity) such as Inpatient Admissions and Emergency Department Use. Cost Categories (US Dollars) noted were Total Costs,Total Out-of-Pocket Costs,Total Outpatient Infusion Costs, Outpatient Infusion Out-of-Pocket Costs, Inpatient Admissions Costs and Emergency Department Use Costs.Statistical tests “paired t tests” and “unpaired t tests” were used to compare the above variables using SAS software. Results: In 2015 of 22,193 with lung cancer 554 received CPI vs CT in 21,639. In 2016 of 22,810 pts 2478 received CPI vs CT in 20,332. Data for CPI vs. CT in years 2015 (a) and 2016 ( b) respectively. p value for each pair was <0.0001 unless as noted below 1. Mean Total Cost: a) 228504 vs. 140,970 b) 202202 vs. 147801 2. Mean Total Out of Pocket Cost: a) 3381 vs. 3308 p=0.4829 b) 3500 vs. 3343 p=0.0021 3. Mean Total Outpatient Infusion Cost: a) 51158 vs. 18634 b) 60087 vs. 18999 4. Mean Total Out of Pocket Outpatient Infusion Cost: a)159 vs. 282 b) 359 vs. 263 5. Inpatient Admission rate: a) 33.75% vs. 59.40% b) 43% vs. 58% 6. Mean Inpatient Admission Cost: a) 53045 vs 69810 p =0.0025 b) 54124 vs 73903 7. ED Visit rate: a) 38.2% vs. 61.4% b) 50% vs. 61% 8. Mean ED Cost: a) 4117 vs. 5265 p=0.0379 b) 4947 vs. 6025 p=0.0001. Conclusions: Despite the higher individual total cost in pts receiving CPI vs CT; the cost of CPI could potentially be offset at healthcare level by lesser expenditure through lower ED visits and inpatient hospitalization. Though the out of pocket costs/patient was statistically different, the mean numerical difference was small between CPI vs CT. Future prospective trials of CPI should also incorporate costs to individual and healthcare systems in addition to evaluating the impact of CPI on Quality of life vs CT to understand the real “value” of CPI. This novel study can serve as a benchmark for future population based studies.
The impact of clinical trial (CTr) participation on savings performance in the oncology care model (OCM).
Authors: Adelson Kerin B. , Canavan Maureen , Mun Sophia , Gross Cary Philip , Sinanis Naralys , Davidoff Amy J. 
Published: May 2020

e19367 Background: The OCM is a Centers for Medicare and Medicaid Services (CMS) alternative payment model, which seeks to curb costs while improving care for patients receiving systemic cancer therapy. CMS models the expected total cost (spending target) for each 6-month episode using historical, geographic and clinical factors including CTr participation. We evaluated the relationship between CTr participation, actual cost of care and performance in the OCM. Methods: We used claims for OCM episodes attributed to the Yale Cancer Center between July 2016 and July 2018. We stratified episodes by CTr participation and used t-tests and chi-square tests to compare total cost, drug costs (Part B and D) and whether actual episode costs were above or below CMS targets. Analyses were conducted for the total sample, and among the most common cancer types. Results: Among 9,387 OCM episodes (5,270 unique patients), 815 (8.7%) episodes involved a CTr. Among non-CTr patients, the mean Medicare cost per episode ($32,909) was modestly higher than the mean episode spending target ($31,746; p < 0.001), while in the CTr group, the mean Medicare cost per episode ($36,590) was substantially lower than the mean episode spending target ($48,124 p < 0.001). Mean drug cost was lower with CTr vs without ($15,650 vs $19,587, p < 0.001). Drug costs also accounted for a lower percentage of total costs for episodes with CTr vs not (41% vs 57%). CTr episodes were more likely to meet spending targets than non-CTr episodes (66% vs 56%, p < 0.001) overall and in breast, lung, and myeloma cancers, although only statistically significant for lung cancer (76% CTr vs 48% non-CTr, p < 0.001). Mean difference between target and actual costs was greater for episodes with CTr (- $11,534) than for episodes without CTr (+ $1,163) (p < 0.001). Conclusions: On average, episodes with CTr participation had substantially lower costs compared with their spending targets, while non-CTr episodes had slightly higher costs compared with their spending targets. While total cost of care was higher for episodes with CTr (as the CMS model predicts), drug costs were significantly lower. As drugs comprise a large proportion of total cost, lower drug costs in CTr episodes likely contribute to savings. Additional research should explore whether other OCM centers with higher rates of CTr participation are more likely to meet spending targets in value-based payment models.
Simulation modeling of cost-savings from conversion of pegfilgrastim to biosimilar pegfilgrastim-cbqv for the prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN) and expanded access to biosimilar prophylaxis.
Authors: McBride Ali , MacDonald Karen , Abraham Ivo 
Published: May 2020

e19372 Background: Biosimilars have the potential to reduce the cost of prophylaxis of CIN/FN. To demonstrate this, we: 1) conducted a US comparative cost-efficiency analysis of CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv over reference pegfilgrastim without or with on-body injector (PEG/PEG-OBI), 2) modeled budget-neutral expanded access to biosimilar pegfilgrastim-cbqv from cost-savings achieved from conversion from PEG/PEG-OBI, and 3) estimated the number-needed-to-convert (NNC) to biosimilar pegfilgrastim-cbqv from PEG/PEG-OBI to purchase one additional treatment of biosimilar pegfilgrastim-cbqv. Methods: Simulation modeling from the US payer perspective utilizing: average selling price (ASP) derived from CMS Q1 2020 reimbursement limits for PEG/PEG-OBI and pegfilgrastim-cbqv;between one and six cycles of prophylaxis in a panel of 20,000 cancer patients at risk for CIN/FN; and conversion rates from PEG/PEG-OBI to biosimilar pegfilgrastim-cbqv ranging from 10% to 100% in this panel. Results: Using current ASP, cost-savings per patient of biosimilar pegfilgrastim-cbqv over PEG/PEG-OBI ranged from $223 (for 1 cycle) to $1,335 (6 cycles). In a panel of 20,000 cancer patients, the savings range from $445,163 (for one cycle of prophylaxis at 10% conversion) to $26,709,788 (6 cycles at 100% conversion). In a single cycle of chemotherapy, these savings translate into expanded access to prophylaxis with biosimilar pegfilgrastim-cbqv ranging from 115 doses at 10% conversion from PEG/PEG-OBI to 1,154 doses at 100% conversion. The savings over six cycles of chemotherapy could provide between 692 additional doses of biosimilar pegfilgrastim-cbqv prophylaxis (at 10% conversion) to 6,921 doses (at 100% conversion). The NNC from PEG/PEG-OBI to purchase one additional dose of biosimilar pegfilgrastim-cbqv is 18. Conclusions: These models demonstrate that CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv can generate significant cost savings that could be reallocated on a budget-neutral basis to provide more patients and/or more cycles with CIN/FN prophylaxis.
Successful transition from bortezomib subcutaneous to generic intravenous bortezomib: Cost savings initiative with global economic impact.
Authors: Shah Bhavesh , Jhaveri Radhika , Sanchorawala Vaishali , Lerner Adam , Sloan John Mark , Sarosiek Shayna 
Published: May 2020

e19375 Background: It is estimated that the U.S. will spend $370 billion in 2019 on pharmaceuticals and by 2020 the cost of cancer care will be approximately 158 billion. Cost containment strategies for high cost drugs are needed. There exists an opportunity to decrease overall cost related to bortezomib by switching patients to generic bortezomib. Generic bortezomib was first approved by the FDA in January 2018 but it can only be administered intravenously. Based on previous studies on occurrence of peripheral neuropathy we hypothesized that patients who have not developed bortezomib induced peripheral neuropathy (BIPN) after or during 4 cycles of subcutaneous (subQ) bortezomib could be switched to IV bortezomib without greatly increasing neuropathy. Methods: A protocol was implemented to switch patients from SubQ to IV bortezomib at our hematology outpatient clinic. Patients had to complete 4 cycles of SubQ bortezomib and have either Grade 1 or no BIPN to qualify to switch to IV bortezomib generic formulation. After approval from the hematology/oncology providers and nursing department, this protocol was implemented to start accrual in November 2018. After provider approval for eligible patients, pharmacists would update the treatment plan orders and also notify nursing and patients of the change. Results: Fifteen patients have received at least 1 cycle of IV generic bortezomib for various indications from Nov 2018 to Nov 2019, ranging from 1 cycle to 12 cycles. The diseases for which bortezomib was being used included multiple myeloma (n = 8) and AL amyloidosis (n = 2), renal transplant rejection and thrombotic thrombocytopenic purpura (TTP). Two of the 15 patients had Grade 1 BIPN prior to switching, while all others reported no neuropathy prior to the switch. None of the patients have developed new neuropathy after making the switch from subQ to IV bortezomib. Nursing and patient satisfaction surveys showed that majority of both groups did not have a preference for IV versus subQ administration. Conclusions: We describe a method to switch from subcutaneous bortezomib to generic IV bortezomib instituted at a large academic medical center as a cost containment strategy. This has resulted in no new cases of neuropathy in our growing data set.
Economic evaluation of the oncotype DX test for hormone receptor positive (HR+) early-stage breast cancer (BC) from the Brazilian societal perspective.
Authors: Mattar Andre , Fonseca Guilherme Ribeiro , Romão Murilo Barato Agudo , Shida Jorge Yoshinori , Jakubowski Debbie M , Chao Calvin Y. , Oliveira Sergio C , Gebrim Luiz Henrique 
Published: May 2020

e19380 Background: Selecting appropriate patients for AC (adjuvant chemotherapy) remains an important issue in BC treatment. Although AC improves clinical outcomes toxicity and economic burden is substantial. The Oncotype DX test identifies high-risk patients likely to benefit from AC who otherwise might not be identified through standard parameters (SP), and low-risk patients unlikely to benefit from AC, avoiding toxicities and inherent risks. This study estimated the incremental cost-effectiveness ratio and budget impact (BI) of Oncotype DX testing from the perspective of the Brazilian Public Health System. Methods: A Markov transitional state model was developed with 3 states: recurrence free, distant recurrence, and death. The model compared the scenario in which patients are screened by SP with a proposed scenario with Oncotype DX testing. Changes in therapeutic recommendations and cost of treatment were obtained from a prospective clinical survey at Pérola Byington Hospital. Additional data was obtained from literature. As a societal perspective analysis, medical costs (test, AC, and adverse events), costs of productivity loss, transportation and employment leave were considered. Population was estimated from BC incidence, proportion of early stage cases, and HR expression. An incremental proportion of 10% per year of patients using Oncotype DX testing was assumed. BI analysis had a 5-year horizon and cost-effectiveness a lifetime horizon (5% annual discount). Results: Oncotype DX results as identifier of a subgroup at higher risk of relapse and greater benefit with AC was dominant over SP. Oncotype DX testing resulted in clinical benefits in terms of life-years gained (0.62) and quality-adjusted life years (0.54), related to lower incidence of distant recurrence and use of AC, both of which greatly impacted quality of life. Testing resulted in economic benefits, with lower average cost per patient (−BRL 3,855). Incorporation of Oncotype DX testing resulted in potential savings reaching BRL 107 million in the 5th year stemming from the decrease in AC and consequent decrease in indirect costs. Conclusions: Patients with HR+, HER2− early stage BC may present different risks of relapse and likelihoods of benefiting from AC. With high clinical impact for patients and high economic impact for the health system, a tool that safely and accurately identifies the subgroup of patients who really needs AC is essential. Oncotype DX test incorporation in the Brazilian Public Health System should be considered.
Cost effectiveness of combination ipilimumab-nivolumab in advanced non-small-cell lung cancer.
Authors: Courtney Patrick T , Yip Anthony T , Cherry Daniel R , Salans Mia A , Kumar Abhishek , Murphy James Don 
Published: May 2020

e19387 Background: The combination of nivolumab and ipilimumab was found to improve overall survival compared to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) in the Checkmate 227 trial. However, nivolumab and ipilimumab are significantly more expensive than chemotherapy, and given the high incidence of advanced lung cancer, incorporating dual checkpoint inhibitors into the standard of care could have substantial economic consequences. In this study, we evaluated the cost effectiveness of combination ipilimumab and nivolumab for the treatment of advanced NSCLC. Methods: We designed a Markov model simulating the three treatment arms of the Checkmate 227 trial: nivolumab plus ipilimumab, nivolumab monotherapy, and chemotherapy. Transition probabilities, such as disease progression, survival, and treatment toxicities, were derived from trial data. Costs (in 2019 United States dollars) and health utilities were estimated from published literature. Incremental cost-effectiveness ratios (ICERs), expressed as dollar per quality-adjusted life-year (QALY), were calculated, with results less than $100,000/QALY considered cost-effective from a healthcare payer perspective. We assessed model uncertainty with one-way and probabilistic sensitivity analyses. Results: In our base-case model, nivolumab and ipilimumab combination therapy increased overall cost by $227,700 and improved effectiveness by 0.55 QALY compared to chemotherapy, resulting in an ICER of $413,400/QALY. Nivolumab monotherapy increased overall cost by $98,500 and improved effectiveness by 0.05 QALY compared to chemotherapy, resulting in an ICER of $1,885,400/QALY. Our model was most sensitive to both the cost and duration of dual immunotherapy. Combination immunotherapy became cost effective at an ICER under $100,000/QALY if monthly costs of treatment were reduced from $26,586 to $8,844 (a 67% reduction) or if maximum allowed duration of immunotherapy was reduced from 24 to 4 months. The model was not sensitive to assumptions about survival differences between the study arms. Probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of $100,000/QALY, dual immunotherapy was less cost-effective than chemotherapy 99.99% of the time. Conclusions: Combination nivolumab and ipilimumab immunotherapy is not cost-effective at current prices despite increasing overall survival for patients with advanced NSCLC.