bluuebunny/crossref_metadata_2025_split huggingface dataset:
The master observational trial–a novel method to unify precision oncology data collection.
Authors: Dickson Dane J. , Johnson Jennifer Maria , Bergan Raymond C. , Owens Rebecca , Subbiah Vivek , Kurzrock Razelle 
Published: May 2020

e19313 Background: The Master Observational Trial (MOT) was recently created as a new master protocol that hybridizes the power of master interventional trials with the richness of real-world data (Cell, 2020). The MOT can be described as a series of prospective observational studies that are tied together through a common protocol, infrastructure, and organization. The MOT has broad application in many disease states but is particularly powerful in oncology. We herein expand our prior work to describe key details regarding how the MOT concept can fill multiple unmet needs in oncology. Methods: Through published information, white papers, and expert opinions we identified key unmet needs of oncology stakeholders. We reviewed the publicly available information of structure, organization, and data availability of the five largest genomic-outcome real-world data efforts. Common concerns included variability and reliability of biomarkers, the scientific rigor in real-world data, data silos, patient consent, and duplicated or disparate activities. We then determined how a specific application of the MOT in oncology could answer stakeholder concerns, integrate with current efforts, and also how to provide a model that would be equally valuable to academic and community clinics. Results: We identified significant scientific challenges with many of the current oncology real-world datasets in answering key concerns of stakeholders. We developed the Master Registry of Oncology Outcomes Associated with Testing and Treatment (ROOT) as the first national implementation of an oncology-centric MOT. We modeled how ROOT could fill scientific gaps in current data efforts and integrate with interventional and real-world efforts and help answer key concerns of stakeholders. We also identified solutions that would allow community and academic groups to participate in the same effort. Conclusions: An oncology-centric MOT has the potential to improve the quality of RWD in oncology and advance precision oncology in ways that are not fully addressed by current retrospective efforts. Reference Dickson DJ, Johnson J, Owens R, Bergan R, Subbiah V, Kurzrock R. (2020). The Master Observational Trial: A New Class of Master Protocol to Advance Precision Medicine. Cell 180, 9-14. Clinical trial information: NCT04028479 .
MSI/MMR test usage and checkpoint inhibitor practices in Europe.
Authors: Smith Bradley , Hodge Jeffrey , Anger Caroline , Manuguid Fil , Jindal Kriti 
Published: May 2020

e19327 Background: Micro-Satellite Instability (MSI) or DNA Mismatch Repair (MMR) is an established prognostic test associated with response to chemotherapies in Lynch Syndrome, colorectal cancer and other indications. Recently, MSI/MMR status has been shown to predict response to immune checkpoint inhibitors (CPI). Pembrolizumab has been approved in the USA for MSI-high or mismatch repair deficient patients for all indications. A similar approval has not been obtained in the EU. This data research project examined MSI/MMR testing in Europe and its possible association with use of CPI therapies. Methods: This study was conducted using Oncology Dynamics, an IQVIA oncology cross-sectional survey, collecting anonymized real-world patient-level data. 97,807 and 96,111 drug treated patients for solid tumors in 2018 & 2019, respectively, were collected across 5 European countries (France, Germany, Great Britain, Italy and Spain). Data included number of patients tested for MSI/MMR, results of the test, site and funding type, and the drug(s) prescribed. Results: European MSI/MMR test rates ranged from 3% in Italy in 2018 to 12% in France in 2019. Testing rates increased modestly in all countries over the period. Testing rates were determined in 25 specific indications plus all other indications. As expected, rates were highest in colorectal and stomach cancer. Testing was observed in other indications including Esophageal, Brain and Melanoma all with rates of 10% or higher. The percentage of MSI-High patients ranged from a low of 13% in Italy in 2019 to 26% in France in 2019. Finally, 17% of MSI-High patients are treated with CPIs compared to 5% of MSI-Low patients across all countries in 2019. Conclusions: The results over two years and almost 200,000 patients present insights into the use of MSI testing in 5 European countries. MSI testing is performed in many indications in addition to those typically associated with the biomarker. The increase in CPI use in MSI-High patients suggest that test results may impact use of checkpoint inhibitors although causation may not be inferred from the current analysis. However, the correlation suggests that further analysis is warranted.
Time from diagnosis to 1st line immunotherapy (IOT) and its challenges, in a retrospective, multicenter study of Israeli patients (pts) with advanced non-small cell lung cancer (NSCLC).
Authors: Shimony Udi , Hasid Lior , Deutsch Irad , Malki Eliran , Vorobiof Daniel A. 
Published: May 2020

e19346 Background: The importance of timely treatment of advanced NSCLC and timeline measurements have been the subject of reported studies. Real world evidence data (RWED) via EHR and cutting-edge technology paired with Belong.life pts engagement platform, was evaluated in Israeli pts with NSCLC, members of Belong.life community. Timelines from diagnosis to start of IOT were analyzed by data scientists using AI and machine learning engines. Methods: 30 Israeli pts with advanced NSCLC, members of Belong.life, the largest global social media platform for cancer pts and caregivers, were screened during 2016-8. Demographics, time of diagnosis, time of starting IOT and reasons for treatment delays were documented. Results: 18 pts (60%) were males and 88% had Stage 4. Most pts (87%) were diagnosed during 2017-8. 46 % were < 60 yrs and 54% > 61 yrs. 18 (60%) pts received only pembrolizumab while 11 (37%) pts had it in combination with various chemotherapy drugs. 1 pt received single agent nivolumab. According to the dates reported by 22 (76%) pts, the median time from diagnosis to IOT initiation was 37 days( < 20-96) with 13(59%) starting the treatment in < 40 days. Most common delay causes were due to waiting for genetic tests to define targeted therapy (38%), protracted diagnostic phase (38%) and bureaucratic issues in 27%. Study limitations included its retrospective nature, a convenience sampling, and partial reliance on pts recall of dates. Conclusions: Healthcare systems are seeing an increase in the incidence of most cancers. We report marked variability in time to initiation of 1st LOT therapy of Israeli pts with advanced NSCLC. The common reasons for the delays were obtaining the molecular tests results in order to define targeted drugs and as more targets and their therapies become available this period might increase. Treatment delays are likely to have a negative impact on pts well-being, quality of life and long-term prognosis. Speeding up diagnosis and treatment planning process could decrease pts waiting time, improve their quality of life and expectancy, therefore consideration to the development of a time to treatment protocol should be prioritized.
Blockchain-authenticated sharing of cancer patient genomic and clinical outcomes data.
Authors: Burns Shohei , Collisson Eric Andrew 
Published: May 2020

e19358 Background: Efficiently sharing health data produced during standard care could dramatically accelerate progress in cancer treatments but various barriers make this difficult. Not sharing these data to ensure patient privacy is at the cost of little to no learning from real-world data produced during cancer care. Furthermore, recent research has demonstrated a willingness of cancer patients to share their treatment experiences to fuel research, despite potential risks to privacy. The objective of this study was to design, pilot, and release a decentralized, scalable, efficient, economical, and secure strategy for dissemination of de-identified clinical and genomic data with a focus on late stage cancer. Methods: We created and piloted a blockchain-authenticated system to enable securely sharing de-identified patient data derived from standard of care imaging, genomic testing, and electronic health records (EHR), called the Cancer Gene Trust (CGT). We prospectively consented and collected data for a pilot cohort (n = 18), which we uploaded to CGT. EHR data were extracted from both a hospital cancer registry and a common data model format to identify optimal data extraction and dissemination practices. Specifically, we scored and compared the level of completeness between two EHR data extraction formats against the gold-standard source documentation for patients with available data (n = 17). Results: While the total completeness scores were greater for the registry reports than the common data model, this difference was not statistically significant. We did find that some specific data fields, such as histology site, were better captured using the registry reports, which can be used to improve the continually adapting common data model. In terms of the overall pilot study, we found that CGT enables rapid integration of real-world cancer patient data in a more clinically useful timeframe. We also developed an open-source web application to allow users to seamlessly search, browse, explore, and download CGT data. Conclusions: Our pilot demonstrates the willingness of cancer patients to participate in data sharing and how blockchain-enabled structures can maintain relationships between individual data elements while preserving patient privacy, empowering findings by third party researchers and clinicians. We demonstrate the feasibility of CGT as a framework to share health data trapped in silos to further cancer research. Further studies to optimize data representation, stream, and integrity are required.
Examining the relationship between the clinical benefit of oncology drug indications and the time from pan-Canadian Oncology Drug Review (pCODR) recommendation to public reimbursement.
Authors: Thomson Sasha , Everest Louis , Witzke Noah , Delos Santos Seanthel , Cheung Matthew C. , Chan Kelvin K. 
Published: May 2020

e19360 Background: We examined if publicly reimbursed oncology drug indications with evidence of high clinical benefit, as measured by the American Society of Clinical Oncology Value Framework v2 (ASCO-VF), and European Society for Medical Oncology Magnitude of Clinical Benefit Scale v1.1 (ESMO-MCBS), received reimbursement status faster than those with lower clinical benefit from the time of pCODR recommendation. Methods: Oncology drug indications that received pCODR recommendations between Jan 2012 and July 2018 were identified. Indications that did not receive provincial reimbursement, without notice of compliance, or received a negative pCODR recommendation were excluded. The relationship between clinical benefit, as measured by ASCO-VF and ESMO-MCBS, and the time to reimbursement was evaluated using Spearman correlation coefficient, univariable, and multivariable linear regression analyses. Results: Overall, 84 indications met inclusion criteria yielding 80 ASCO-VF and 66 ESMO-MCBS scores. The mean ASCO-VF and ESMO-MCBS scores were 38.8 (SD = 23.8) and 3.0 (SD = 1.1) respectively. Higher ASCO-VF and ESMO-MCBS scores had low correlation with shorter time to provincial funding, (rho = -0.15, 95%CI -0.24, -0.06) and (rho = -0.25, 95%CI -0.34, -0.16) respectively. Univariable analyses showed that manufacturer reported incremental cost effectiveness ratio (ICER) values, year of pCODR recommendation, province and cancer type were associated with time to public reimbursement (all p < 0.0001). After adjusting for potential confounders in the respective multivariable analysis, ASCO-VF (p = 0.29) and ESMO-MCBS (p = 0.15) scores were not significantly associated with time to public reimbursement. Year of pCODR recommendation remained associated with time to public reimbursement (p < 0.001). Earlier years (2012-2014) had a shorter time to reimbursement (mean = 10.4 months) than later years (2015-2018) (mean = 14.5 months). Other factors that were associated with time to reimbursement in multivariable analysis were province (p < 0.001) and cancer type (p < 0.001). Conclusions: Currently, oncology drug indication with evidence of high clinical benefit do not appear to be funded faster than those with low clinical benefit. This suggests the need to prioritize cancer drug indications based on clinical benefit in order to allow for timely public reimbursement of cancer drugs with higher clinical benefit to patients.
Cost savings of biosimilar pegfilgrastim in a Medicare OCM population.
Authors: Webster Jennifer , Smith Robert E. , Wieland Danielle , Verniero John , Scott Jeffrey A. 
Published: May 2020

e19362 Background: Pegfilgrastim is a key supportive care agent in oncology patients, providing significant febrile neutropenia prophylaxis for patients on chemotherapy. However, pegfilgrastim also accounts for 5.3% of the total cost of cancer care for all patients in the Oncology Care Model (OCM). Fluctuations in the cost or quantity of pegfilgrastim can have significant impact on a practice’s performance under OCM. One such cost fluctuation is the introduction of biosimilars to the marketplace. This study seeks to understand how CMS reimbursement for pegfilgrastim has been impacted by the introduction of two pegfilgrastim biosimilars into the market. Methods: We tracked average CMS reimbursement for pegfilgrastim (Neulasta, Udenyca and Fulphila) from 7/1/2016 through 6/30/2019. We compared the average reimbursement and the average change in reimbursement before and after the introduction of biosimilars. Results: Prior to the introduction of biosimilars, the Medicare Part B reimbursement (80% of ASP +6%) of pegfilgrastim increased at a steady rate of $292 per year through the first 30 months of the OCM program, resulting in an average reimbursement of $3636 per administration in Q3 2018. However, since the introduction of biosimilars, average pegfilgrastim reimbursement has held steady, averaging $3543 for the time period from 7/1/2018 through 6/30/2019. The change in reimbursement has decreased from $292/year to -$93/year. Conclusions: In 2018, 88,847 Medicare patients received pegfilgrastim, resulting in $1.39 billion in Medicare reimbursement. Assuming that the patterns we’ve detected in our OCM data sample can be applied to the general Medicare population, we have estimated that the introduction of biosimilars resulted in a $4.8 million in savings (1.39%) compared with what the total reimbursement would have been without biosimilars in the market in Q4 2018. This bending of the cost curve is projected to result in savings of $79.1M (5.7%) in 2019 and $157.9M (11.5%) in 2020. Importantly, most of this cost containment is not due to patients utilizing biosimilars. 90.6% of patients in Q2 2019 are still receiving branded pegfilgrastim. However, the introduction of biosimilars has caused even the branded agent to stabilize and possibly even drop net acquisition cost prices. Introduction of biosimilars has created enough pressure on the market to result in significant cost savings, increasing the overall value proposition of pegfilgrastim. This results in significant cost saving to CMS, and also makes it easier for practices participating in OCM to have successful financial outcomes.
Financial toxicity in patients with multiple myeloma participating in clinical trials: A U.S. Food and Drug Administration pooled analysis.
Authors: King-Kallimanis Bellinda , Chen Ting-Yu , Kanapuru Bindu , Bhatnagar Vishal , Kluetz Paul Gustav 
Published: May 2020

e19370 Background: Financial toxicity (FT) is a major concern for patients receiving standard cancer treatment, and FT can lead to worse cancer outcomes. However, little is known about the FT of patients enrolled in clinical trials (CT). While investigational treatment may be provided by sponsors free of charge, patients are subject to increased clinic visits (ie, missed workdays, travel costs) and still bear the cost of usual care. This analysis evaluates patient-reported FT in multiple myeloma (MM) trials submitted to US FDA and explores the relationship between baseline FT and overall response rate (ORR). Methods: We pooled data from 9 MM registration CTs submitted to the FDA that included the EORTC Quality of Life questionnaire (QLQ-C30). The QLQ-C30 includes an item asking patients “Has your physical condition or medical treatment caused you financial difficulties?”. We looked at proportion of patients at baseline reporting any FT and their ORR. We also report prevalence, incidence and change from baseline FT at 3 and 6 months. Results: 5,667 patients answered the FT item. Mean age of patients was 65 years, 55% were male, 85% were white and 6% were enrolled in the US. Approximately a third of patients reported experiencing any FT at baseline, 3 and 6 months. When compared to their baseline, 69% of patients had unchanged FT and 14% had worse FT at both 3 and 6 months. The incidence of new cases of FT at 3 months was 17% and at 6 months 7%. The ORR in patients who reported any FT at baseline was 69% compared to 72% in patients with no baseline FT, and was similar regardless of the degree of FT. Conclusions: Few studies have investigated FT in a large sample of CT participants. In this pooled analysis of patients enrolled in MM CTs, approximately a third of patients reported FT associated with their physical condition or medical treatment at baseline and throughout the trial. A small percentage of patients experienced worsening FT during the trial and a small percentage went from no FT to reporting any FT. The impact of baseline FT on ORR was small. Limitations of this preliminary analysis include missing patient level or group level insurance status, socio-economic status and other important determinants of health.
Do we consider to apply the value framework of cancer drugs to clinical practice and health insurance coverage in Korea?
Authors: Kim Do Yeun , Ha Hyerim , Lee Hee Yeon , Koo Dong-Hoe , Han Hye Sook , KIM Hee JUN , Oh Sung Yong , Bae SeungJin , Bae Green , Cho Jae-Young , Kang Jin-Hyoung 
Published: May 2020

e19391 Background: Emerging oncology drugs such as targeted agents and immune checkpoint inhibitors (ICIs) have brought dramatic advances in cancer treatment, while rapid rise in the drug cost. In Korea, the policy of expansion of health insurance coverage has improved accessibility to high-priced oncology drugs through their registrations in reimbursement list. However, this made a considerable impact on the financial burden of national health insurance. The objective of this study was to assess the awareness and perceptions of medical oncologists about the value frameworks of cancer drugs in Korea. Methods: We collected the data from survey for 102 medical oncologists at cancer conference. They were asked about prioritization among multiple considerations when they prescribe cancer drugs, The second question was awareness of value frameworks such as American Society of Clinical Oncology (ASCO) value framework and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Additionally, potential application of value framework to the decision on reimbursement coverage was included. Results: The majority of respondents (90%) chose clinical efficacy as the most important factor when they selected oncology drug for cancer patients. Safety/tolerability and drug cost were followed as 5.9% and 1%, respectively. Meanwhile, the order of priority of considerations for ICIs treatment was as follows: clinical efficacy (74.5%), drug costs (13.7%), and safety/tolerability (9%). More than half of those questioned (53.9%) were already aware of ASCO value framework and ESMO-MCBS, while 26.5% did not recognize them at all. Over 90% of respondents agreed with the need for development of new value framework tool which can be complementary to current valuation system for oncology drugs. Oncologists responded positively to the necessity of the assessment tool as a criterion for reimbursement registration (84.3%) as well as post-reimbursement re-evaluation (89.2%). Conclusions: Our results suggest that value assessment tool of oncology drug be necessary for providing medical evidences for clinical decision and for determination to health insurance reimbursement in Korea.
Assessing the value of cemiplimab for adults with advanced cutaneous squamous cell carcinoma (CSCC): A cost-effectiveness analysis.
Authors: Paul Eleanor , Kuznik Andreas , Keeping Sam , Chen Chieh-I , Sasane Medha , Xu Yingxin , Konidaris Gerasimos , Atsou Kokuvi , Ayers Dieter , Ruiz Emily S , Khushalani Nikhil I. , Cope Shannon 
Published: May 2020

e19397 Background: Cemiplimab is a high-affinity, human, hinge-stabilized, monoclonal antibody that potently blocks the interactions of programmed cell death-1 (PD-1) with programmed cell death ligand-1 (PD-L1) and PD-L2. In September 2018, cemiplimab-rwlc became the first systemic therapy approved by the US Food and Drug Administration for the treatment of patients with advanced CSCC ineligible for curative surgery or radiotherapy. In a single-arm Phase II study (NCT02760498), cemiplimab demonstrated substantial antitumor activity, durable responses, and acceptable safety profile in patients with advanced CSCC. The aim of this analysis was to evaluate the cost-effectiveness of cemiplimab in patients with advanced CSCC from a US payer perspective. Methods: A partitioned survival model was developed to assess the cost-effectiveness of cemiplimab versus historical standard of care (SOC). All inputs were identified based on a systematic literature review (SLR), which was supplemented by expert opinion where necessary. The clinical inputs for cemiplimab were based on the individual patient data from the cemiplimab Phase II trial, whereas for SOC, the analysis was based on a pooled analysis of single-arm clinical trials and retrospective studies evaluating chemotherapy and epidermal growth factor receptor inhibitors (cetuximab, erlotinib, and gefitinib) identified via the SLR (6 of the 27 included studies). Overall survival and progression-free survival were extrapolated over a lifetime horizon using parametric functions consistent with guidance from the National Institute for Health and Care Excellence Decision Support Unit. Costs were included for drug acquisition, drug administration, management of adverse events, subsequent therapy, disease management, and terminal care. Unit costs were based on published 2019 US list prices. Results: In the base case, cemiplimab versus SOC resulted in an incremental cost-effectiveness ratio (ICER) of $99,024 per quality adjusted-life year (QALY), where incremental costs and QALYs were $372,425 and 3.76, respectively. At a willingness-to-pay threshold of USD $150,000 per QALY, the probabilistic sensitivity analysis suggests a 91% probability that cemiplimab is cost-effective when compared to SOC. Scenario analyses resulted in ICERs ranging from $90,326 to $147,944. Conclusions: Compared with historical SOC, cemiplimab is a cost-effective use of US payer resources for the treatment of advanced CSCC and is expected to provide value for money.