bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prioritizing targeted therapies in an evidence-based manner, integrating biological context and functional precision medicine.
Authors: Boca Simina , Bhuvaneshwar Krithika , Fernandez-Vega Virneliz , Kancherla Jayaram , Rao Shruti , Madhavan Subha , Riggins Rebecca , Beckman Robert A. , Corrada Bravo Hector , Scampavia Louis , Spicer Timothy 
Published: May 2020

e14065 Background: It is becoming increasingly common for cancer patients to undergo molecular profiling of their tumors in order to see whether there are any actionable DNA, gene expression, or protein expression signatures. For example, individuals with ER+ or HER2+ breast cancer or KRAS wild type (non-mutated) colorectal cancer are prescribed specific targeted therapies. When an individual’s molecular alterations do not match any currently-approved recommendations for their tumor type, their clinician may consider prescribing a therapy approved in a different tumor type. Unfortunately, tumors often eventually become resistant to the therapies they are exposed to, leading to a narrowing of options after each therapy line. Methods: We previously developed CDGnet, an evidence-based approach and web-based tool for prioritizing targeted therapies based on tumor molecular profiles based on known pathways which provide biological context. CDGnet considers approved therapies with biomarkers among the alterations for the individual’s tumor type and other tumor types as the first and second evidence level categories respectively. These are followed by therapies that target or have as biomarkers genes or proteins downstream of altered oncogenes, considering curated pathways for the individual’s tumor type and other tumor types as the third and fourth evidence level categories respectively. We are currently expanding CDGnet in order to include data from high-throughput screening (HTS) experiments of NCI oncologic drugs performed on patient-derived organoids. The concept of “functional precision medicine” consists of using functional drug efficacy determination directly on individual patients, in this case by considering drugs with low half maximal effective concentrations (EC50) which are tested on tissues derived from the actual patients. Results: We will present extensions to CDGnet that allow users to upload both the molecular profiles and the HTS data to see whether any drugs are predicted by both approaches or whether specific combinations appear promising for further testing. Preliminary results on a set of glioblastoma samples will be presented. Conclusions: We hope that extending CDGnet to also include HTS data will eventually allow a truly multi-factorial personalized oncology approach, whereby both molecular alterations at the DNA, RNA, and protein levels and patient-derived organoids will be considered in deciding on treatment plans for individuals.
Patient engagement in clinical trial design and implementation: A pragmatic approach to valued insights.
Authors: Aubel Dawn , Hayes Susan , Cook Geoffrey , Salamakha Alexey , Ciupek Andrew , Patel Gunjan , Mason Ginny 
Published: May 2020

e14084 Background: Evidence-based guidance on how to best facilitate patient engagement in the drug development process is lacking1,2.Well-informed, engaged patients and advocates can contribute meaningfully throughout drug development process for new therapeutics3. Regulatory agencies, including the FDA and EMA, concur4,5. However, identifying and effectively implementing meaningful, and structured patient engagements has been challenging for research organizations6. Methods: Patient advocates with deep knowledge of the special needs of patients within their respective disease areas and experience in patient-centered research and programming were identified by the patient relations’ team of the organization. Participating advocates were generally contracted for consulting support across the development lifecycle to provide timely feedback for emerging topics and agreed to provide feedback within a 3-4 week timeframe to requests for support. Called “Global Oncology Patient Insight Panel” (GOPIP), the approach facilitated fast-moving development teams to quickly engage advocates for advice while enabling projects remain on timeline. GOPIP members engaged with teams within the organization on an ad-hoc basis across the drug development process, as early as protocols’ and informed consents’ review and PRO selection, among many others patient-centered projects. Results: GOPIP engagements included 49 advocates from 19 countries, across 14 disease areas, in the program’s first 18 months. 54 projects were completed. Multiple engagements for three clinical trials, part of the development program, have been accomplished. Seven plain language summaries of published data results were reported publicly with consultants’ input. Satisfaction was high among advocates as well as internal teams. Conclusions: The Patient Insight Panel model is a valuable resource to facilitate patient engagement efforts. More research is needed to evaluate the outcomes and effectiveness of the method. References: 1. Chalasani, M., et al. 2018. Res Involv Engagem. 4,10 2. de Wit, M., et al. 2019. The Lancet, 393(10176),1095-1096 3. Kuehn, C. M. 2018. Ther. Innov. Regul. Sci., 52(5),661–668 4. FDA. 2020. https://www.fda.gov/about-fda/oncology-center-excellence/patient-focused-drug-development . Accessed February 8, 2020 5. EMA. 2016. https://www.ema.europa.eu/en/documents/other/appendix-2-guideline-evaluation-anticancer-medicinal-products-man_en.pdf Accessed February 8, 2020 6. Geissler, J., et al. 2017. Ther. Innov. Regul. Sci., 51(5),612-619.
Assessment of ovarian function as an endpoint in breast cancer clinical trials: A systematic review.
Authors: Cui Wanyuan , Francis Prudence A. , Loi Sherene , Hickey Martha , Stern Catharyn , Partridge Ann H. , Loibl Sibylle , Phillips Kelly-Anne 
Published: May 2020

e14098 Background: Premature ovarian failure (POF) is an established adverse effect of chemotherapy for breast cancer (BC); little is known about the ovarian toxicity of newer treatments (e.g. PARPi, CDK4/6 inhibitors, immunotherapy, anti-HER2 therapy). This study examined whether contemporary BC (neo)adjuvant clinical trials will provide data on POF. Methods: Eligible studies were phase 3 (neo)adjuvant trials of pharmacologic agents aimed to reduce BC events, that enrolled premenopausal women between June 2008 - Sept 2019. MEDLINE and EMBASE were searched using MESH terms / keywords: “breast neoplasm” or “breast adj2 (cancer* or tumo?r* or carcinoma*)”, “adjuvant chemotherapy” or “neoadjuvant therapy” or “neoadjuvant” or “adjuvant”. Clinicaltrials.gov and EudraCT were searched using the filters “breast cancer”, “interventional studies”, “phase 3”. Data extracted from eligible trial publications, protocols and clinicaltrials.gov/EudraCT summaries, included whether each trial assessed the variables - post treatment pregnancy/birth, attempt at pregnancy, menstrual data, antral follicle count, FSH, LH, estrogen, progesterone and AMH levels. Results: Of 1665 trials screened, 141 were eligible. Investigational treatments included chemotherapy (71%), endocrine (20%), anti-HER2 (26%), immunotherapy (8%), CDK4/6 inhibitor (5%), PARPi (2%). Few trials (28%) assessed quality of life (QOL). Study chairs were from Nth America (19%), Europe (36%), Asia (43%); most (67%) were male. POF and fertility measures were prespecified endpoints in 9 (6%) and 0 trials respectively. Twenty (14%) trials collected POF and/or fertility data; post treatment pregnancy (11/20), amenorrhoea (6/20), estrogen (8/20), FSH (7/20), LH (5/20), AMH (3/20), and progesterone levels (1/20) and antral follicle count (3/20). Assessment of POF was associated with collection of QOL data (p = 0.02) but not with BC phenotype, timing, treatment type, or sex or nationality of study chair. Conclusions: POF measures are rarely prespecified endpoints and are infrequently collected in phase 3 BC (neo)adjuvant trials. Trialists should consider POF, given the potential for this data to enhance informed decision making for premenopausal patients.
An innovative approach to manage cancer patient information for care coordination and monitoring using a digital health platform for a nonprofit tertiary cancer care institute in India.
Authors: Hensley Alford Sharon , Gupta Rishi Kumar , Sonawane Nayan , Mahatma Srishti , Mahatma Shilpa , Kumar Tarun 
Published: May 2020

e14102 Background: In India, most patients maintain a personal copy of their medical record in paper form which is hard to manage and collate. Newly diagnosed cancer patients and their doctors have an insurmountable task of consuming and using that information. Making this information available in an easy to consume format as well as recording a patient’s cancer experience is a technical challenge. We piloted an innovative mobile application to address this pain point. Methods: A pilot engagement was performed with 100+ cancer patients visiting a non-profit oncology center between March 2019 and January 2020 in a suburb of New Delhi, India. Systematic medical information was captured on stage, TNM, molecular markers, tumor size, tests, and treatments. We assessed the utility of a digital health application for the purpose of cancer information management and ease of use by the medical team. Results: Data for a total of 65 patients with a single cancer and diagnosis and treatment information was captured. Patients were between the ages of 23 and 78, mean age 49. Of these patients, there were 21 (32%) early stage cases ( < Stage 3), 23 (35%) late stage cases ( > Stage 2), and 21 (32%) cases with missing stage. Overall, 39 (60%) received a chemotherapy only regimen, 2 (3%) radiation only, 6 (9%) surgery only, 6 (9%) received chemotherapy and radiation, 11 (17%) received surgery and chemotherapy, and 1 (1%) patient received surgery, chemotherapy, and radiation. Clinic staff reported that the application was easy to use and helpful. We continue to enhance the application with staff feedback. Conclusions: We demonstrate the feasibility and value of moving to a next generation digitized mobile platform circumventing the need for a traditional EMR system at a busy non-profit oncology clinic in the suburbs of New Delhi, India. Using the pilot, we make a case that this type of technology has the ability to transform cancer care for rural and low-resource cancer centers. We also demonstrate that it is easy to capture patient longitudinal data using this innovative platform.
Preferences and motivational factors for the use of digital technology in real world oncology studies.
Authors: Dias Nadeeka , Yamamoto Rinah , Faulkner Kenneth G 
Published: May 2020

e14119 Background: Patient engagement and motivation during real world oncology studies can be challenging. Digital tools have proven to be effective in reducing patient burden and improving data collection and accuracy. Given the rapid advances in health technology, patient preferences and motivations for these tools are continually evolving. This study investigates preferences for digital technology use with smartphones and wearables, telehealth, and identifies motivational factors that would drive real world study compliance for daily symptom reporting. Methods: Patients (n = 50; 68% male) diagnosed with cancer answered questions via an anonymous online survey about their technology preferences. Results: Although the majority of the population uses smartphones (99%), few oncology patients use wearable technology such as a fitness watch (18%). Of those who do not own a fitness watch, 90% were willing to use the technology in a clinical study and share their data if a watch were provided to them. However, the majority of patients (74%) would prefer to use their own smartphone during a clinical study to answer questions and conduct video calls with the study doctor. For patients who currently visit their doctor in person (98%), almost half (48%) would prefer a remote alternative such as a video call for convenience, especially when in pain. Patients reported several factors that would encourage consistent daily reporting of study data. Out of 10 options, the most motivating factor was access to health information that would help manage their symptoms on a daily basis (92%). Subsequent factors of interest included in-app reminders (88%) and assurance that a doctor would review the reported data and contact them to discuss reported symptoms (94%). Conclusions: The global market for digital health is growing rapidly, and there is a strong preference from oncology patients to shift in-person engagement and reporting to digital platforms. Patients are also highly motivated by information about their own health. Designing real world studies to incorporate these preferences may result in enhanced patient engagement, improved compliance, and higher quality data.
FDA’s Oncology Center for Excellence Pilots Project Orbis: A framework for concurrent submission and review of oncology products among international partners.
Authors: Spillman Dianne , Arora Shaily , Venugopal Rajesh , Scott Bradley , Golding Sarah , Richardson Nicholas , Kasamon Yvette L. , Ethier Jean-Francois , Gurd Kate , Singh Harpreet , DeClaro R. Angelo , Beaver Julia A. , Kim Tamy , Goldberg Kirsten B. , Kluetz Paul Gustav , Theoret Marc Robert , Pazdur Richard 
Published: May 2020

e14125 Background: Cancer therapeutics often receive FDA approval months to years before regulatory submission to other countries. [i] Registrational trials in oncology are increasingly international, with many patients enrolled outside of the United States. Harmonizing access to new global standards of treatment may facilitate optimal design and conduct of global clinical trials. Methods: In May 2019, the Oncology Center for Excellence launched Project Orbis in collaboration with the Australian Therapeutic Good Administration (TGA) and Health Canada. The aim of this initiative is to provide a framework for concurrent submission and review of oncology products among international partners to facilitate global access. Results: The first Project Orbis was a collaborative review of a supplemental application for lenvatinib and pembrolizumab for patients with advanced endometrial cancer. This review also deployed other OCE regulatory review tools including the Real-Time Oncology Review (RTOR) pilot program, which can streamline the submission of data prior to the completion and submission of the entire application, and its accompanying Assessment Aid, to facilitate discussions among regulatory agencies. Lenvatinib and pembrolizumab was approved on September 17, 2019, in conjunction with the TGA and Health Canada, three months prior to the FDA goal date. FDA, TGA, and Health Canada issued a second action under Project Orbis on November 21, 2019, with the approval of acalabrutinib for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Several other products are under international review as part of this pilot program and a summary of timelines and outcomes will be described. Conclusions: Project Orbis is an innovative OCE initiative that leverages the Center’s longstanding communication and collaboration with international regulators. This pilot program facilitates concurrent submission and review of oncology products among global regulatory health agencies. Continued efforts under Project Orbis will build on the initial success to incorporate additional global partners including Swissmedic and Singapore’s Health Science Authority. [i] The Centre for Innovation in Regulatory Science (CIRS). R&D Briefing 70 New drug approvals in six major authorities 2009-2018: Focus on Facilitated Regulatory Pathways and Orphan Status
Responding to narrowing discrimination protections: Can hospital policies protect transgender and gender diverse patients with cancer?
Authors: Alpert Ash , Tarras Elizabeth Stieglitz , Sampson Amani , Strawderman Myla S. , Sutter Megan , Quinn Gwendolyn P. 
Published: May 2020

e14126 Background: The U.S. Department of Health and Human Services recently proposed to eliminate federal protections against discrimination in healthcare on the basis of gender identity. This proposal seeks to alter the Patient Protection and Affordable Care Act Section 1557 Rule, which currently prohibits sex discrimination in any health program receiving federal financial assistance. The provisional change poses imminent threats to transgender and gender diverse (TGD) communities who face discrimination in healthcare, and in cancer care specifically. If current federal protections are eliminated, enacting local non-discrimination policies may safeguard TGD individuals’ rights to access safe equitable cancer care. To determine the need for local policy change, we sought to assess the current protections based on gender identity and expression for patients at National Cancer Institute (NCI)-Designated Cancer Centers. Methods: Publicly available hospital non-discrimination policies and Patients’ Bill of Rights were examined from the main affiliated hospitals of each of the 62 NCI-Designated Cancer Centers, excluding laboratories. The policies were classified as clearly including gender identity and expression or not. McNemar’s Test calculated differences between non-discrimination policies and Patient’ Bill of Rights. Results: Of 62 institutions, 30 (48.4%) clearly included gender identity and expression in their hospital non-discrimination policies, whereas 45 (72.6%) included gender identity and expression in their Patients’ Bill of Rights ( p= 0.014). Thirty-seven (59.7%) institutions included gender identity and expression in only one of the documents (Table). Conclusions: NCI-Designated Cancer Centers do not consistently include gender identity and expression in publicly available non-discrimination documents. The discrepancy between Patients’ Bill of Rights documents and hospital non-discrimination policies suggests a difference between what institutions outwardly convey to patients and what they operationalize in their legal documents. Paired outcomes from 62 independent NCI-Designated Cancer Centers. [Table: see text]
QT assessments in oncology drug development and related labels.
Authors: Zheng Nan , Zhao Hong , Li Mike , Adeojo Lilian Wanjiku , Uppoor Visesh , Garnett Christine 
Published: May 2020

e14127 Background: A thorough QT (TQT) study, designed to evaluate whether a new drug excludes a small mean increase in the QTc interval (i.e., > 10 ms) which is considered to have low proarrhythmic risk, is often not feasible for oncology drugs. Alternative designs that assess the QTc changes in cancer patients are used to exclude large mean increases (i.e., > 20 ms) for drugs where the expected benefit outweighs the small proarrhythmic risk. A retrospective analysis was conducted to evaluate QT study designs and the consistency of QT labeling for oncology drugs. Methods: This analysis included FDA approved oncology drugs with QT studies reviewed by CDER’s Interdisciplinary Review Team as of 10/01/2019. Information collected included the clinical study design (i.e., TQT, alternative designs such as a sub-study in a Phase 2/3 trial), primary analysis (i.e., central tendency or concentration-QTc [CQT] analysis), QT findings at the therapeutic dose (i.e., the mean [M] and the upper bound of 90% confidence interval [UCI] of QTc changes), supportive data (i.e., nonclinical cardiac safety data, if applicable), conclusion of the QT assessment, and labeling statements in Section 12.2 (Pharmacodynamics) and Section 5 (Warnings & Precautions) of the product labels. Baseline QTc values in these alternative studies were compared to those in TQT studies across different therapeutic areas. Results: The analysis included 72 oncology drugs. The mean baseline QTc value is 411.2 ms in male patients (n = 6951) and 394.6 ms in male healthy volunteers (n = 22288), and 414.3 ms in female patients (n = 6412) and 408.8 ms in female healthy volunteers (n = 15682). Alternative study designs were used for 63 (87.5%) drugs while TQT study was only used for 9 (12.5%) drugs. CQT was used as the primary analysis for 11 (15.3%) drugs. Among the 72 product labels, 8 labels do not have QT information in Section 12.2 and 9 labels inconsistently describe the results of an alternative study. Warnings and Precautions for QT Prolongation in Section 5 of the labels were triggered by positive signals in the QT assessment or clinical trial safety monitoring experience. Conclusions: Cancer patients had higher QTc and less sex difference at baseline than healthy volunteers. QT labeling consistency in Section 12.2 could be improved by standardizing the description of study results based on QT study designs. Disclaimer: The contents reflect the views of the authors and should not be construed to represent the FDA's views or policies.
Achieving national cancer governance reform: Lessons from a successful academic, clinical, and community advocacy approach in New Zealand.
Authors: Jackson Christopher G. C. A. , Sarfati Diana 
Published: May 2020

e14131 Background: Cancer survival in New Zealand (NZ) is high in global terms but gains in outcome are less than in comparable countries over recent time cohorts. Outcomes of indigenous Māori New Zealanders are significantly worse for most major cancers. This is potentially due to decentralisation of cancer provision and lack of emphasis on national governance. Methods: In 2017, academics, clinicians and patient advocates embarked on a planned and sustained programme of advocacy with the goal of establishing a national cancer plan, centralised cancer governance, and publicly reportable cancer outcomes and quality indicators by region and ethnicity. Elements central to success were partnerships with politicians and opposition parties, building credible media voices, establishing international academic collaborations, clear problem identification, positive evidence-based policy solutions, sustained and consistent yet varied media messaging, and strong relatable patient stories with direct citizen engagement. Results: As a direct result, in 2019 the Government established a National Cancer Agency, updated the national cancer plan for the first time in 16 years, moved to dissolve regional cancer networks, and appointed a national director of cancer control. New funding specifically for cancer investment was also announced and commitments to additional funding have been made. We review the strategies that were most successful, challenges encountered, and outcomes achieved. Conclusions: Advocacy and collaboration between patients, academics and clinicians remains a powerful stimulus for meaningful policy change. Our approach can be instructive for other countries where national cancer control and governmental leadership are faltering.