bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monthly parts a and b costs by service and line of therapy for FDA-approved/NCCN category 1 treatments for patients with metastatic pancreatic cancer.
Authors: Muldoon L. Daniel , Hirsch Jared , Dieguez Gabriela , Cockrum Paul 
Published: May 2019

e18365 Background: Real-world evidence is lacking regarding costs for FDA-approved/NCCN Category 1 treatments for patients with metastatic pancreatic cancer (m-PANC). We analyzed costs by service in the Medicare fee-for-service (FFS) population by chemotherapy regimen and line of therapy (LOT). Methods: Patients with m-PANC were identified using ICD-9/10 diagnosis codes in the 2013-2017 Medicare 100% Limited Data Set claims, which include all Medicare paid FFS claims, except professional services, for 45 million Medicare FFS beneficiaries. We studied mean monthly costs by service category, regimen, and LOT. Patients in our study had two or more claims with a pancreatic cancer (PANC) diagnosis more than 30 days apart and one or more claims with a secondary malignancy (metastasis) diagnosis on or after the first PANC diagnosis date. We defined index date as the earliest metastasis diagnosis date. We excluded patients with pre-index non-PANC malignancies and those without 6 months pre-index and 3 months (or until death, if earlier) post-index Medicare FFS enrollment. LOTs were assigned based on therapies used. LOTs ended the day before a new chemotherapy began, 28 days after the last chemotherapy (if no new chemotherapy), or upon death. We analyzed the FDA-approved/NCCN Category 1 treatments used most commonly in first line (1L): gemcitabine monotherapy, gemcitabine/nab-paclitaxel, and FOLFIRINOX; and in second or third line (2L, 3L): liposomal irinotecan. Results: Mean monthly Parts A and B (excluding professional) costs for 1L gemcitabine monotherapy were lower than gemcitabine/nab-paclitaxel or FOLFIRINOX ($5,267, $9,116, and $8,046, respectively). Part B drug costs other than chemotherapy were higher for FOLFIRINOX than gemcitabine/nab-paclitaxel or gemcitabine monotherapy ($3,881, $1,155, and $827, respectively). Inpatient services were similar across 1L regimens ($2,721-$3,303). Despite disease progression, mean monthly 2L and 3L costs for liposomal irinotecan were $10,809 and $12,225, respectively. Part B drugs other than chemotherapy ($2,133-$2,509) were comparable to 1L regimens, but inpatient services ($2,306-$2,405) were lower. Conclusions: The mean monthly cost increased by LOT for m-PANC FDA-approved/NCCN category 1 regimens. Interestingly, Part A inpatient costs decreased in 2L and 3L, while Part B drug costs other than chemotherapy were comparable.
Use of a modified Delphi panel to define value of combination therapy in oncology.
Authors: Broder Michael , Patel Harshali , Wessler Zac , Gibbs Sarah , Yermilov Irina , Lemay Jeffrey 
Published: May 2019

e18369 Background: Treatment regimens involving 2+ novel oncologics have improved health outcomes in several tumor types. These regimens have significantly higher costs than single agents and older treatments (e.g., chemotherapies), which are still widely used to treat different cancers. Our goal was to determine if current concepts of “value,” such as those described by ICER and other frameworks, adequately capture the value of combination therapies. Methods: Using a RAND/UCLA modified Delphi panel, 8 experts from various backgrounds were provided with a review of current concepts of value and asked to rate them on measurability, relevance, and necessity to determine a combination therapy’s value from 4 perspectives (patient, physician, payer, society). After the first round of ratings, panelists met in person and discussed areas of disagreement. Ratings were repeated, and results used to quantitatively summarize group opinion on concepts recommended for inclusion in a value definition. Results: In both rating rounds, experts agreed treatment, clinical evidence, and health outcomes as important domains in determining value. Experts disagreed on whether societal/cultural beliefs, disease factors (i.e., rarity of cancer, unmet need, burden of disease), and other elements of value (e.g., insurance value, reduction in uncertainty, treatment affordability) needed to be incorporated into value assessments of combinations. Responses differed by perspective. Concepts on which there was disagreement decreased post-meeting (23% to 9%). Conclusions: Experts agreed that “value” for 2+ novel oncologics would have a similar definition to value for all high cost oncology therapies. Four key research opportunities to characterize the value of combination therapy emerged: societal context and patient preference may affect value assessments but are not widely considered in current models; some important benefits are not recognized by patients and may be missed by traditional value assessments; given typical patient and societal preferences, cancer treatments may be systematically undervalued vis a vis other health conditions; and combination therapies may present challenges for recently promulgated value frameworks.
Role of advanced practice providers (APP) in meeting rising demands on oncology practices.
Authors: Bapat Bela , Smith Yolaine , Klink Andrew , Nabhan Chadi , Feinberg Bruce A. 
Published: May 2019

e18372 Background: The role of advanced practice providers (APPs), nurse practitioners (NPs) and physician assistants (PAs), is expanding in oncology for myriad reasons including improving access to care by closing the gap between demand for services and physician availability. This is especially true in oncology, where the shortage of oncologists and increasingly cited physician burnout is creating challenges for many practices and communities. Methods: We surveyed US physicians to understand their practices’ use of APPs, their role in patient treatment and support as well as their impact on practice workflow. Data were collected using web-based instrument between Sep 2018 and Nov 2018. Responses have been summarized using descriptive statistics. Results: Among 163 oncologists and hematologists surveyed, 74.2% (n = 121) employed NPs, 39.9% (n = 65) employed PAs, and 19.0% (n = 31) did not employ any APPs in their practice. Amongst practices that employed ≥1 APP (n = 132; 81.0%), over 40% of physicians reported a 1:3 APP: physician ratio. Most (62.1%) physicians stated that APPs only evaluated and saw returning patients, whereas 35.6% physicians used APPs to evaluate and see both new and return patients. More than 60% of physicians stated that APPs enhanced their practice efficiency, enabled physicians to focus more on complex patient cases, and made their workload manageable. By employing APPs, 52.3% of physicians were able to increase their patient caseload. The majority (57.6%) of physicians reported that they would employ more APPs in the next 3 years if resources were available, and 41.7% of physicians reported that APPs would likely take on additional responsibility in the next 3 years. Conclusions: Most community oncology practices in the US are employing APPs and are finding significant value in the APP roles by delegating various aspects of patient care to them. Most community practices are considering increasing the number of employed APPs and to expand the breadth of their responsibility. Integrating APPs into oncology practices is likely to have a larger impact on quality of patient care and potential mitigation of physician burnout.
Community oncologists perceptions and readiness to implement Medicare Access and CHIP Reauthorization Act (MACRA).
Authors: Bapat Bela , Smith Yolaine , Klink Andrew , Nabhan Chadi , Feinberg Bruce A. 
Published: May 2019

e18374 Background: The Medicare Access and CHIP Reauthorization Act (MACRA) was introduced in 2015 with the intention of transforming healthcare administration to improve the quality of care and lower its cost. Understanding challenges facing physicians in how to implement MACRA and recognizing their perceptions regarding these challenges are critical steps to the success of this program and future transformation efforts. Methods: In this study, US oncologists attending live meetings were surveyed on their perceptions of MACRA. Data were collected in 2 time periods: period 1 spanned Nov 2016 to Jun 2017 and period 2 spanned Sep 2018 to Nov 2018. Each physician attended a live meeting in each period. Data were collected in period 1 using audience response system technology and web-based surveys; period 2 data were collected using web-based surveys only. We aimed to compare responses between periods 1 and 2 to assess whether perceptions and challenges changed. Results: There were 97 community oncologists and/or hematologists who responded to both periods. Of the responding physicians, 31.2% were participating in the Oncology Care Model program. A greater proportion of physicians expressed some level of confidence in executing MACRA requirements and achieving financial success in period 2 compared to period 1 (74.2% vs 52.4%; P< 0.01). Additionally, more physicians in period 2 reported having the resources and staffing needed to manage changes required by MACRA (24.7% vs 11.4%; P= 0.02). Strategies in place to improve on compliance with MACRA did not significantly change between both periods (34.2% vs. 28.9%; P = 0.45). Confidence that MACRA would improve patient outcomes in the long-term was expressed by 33.0% in period 2, which was significantly higher than in period 1 (17.6%; P= 0.02). However, most physicians in period 1 were not confident that MACRA would reduce cost of care (89.6%), but this improved to 61.9% in period 2 ( P< 0.01). Conclusions: Over time, oncologists seem more confident about their practices’ readiness for implementing MACRA. However, they remain skeptical of MACRA’s likelihood of improving quality or cost of cancer care and appear to need better strategies to assure sustainability.
Acute kidney injury in childhood cancer: An insight from Kids' Inpatient Database.
Authors: Elsabbagh Eman M , Hashmat Shireen 
Published: May 2019

e18379 Background: Oncology patients are at high risk for Acute Kidney Injury (AKI). AKI may occur due to direct injury from primary cancer, nephrotoxic effects of chemotherapy, hematopoietic stem-cell transplantation or following comorbidities like sepsis and metabolic disturbance. AKI is associated with prolonged hospital stay, high healthcare cost and increased mortality in critically ill patients. Despite the increased risk and these associations, the national rate and clinical outcome of AKI among pediatric oncology patients is not well described. Objective: Define AKI incidence and health outcomes among pediatric oncology patients in the United States (U.S.). Methods: We performed a retrospective cohort analysis of the Health Cost and Utilization Project (HCUP) Kids’ Inpatient 2000-2012 Database (KID) for patient ≤ 20 years of age. Patients with principal diagnosis of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), lymphomas (Hodgkin and non-Hodgkin), brain tumor, neuroblastoma, bone tumors (Ewing’s Sarcoma and Osteosarcoma) and hepatoblastoma were reviewed. Encounters for chemotherapy were excluded. Patients with medical diagnosis of AKI were identified using ICD-9-CM codes. We performed descriptive statistics to characterize the cohort in terms of demographic factors (age, race, sex, insurance type), hospital characteristics and comorbidities. Data weights were applied to sampled patients to provide national estimates. The in-hospital mortality rate, total charges, and hospital length of stay (LOS) were compared between cancer patients with and without AKI using bivariable analyses. Results: A total of 266,113 admissions were included for analysis. The cohort was comprised of 4,761 patients with AKI, with an overall incidence 18 per 1,000 admissions. The median age was 13 years. Males (58.45%), and whites (55.4%) were more commonly affected. South and west regions (59%) of the U.S. had higher frequency of AKI. AML was the most common diagnosis associated with AKI (4.1%). Patients with AKI had significantly higher mortality rates (21.78% vs. 1.36%, p < 0.0001), longer median LOS (15 days vs. 4 days, p < 0.0001) and higher median total charges per hospitalization ($132,712 vs $18,856) when compared to patients without AKI. Conclusions: AKI in pediatric oncology patients is significantly associated with increased in-hospital mortality, LOS, and higher healthcare cost in pediatric oncology patients. This area needs focused research and quality improvement initiatives.
Efficacy and cost-effectiveness of HER2+ early breast cancer therapies.
Authors: Fonseca Magalhães Filho Marcos , Aguiar Pedro Nazareth , Haaland Benjamin , Del Giglio Auro , Lopes Gilberto 
Published: May 2019

e18380 Background: Human Epidermal Growth Factor Receptor 2 (HER2) overexpression occurs in up to 25% of breast cancer (BC) cases. Patients with HER2+ tumors have a poor prognosis even when the disease is detected at an early stage with a recurrence rate of 15-19%. The aim of this study is to assess the best approach (pertuzumab plus trastuzumab [T+P], trastuzumab for 12 months [T12], trastuzumab for 6 months [T6], or T-DM1) in terms of evidence-based medicine and cost-effectiveness. Methods: The authors extracted individual patient data and estimated Invasive Disease-Free Survival (IDFS) and Overall Survival (OS) over a 30-years lifetime horizon. We considered only direct costs from adjuvant treatment as well as recurrence treatment from a Brazilian payer perspective. Heart events were considered for utility and cost analysis. After the base case, the authors assessed cost-effectiveness among N+ patients. In the meta-analysis, we included individual patient data for the intention-to-treat (ITT) population and Bayesian comparisons for subgroup analysis (HR+/HR- and N+/N). Results: We included individual patient data from 12,753 patients. The 4-year IDFS rate was 92.9% for T+P, 89.8% for T12 (HR 1.37, 95%CI 1.16-1.63) and 87.1% for T6 (HR 1.73, 95%CI 1.45-2.06). The 4-year OS rate was 96.7% for T+P, 95% for T12 (HR 1.37, 95%CI 1.07-1.75) and 93% for T6 (HR 1.82, 95%CI 1.42-2.34). T+P, T12 and T6 had similar efficacy among patients with HR+ tumors. T+P and T12 were superior to T6 among HR- patients. T+P was superior to T12 and T6 among N+ patients. T+P, T12 and T6 had similar efficacy among N- patients. In the base case, T+P had an ICER of $332,903 compared to T12. T12 had an ICER of $42,774 compared to T6. Among N+ patients, T+P had an ICER of $308,019 compared to T12. Among patients without complete response after neoadjuvant treatment, T-DM1 had an ICER of $3,233 compared to trastuzumab. Conclusions: T+P had a modest benefit in terms of 4-years IDFS and OS, although it was not cost-effective due to its high cost. T12 remained above the cost-effectiveness threshold compared to T6, but further studies are needed in order to define patients for T6. T-DM1 was cost-effective compared to trastuzumabe for patients who did not achieve complete response after neoadjuvant treatment.
Utility of tumor genomic profiling in guiding targeted therapy and referral for clinical trials in the community practice.
Authors: Xu Yiqing , Yio Jiang , Yang Amber , Bayewitz Ashrei , Benasher Daniel , Fu Lung 
Published: May 2019

e18381 Background: Next-generation sequencing (NGS), which enables tumor genomic profiling with limited tumor specimen for the guidance of targeted therapy, has been widely used in oncology practice. It also reports mutations of which no approved therapy is available, but potential therapies approved in a different tumor type may be reasonable to try, based on molecular mechanisms or limited data, either in clinical trials or off trial treatment. The utility of this information in the community practice is unclear. Methods: We performed a retrospective analysis on the usage of NGS result on patients with lung or colorectal cancers treated between November 2011 and February 2018. Patients were identified from Foundation Medicine Company database and were linked to records at Maimonides. We evaluated if NGS was used to guide FDA-approved targeted therapy, potentially-useful targeted therapy not approved for the cancer type, or referral to a clinical trial. Results: 177 patients (lung ca = 119, colon ca = 58) were included. NGS identified 34 (28.6%) lung ca patients with driver mutations, (21 EGFR, 6 RET, 3 ALK, 2 MET amplification, 1 ROS1 and 1NTRK mutation), who were all given FDA-approved therapy. 70 (58.8%) patients had at least 1 target with an FDA-approved therapy for a different cancer; 89 (74.9%) had a mutation being studied in a clinical trial, and 48 patients were eligible for the NCI-MATCH trial. None received non-FDA-approved drugs and none was referred to clinical trials. In the colon cancer cohort, NGS identified alterations in KRAS (27), BRAF (5), ERBB2 mutation (2), ERBB2 amplification (1), MLH1 (1), MSH2 (1) and BRCA 2(1). Among them, one patient received BRAF inhibitors. 45 and 24 patients were eligible for phase I/II trials and NCI-MATCH trial respectively, and none was referred. Conclusions: NGS has a high efficiency of detecting driver mutations in lung cancer; but only reveals low frequencies of alterations otherwise not tested in colon cancer. The approach of prescribing un-approved targeted treatment based on theoretical mechanism of action was very uncommon, and the referral to clinical trials was rare in this community practice, both of which decreasing the utility value of NGS.
Out of pocket costs and financial toxicity experienced by patients in early phase clinical trials.
Authors: Huey Ryan , George Goldy , Phillips Penny , White Revenda , Fu Siqing , Janku Filip , Karp Daniel D. , Naing Aung , Piha-Paul Sarina Anne , Subbiah Vivek , Tsimberidou Apostolia Maria , Pant Shubham , Yap Timothy A , Rodon Ahnert Jordi , Meric-Bernstam Funda , Shih Ya-Chen T. , Hong David S. 
Published: May 2019

e18383 Background: Clinical trials are an important therapeutic option for cancer patients. Although financial burden in cancer treatment is well-described, the financial burden associated with clinical trials is not well understood, especially for patients with lower socioeconomic status. Methods: We conducted a survey regarding economic burden and financial toxicity among cancer patients on Phase I clinical trials for at least 1 month. Financial Toxicity Score (FTS) was assessed using the validated COmprehensive Score for Financial Toxicity (COST) survey (scale 0-44, lower scores indicating worse financial toxicity). Patients also reported monthly out of pocket (OOP) medical and non-medical expenses. Results: Of 147 consecutive patients approached, 105 agreed to participate; median age = 60y; 62% female; 49% had annual income < $60K; 50% lived < 300 miles from the clinic; 34% required air travel; 41% had Medicare, 50% had employer sponsored insurance. Median FTS = 20, with interquartile range of 12.5. Median monthly OOP costs for non-medical expenses was $985, and for medical expenses was $475. Median total monthly OOP costs was $1695. Compared to patients in the highest quartile of FTS, a significantly lower % of patients in the lowest (worst) quartile of FTS had incomes > $60K (27% v. 77%, P < 0.001), and a significantly higher % were unemployed or not working outside the home (54% v. 12%, P = 0.001), and incurred higher than expected medical (39% vs. 12%, P = 0.025) and non-medical (64% vs. 15%, P = 0.003) expenses. Compared with patients for whom medical costs were not much higher than expected, a significantly higher % of patients with medical costs much higher than expected were non-White (77% v. 46%, P = 0.004) and unemployed/not working outside the home (46% v. 19%, P = 0.009). Conclusions: Among cancer patients participating on clinical trials, economic burden is high and financial toxicity is disproportionally higher in patients with lower income. OOP costs can be substantial and are often unexpected for patients.
Value appraisal of FDA approved cancer drugs over the past decade.
Authors: Huey Ryan , Anand Seerat , Rogers Jane , Dasari Arvind , Varadhachary Gauri Rajani , Gothwal Anirudh , Loree Jonathan M. , Ellis Lee M. , Overman Michael J. , Raghav Kanwal Pratap Singh 
Published: May 2019

e18385 Background: Value based drug pricing is emerging as an imperative health care precept in recognition of the ever-increasing drug costs, especially in oncology. Though novel therapies are regularly approved based on benefit, they are often associated with physical and financial toxicities to patients. We aimed to assess the value of FDA approved oncology drugs defined as their expected clinical benefit compared to their toxicities and costs. Methods: We reviewed all new cancer drug approvals by the FDA from 7/2008-6/2018. Current analysis was restricted to approvals based on overall survival (OS) and progression-free survival (PFS). Data regarding approval indication, effect size, and toxicity were collected from FDA website and publications. Toxicity was estimated as adverse events ≥ grade 3 (or serious adverse events) as reported. Micromedex RED BOOK was used to estimate the total drug price using 2018 average wholesale prices. Price was estimated over 3 months to account for difference in drug regimens. Results: Among the 231 trials used by FDA for approvals in oncology, 115 had OS or PFS as their primary endpoint. Median patients per trial was 539. Of 79 trials with a PFS endpoint, the median HR was 0.50 (range: 0.15 - 0.91); median 3-month drug price was $45,903.72. Compared to the control arm, median toxicity for new drugs was 7% higher (range: -34.4 - 55%). Correlation of HR benefit to 3-month price was 0.06 (95% CI: -0.17 - 0.28, P = 0.61). Correlation of net toxicities to 3-month price was 0.01 (95% CI: -0.25 - 0.26, P = 0.94). Of 43 trials with an OS endpoint, the median HR was 0.72 (range: 0.37 - 0.94); median 3-month price was $43,523.46. Relative to control arm, median toxicity for new drugs was 4% higher (range: -34.4 - 45.8%). Correlation of HR benefit to 3-month price was 0.38 (95% CI: 0.08 - 0.62, P = 0.012). Correlation of net toxicities to 3-month price was -0.12 (95% CI: -0.45 - 0.24, P = 0.50). Conclusions: Drug approvals in oncology come with a high cost and drug prices have very little correlation with estimated benefit in outcomes and toxicities. As policies evolve to promote higher value in health care, attention should be paid to benefits of drugs in relation to pricing and using biomarker-based patient selection to maximize benefits and minimize toxicities.