Global Development Program Research Articles

P015: A phase IV protocol for a real world study on the use of low dose methoxyflurane (PENTHROX™) for the treatment of moderate to severe trauma pain in the Canadian emergency department (ADVANCE-ED)

Introduction: Pain is a significant driver of demand in emergency care and 65% of adult patients with trauma also report moderate to severe pain. Inhaled low dose methoxyflurane (MEOF) a rapid-acting patient administered inhalational analgesic was recently approved in Canada for the short-term relief of moderate to severe acute pain associated with trauma or interventional medical procedures in conscious adult patients. This study will generate real-world evidence to complement the global clinical development program through evaluation of the effectiveness of MEOF in Canadian emergency departments. Methods: This is a phase IV, prospective open label, multi-centre study. Approximately 100 adult (≥18 yrs) patients with moderate to severe acute pain (NRS0-10≥4) associated with single system trauma will be enrolled at 5-10 EDs across Canada. Patients will receive a single treatment of up to 2 x 3 mL MEOF (2nd 3 mL to be provided only upon request), self-administered by the patient under medical supervision. Rescue medication will be permitted at any time, if required. Results: Planned Assessments and Outcome Measures: Pain will be assessed using the NRS0-10 at 4 time points: screening/triage, 5 minutes and 20 minutes post-start of administration (STA) of MEOF, and when ready for discharge. Secondary assessments will include the speed of action of analgesia (from STA of MEOF); patient and physician satisfaction with treatment (as assessed through Global Medical Performance (GMP) at 20 minutes post-STA and when ready for discharge); patient and physician fulfilment of pain relief expectations (assessed when ready for discharge); use of rescue medication and treatment-emergent adverse events. Exploratory outcomes will include the time to disposition, time to readiness for discharge and responder analysis. The primary outcome measure will be the change in pain intensity over 20 minutes from the start of administration of MEOF as measured on the NRS0-10. Conclusion: We report on the methodology of a phase IV, prospective open label, multi-centre study, evaluating the use of MEOF for the management of acute traumatic pain in Canadian Emergency Departments.

Pharmacokinetics, safety, and efficacy of tapentadol oral solution for treating moderate to severe pain in pediatric patients.

Background: This trial is part of the global pediatric clinical development program investigating the administration of the strong analgesic tapentadol in children and adolescents.Patients and methods: The single site, open-label phase 2 trial evaluated the pharmacokinetic profile of tapentadol and its major metabolite, tapentadol-O-glucuronide, as well as safety and tolerability and efficacy of a single dose of tapentadol oral solution (1 mg/kg) in patients (2 to <18 years) undergoing dental, ear, nose, or throat surgery. Blood sampling and pain intensity measurements were conducted using age-appropriate schedules and rating scales, respectively. Adverse events were monitored throughout the trial.Results: Sixty-six patients were treated. They were stratified by age: Group 1 (12 to <18 years), n=21; Group 2 (6 to <12 years), n=28; and Groups 3 (3 to <6 years) and 4 (2 to <3 years), n=17. Serum tapentadol concentrations observed in these pediatric patients were within the range observed in adults after administration of a single tapentadol immediate-release dose (50–100 mg), whereas those of the metabolite tapentadol-O-glucuronide were within the same range or lower than in adults who received comparable single doses of tapentadol. Pain intensity improved over time across all age groups. The most common treatment-emergent adverse events were nausea (24.2%), vomiting (16.7%), dizziness (9.1%), and headache (6.1%).Conclusion: A single dose of tapentadol oral solution (1 mg/kg) administered to pediatric patients (2 to <18 years) resulted in serum tapentadol concentrations within the targeted range shown to be safe and efficacious in adults. Tapentadol demonstrated good tolerability and safety; within the limitations of the trial design, improvements in postsurgical pain intensity were observed across the age groups. Tapentadol may provide a new treatment option in the management of moderate to severe pediatric pain.

CUBES: A practical toolkit to measure enablers and barriers to behavior for effective intervention design

A pressing goal in global development and other sectors is often to understand what drives people’s behaviors, and how to influence them. Yet designing behavior change interventions is often an unsystematic process, hobbled by insufficient understanding of contextual and perceptual behavioral drivers and a narrow focus on limited research methods to assess them. We propose a toolkit (CUBES) of two solutions to help programs arrive at more effective interventions. First, we introduce a novel framework of behavior, which is a practical tool for programs to structure potential drivers and match corresponding interventions. This evidence-based framework was developed through extensive cross-sectoral literature research and refined through application in large-scale global development programs. Second, we propose a set of descriptive, experimental, and simulation approaches that can enhance and expand the methods commonly used in global development. Since not all methods are equally suited to capture the different types of drivers of behavior, we present a decision aid for method selection. We recommend that existing commonly used methods, such as observations and surveys, use CUBES as a scaffold and incorporate validated measures of specific types of drivers in order to comprehensively test all the potential components of a target behavior. We also recommend under-used methods from sectors such as market research, experimental psychology, and decision science, which programs can use to extend their toolkit and test the importance and impact of key enablers and barriers. The CUBES toolkit enables programs across sectors to streamline the process of conceptualizing, designing, and optimizing interventions, and ultimately to change behaviors and achieve targeted outcomes.

Risks of Biological Invasion on the Belt and Road

China's Belt and Road Initiative (BRI) is an unprecedented global development program that involves nearly half of the world's countries [1]. Itnot only will have economic and political influences, but also may generate multiple environmental challenges and is a focus of considerable academic and public concerns [2-6]. The Chinese government expects BRI to be a sustainable development, paying equal attention to economic development and environmental conservation [7].However, BRI's high expenditure on infrastructure construction, by accelerating trade andtransportation, is likely to promote alien species invasions [5], one of the primary anthropogenic threats to global biodiversity [8]. BRI countries may have different susceptibilities to invasive species due to different financial and response capacities [9]. Moreover, these countries overlap 27 of 35 recognized global biodiversity hotspots [10]. Identifying those areas with high-invasionrisks, and species with high invasive potentials within BRI countries, is therefore of vital importance for the sustainable implementation of the BRI, and the development of early, economical, and effective biosecurity strategies [11]. In response, we present here a comprehensive study to evaluate invasion risks by alien vertebrates within BRI. We identified a total of 14 invasion hotspots, the majority of which fall along the six proposed BRI economic corridors, with the proportion of grid cells in invasion hotspots 1.6 times higher than other regions. Based on our results, we recommend the initiation of a project targeting early prevention, strict surveillance, rapid response, and effective control of alien species in BRI countries to ensure that this development is sustainable.

Pharmacokinetics and Pharmacodynamics of the BACE1 Inhibitor Verubecestat (MK-8931) in Healthy Japanese Adults: A Randomized, Placebo-Controlled Study.

β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the production of β-amyloid (Aβ) peptides and is considered a potential treatment target for Alzheimer's disease (AD). To support Japan's participation in the global clinical development program, we characterized the safety, pharmacokinetics (PKs), and pharmacodynamics of the BACE1 inhibitor verubecestat (MK-8931) in 24 healthy Japanese adults in a two-part, single-center, randomized, placebo-controlled phase I trial (protocol MK-8931-007) and compared the results with historical data from non-Japanese subjects. Both single (20, 100, and 450mg) and multiple (80 and 150mg once daily for 14days) doses of verubecestat were well tolerated. Verubecestat's PK profile was similar in Japanese and non-Japanese subjects. Verubecestat also reduced mean cerebrospinal fluid concentrations of the Aβ proteins Aβ40, Aβ42, and soluble β fragment of amyloid precursor protein; thelevel of reduction was comparable between Japanese and non-Japanese subjects. These results support the continued global development of verubecestat as a potential disease-modifying agent for Japanese and non-Japanese subjects who are at risk for developing AD.

“A woman CEO? You’d better think twice!”

PurposeThe purpose of this paper is to explore how multinational corporations’ (MNCs’) women leaders in South Korea (Korea) have overcome career challenges in the process of becoming CEOs. The two guiding questions for this study included: what career challenges have MNCs’ women leaders in Korea faced to become CEOs? How have they overcome their career challenges?Design/methodology/approachThe authors used a basic qualitative research design, the goal of which is to understand how people make sense of their lives and experiences. Qualitative data were collected by semi-structured interviews with 15 women CEOs at MNCs in Korea to capture their lived experiences (challenges and strategies) in their careers. The authors used NVivo 11, a qualitative data analysis software, to analyze the interview data.FindingsFrom data analysis, the authors identified five themes including: becoming a CEO, key success factors, MNC culture, career challenges and career development strategies. The authors found that in the process of becoming CEOs, 15 women leaders faced career challenges that are largely generated by traditional culture, work stress and work–life balance. The authors also found that the women leaders became CEOs through diverse on-the-job experiences (e.g. marketing and sales) and positions (e.g. managers, senior managers and regional directors) with organizational support (e.g. supervisor support).Research limitations/implicationsGiven research on organizational support for leadership, human resource practices and working conditions, this study’s findings have qualitatively confirmed the importance of organizational support for women CEOs’ career success. For theory building in women in leadership, the authors suggest that researchers investigate the complex process of becoming women CEOs, including their early experiences in their career in tandem with family background, organizational climate and national culture.Practical implicationsThe study findings on women CEOs’ career strategies can be used as a reference for women in the leadership pipeline who aspire to take leadership positions in organizations. A lack of role models or mentors for women leaders is one of the reasons why women give up on their career. Learning career strategies (e.g. global development programs, mentoring and networks) that women CEOs have employed to overcome their career challenges can help women in the leadership pipeline from their early career on.Originality/valueThe authors found that both internal and external factors combined were instrumental in the women CEOs’ career success. What stood out from this study was that the women’s desirable personality attributes might not have materialized without the MNC culture that has been supportive for these women. The women CEOs shared their company’s values and philosophy that is based on gender equality, received supervisor support that is crucial for their career success, experienced diverse jobs and positions along the way and were recognized for their work ethic. Given research on women leaders conducted largely in western contexts, this qualitative study on the lived experiences of women CEOs in MNCs contributes to emerging non-western research by capturing the importance of culture that is uniquely Korean.

Baseline Assessment of the Evolving 2017 eClinical Landscape.

The volume and diversity of data collected to support each clinical study has increased dramatically in response to the rising scope and complexity of global drug development programs. The Tufts Center for the Study of Drug Development conducted an online survey of 257 unique global companies-77% drug development sponsors and 23% contract service providers-to assess clinical data management practices and experiences. Study results indicate that companies are using an average of 6 different applications to support each clinical study and that companies are collecting a range of data types including that from case report forms, lab procedures, pharmacokinetics, biomarker, outcomes assessment, mobile health, and social media. Companies report that the primary electronic data capture (EDC) is capturing traditional data types but not many of the newer ones. Respondents report spending an average of 68.3 days to build and release a study database, 8.1 days between the patient visit and when that patient's data are entered into the EDC system, and 36.3 days on average to lock the database following the last patient last visit. Average cycle time durations are longer and more variable than those observed ten years ago. Subgroup differences (eg, by company size and company type) and factors contributing to data management cycle time and experience are discussed.

How Does Governance Modify the Relationship between Public Finance and Economic Growth: A Global Analysis

How Does Governance Modify the Relationship between Public Finance and Economic Growth: A Global Analysis

Paediatric extrapolation: A necessary paradigm shift.

Legislative initiatives have been successful in increasing the availability of approved therapies for paediatric patients. However, additional measures to ensure the timely completion of paediatric studies are necessary to further increase the number of medicines available to children. Over the last 3 years, international experts convened to revise the ICH E11 guideline on clinical investigations of medicinal products in paediatric populations to harmonize approaches to paediatric extrapolation, striving to reduce substantial differences between regions in the acceptance of data for global paediatric medicine development programmes. Several areas of therapeutics development in children, such as human immunodeficiency virus and partial-onset seizures, have been streamlined and require fewer children enrolled in clinical trials because of the appropriate application of paediatric extrapolation. Based on this experience, it is clear that for paediatric extrapolation strategies to reach their full potential there is the need to understand the quality and quantity of data, often collected in adult patients, that will inform the appropriateness of the use of paediatric extrapolation, as well as to identify gaps in knowledge with respect to disease pathophysiology, organ maturation or drug target ontogeny. The generation of information that enhances our current understanding of these gaps in knowledge can further decrease the need for larger, paediatric clinical trials and can increase the efficiency of paediatric therapeutics development as well as protect children from participation in unnecessary studies. We hope that this publication will increase awareness, input and support from all the stakeholders involved in paediatric therapeutics development.

The global leadership capacity wheel

PurposeThe purpose of this paper was to examine the definitions of global leadership and indigenous leadership, identify leadership capacities inherent in human resource development (HRD) and determine relationships of the three as a means to develop a model to aid and guide opportunities for future research.Design/methodology/approachFollowing a two-stage integrative literature review of HRD, global and indigenous leadership literature, the grounded theory constant comparative method established 31 positive and 1 negative leadership domains, and respective capacities, and compare domains from literature.FindingsThe Global Leadership Capacity Wheel informs researchers of strengths and areas for additional research, has resulted in a more complete model of global leadership and calls for increased clarity for leadership capacity model development, especially for complex, global environments and local constructs and theories.Research limitations/implicationsAlthough the literature had adequate representation in the business and organizational acumen and managing people and relationships central global leadership domains, more research and reporting is required for managing self and indigenous leadership capacity development subdomains.Practical implicationsLeadership development is a high priority and core function of HRD. The Global Leadership Capacity Wheel provides a tool for scholars and practitioners to guide global leadership development programs and research.Social implicationsUnderstanding the relationships of leadership capacities from global and indigenous perspectives is helpful to examine cultural, identity and macro-contextual dimensions and their influence on leadership.Originality/valueThe Global Leadership Capacity Wheel provides a type of road-map, a holistic representation, in the context of developing global leaders in today’s complex environment.

How can academic-policy collaboration be more effective? A stewardship approach to engaged scholarship in the case of SME internationalization

In response to calls for more policy-relevant academic research, this paper undertakes a stewardship approach to examine an engaged scholarship policy programme targeted at supporting the internationalization of Small and Medium-Sized Enterprises (SMEs) in Scotland, namely the Global Companies Development Programme (GCDP). The study was undertaken by academics and included a combined formal evaluation and research study, a follow-up workshop and group interviews over a ten-year-period. This study extends the stewardship approach to the engaged scholarship context. The findings suggest that stakeholders view their collaboration as a “supra-organizational” formation through which they can identify and empathize with its objectives; require skilful boundary spanners who consistently promote the objectives of the collaboration in the participating organizations; and, accentuate effective knowledge generation and transfer to SME internationalization activities that reflect the outcomes of their collaboration. We discuss policy implications for the development of private-public and inter-agency partnerships.

A simple metric for a complex outcome: proposing a sustainment index for health indicators

BackgroundSustainability is, at least in principle, an important criterion for evaluating global health and development programs. The absence of shared metrics for success or achievements in sustainability is however critically lacking. We propose a simple metric, free of causal inference, which can be used to test different empirical models for the sustainment of health outcomes.MethodsWe follow the suggestion of Chambers and use “sustainment” to refer to the verifiable and measured extent to which a health indicator has evolved over time. The sustainment index of a health indicator (Y) advanced by a program is based on a simple-to-calculate approximation of the derivative of Y over time (T0: baseline, T1: endline, and T2: post-project), based on the ratio of the slope of YT1-T2 over YT0-T1. SI(Y) = 1+ (YT1-T2 / YT0-T1).ResultsThis construct provides three clear benchmarks: SI = 0, when the health indicator returns to baseline value post-project (YT2 = YT0); SI = 1, when the endline-post-project trend is a plateau; and SI = 2, when the progress slope during program is uninterrupted post-program. We find strong correlation (r2 = 0.922) between the SI and independent practitioners’ rating of indicator trends. The SI shows different levels of achieved sustainment for a range of indicators in a published ex-post sustainability study. And we find that the SI can be computed for large national datasets for two types of indicators.ConclusionsThe Sustainment Index has limitations and conditions of applicability, but it can be applied to different datasets and studies to provide a reliable dependent measure of the level of sustainment of health outcomes from one period of time to the next. The Index will need additional testing, and future evaluation-research work will need to consider index performance under different situations. The Sustainment Index has the potential to provide a standard metric to build evidence through more systematic research on sustainment and sustainability.

The Potential of Distributed Energy Resources in Building Sustainable Campus: The Case of Sichuan University

Distributed energy resources systems are decentralized, modular and more flexible technologies. These systems can comprise multiple generation and storage components. Sichuan University (SCU) has joined Global Urban Development program, and takes part in Sustainability Tracking, Assessment & Rating System, aims at a sustainable campus. So we investigated the potential of distributed energy resources, e.g. solar power, that can be used in SCU. Firstly, we build 4 micro-grids with a total 156 Kw PV capacities to collect the power generation data. The total roof area of SCU Jiangan campus is 165701 m2, and the estimated installed capacity is 8.3MW-11.6MW. Based on this data, 33% ~ 46% power cost can be covered by PV power generation.

Analyzing the greenhouse gas impact potential of smallholder development actions across a global food security program

This article analyses the greenhouse gas (GHG) impact potential of improved management practices and technologies for smallholder agriculture promoted under a global food security development program. Under ‘business-as-usual’ development, global studies on the future of agriculture to 2050 project considerable increases in total food production and cultivated area. Conventional cropland intensification and conversion of natural vegetation typically result in increased GHG emissions and loss of carbon stocks. There is a strong need to understand the potential greenhouse gas impacts of agricultural development programs intended to achieve large-scale change, and to identify pathways of smallholder agricultural development that can achieve food security and agricultural production growth without drastic increases in GHG emissions.In an analysis of 134 crop and livestock production systems in 15 countries with reported impacts on 4.8 million ha, improved management practices and technologies by smallholder farmers significantly reduce GHG emission intensity of agricultural production, increase yields and reduce post-harvest losses, while either decreasing or only moderately increasing net GHG emissions per area. Investments in both production and post-harvest stages meaningfully reduced GHG emission intensity, contributing to low emission development. We present average impacts on net GHG emissions per hectare and GHG emission intensity, while not providing detailed statistics of GHG impacts at scale that are associated to additional uncertainties. While reported improvements in smallholder systems effectively reduce future GHG emissions compared to business-as-usual development, these contributions are insufficient to significantly reduce net GHG emission in agriculture beyond current levels, particularly if future agricultural production grows at projected rates.

A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases.

Tocilizumab (TCZ) is the first humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody approved for the treatment of patients with rheumatoid arthritis (RA), Castleman's disease, polyarticular and systemic juvenile idiopathic arthritis, and, most recently, giant cell arteritis as well as for the treatment of chimeric antigen receptor T cell therapy-induced cytokine release syndrome. The global clinical development program for TCZ provides a wealth of clinical data on intravenous TCZ, and more recent studies in patients with RA have provided evidence characterizing the role of intravenous TCZ as monotherapy in early disease and led to the introduction of a subcutaneous formulation of TCZ. In addition, recently published open-label extension and observational studies continue to support the long-term efficacy and safety of TCZ in both clinical trial and real-world settings. Given the involvement of IL-6-mediated signaling in inflammatory disorders, TCZ is also being investigated in other immunological diseases. In particular, a phase 2 trial on the safety and efficacy of subcutaneous TCZ in adults with systemic sclerosis shows clinically relevant improvements in skin sclerosis and lung function in these patients. Another anti-IL-6 receptor agent, sarilumab, targeting the IL6 receptor alpha subunit,was recently approved for the treatment of patients with RA, although long-term data for this biologic are not yet published. In this article we review the placement of TCZ in current treatment guidelines; recent clinical trial data, including quality of life in patients with RA; recent updates to the TCZ safety profile; recent investigations of TCZ in other immunological diseases; and the clinical development of other novel IL-6-targeted agents.

Liver Safety of Fasiglifam (TAK-875) in Patients with Type 2 Diabetes: Review of the Global Clinical Trial Experience

Fasiglifam (TAK-875) is a G protein-coupled receptor 40 agonist that was being investigated for treatment of type 2 diabetes mellitus (T2DM). A development program was terminated late in phase III clinical trials due to liver safety concerns. The liver safety of fasiglifam was assessed from data based on six phase II and nine phase III double-blind studies and two open-label studies with emphasis on pooled data from 15 double-blind studies from both global and Japanese development programs. Taking into consideration different daily doses of fasiglifam administered in clinical studies, the primary comparisons were between all patients exposed to fasiglifam (any dose) versus placebo, and, where applicable, versus the two active comparators, sitagliptin or glimepiride. A Liver Safety Evaluation Committee consisting of hepatologists blinded to treatment assignments evaluated hepatic adverse events (AEs) and serious AEs (SAEs) for causal relationship to study drug. The analysis included data from 9139 patients with T2DM in 15 double-blind controlled studies who received either fasiglifam (n=5359, fasiglifam group), fasiglifam and sitagliptin (n=123), or a comparator agent (n=3657, non-exposed group consisting of placebo and other antidiabetic agents). Exposure to treatment for more than 1year ranged from 249 patients in the placebo arm, to 370 patients in the glimepiride arm and 617 patients in the fasiglifam 50mg arm. The primary focus of the analysis was on the hepatic safety of fasiglifam. The overall safety profile based on treatment-emergent AEs (TEAEs), SAEs, deaths, and withdrawal due to AEs was similar between fasiglifam and placebo (excluding liver test abnormalities). However, there was an increased incidence rate of serum alanine aminotransferase (ALT) elevations>3×upper limit of normal (ULN), 5×ULN, and 10×ULN in fasiglifam-treated patients compared with those treated with placebo or active comparators. ALT elevations>3×ULN for fasiglifam were 2.7% compared with 0.8 and 0.5% for the active comparators and placebo. There did not appear to be a clear dose response in incidence of ALT elevations between patients receiving 25 or 50mg daily. The cumulative incidence of elevations in serum ALT>3×ULN was higher in the first 6months of treatment with fasiglifam compared with both placebo and the active comparators, but the rate of new ALT elevations appeared to be similar across all treatment groups thereafter. No demographic or baseline patient characteristics were identified to predict elevations exceeding ALT>3×ULN in fasiglifam-treated patients. The pattern of liver injury with fasiglifam was hepatocellular, and there were no reports of liver-related deaths, liver failure or life-threatening liver injury. Most fasiglifam-associated ALT elevations were asymptomatic and resolved promptly upon discontinuing treatment, but in two patients the recovery was prolonged. Importantly, three important serious liver injury cases were identified among fasiglifam-treated patients; one case was adjudicated to be a clear Hy's Law case and the two remaining cases were considered to closely approximate Hy's Law cases. Although the incidence of overall AEs, SAEs, and deaths was similar between fasiglifam and placebo, a liver signal was identified based primarily on the difference in liver chemistry values in the fasiglifam group compared with the placebo and active comparator groups. Three serious liver injuries were attributed to fasiglifam treatment. Clinical development of fasiglifam was halted due to these liver safety concerns.

Abstract P1-09-11: A phase Ib study of oral administration of lucitanib in combination with fulvestrant in patients with HR+ metastatic breast cancer (mBC)

Abstract FGFR1 amplification could mediate resistance to endocrine therapy and FGFR1 inhibition reverses this resistance. This phase Ib seeks to evaluate whether the combination of lucitanib, a potent FGFR/VEGFR/PDFGR inhibitor, in combination with fulvestrant, an endocrine agent, reverses resistance to fulvestrant. Eligible patients for this study were postmenopausal with ER+/HER2- mBC and have relapsed during or after treatment with fulvestrant. There were 2 parts in the study: a dose allocation to assess the tolerability of the combination in terms of DLTs and MTD using a modified Continual Reassessment Method (mCRM) [part I] and a dose expansion, with patients assigned to 2 different cohorts based on FGFR amplification, to further evaluate the tolerability of the combination and to identify the recommended phase II dose (RP2D) [part II]. Surrogate target hitting biomarkers were also dosed at baseline and on-treatment. The sponsor decided to halt the clinical development in mBC indication and the study was prematurely terminated after 18 patients (15 in part I and 3 in part II). The presentation will focus on these 18 patients. Patients had ECOG PS 0 or 1 and median number of previous treatments in metastatic setting was 3. Two doses of lucitanib (10mg daily n=9 and 12.5mg daily n=6) in combination with 500 mg/month of fulvestrant were tested in part I. At the 10mg dose level, one patient experienced a DLT (grade 3 hypertension). Based on global lucitanib development program data, it was decided to start Part II with lucitanib 10mg daily. The most common related grade ≥3 toxicities occurring in more than 10% of patients were hypertension (78%) and asthenia (22%). All patients required at least one dose interruption mainly for toxicities, while 13 patients (72%) required at least a dose reduction for toxicities. Thirteen patients (72%) withdrew from the study for disease progression, 3 (17%) for adverse events (at 10mg) and 2 (11%) for non-medical reasons. Three patients achieved a confirmed partial response (as per RECIST v1.1), one at 10mg and two at 12.5mg. About 55% of the patients experienced clinical benefit with a median duration of the benefit of 39.6 weeks and a maximun duration of the benefit of 79.1 weeks for 1 patient (PR at Cycle 4). Biomarker modulations were consistent with lucitanib mode of action; targeting VEGFRs (significant increase of VEGFA, IL8, PlGF) and FGFR1 (significant increase of FGF23). The combination is feasible but requires close patient monitoring and intensive management of adverse events. Those are in line with the anti-angiogenic activity of lucitanib. 10mg (N=12)12.5mg (N=6)All (N=18)Objective Response Rate (ORR)n(%) 11 (8.3)2 (33.3)3 (16.7) 95% CI 3[1.5;35.4][9.7;70.0][5.8;39.2]Clinical Benefit Rate (CBR)n(%) 24 (33.3)6 (100.0)10 (55.6) 95% CI 3[13.8;61.0][61.0;100.0][33.7;75.4]Duration of Clinical Benefitmedian (weeks)28.171.339.6 95% CI 3[27.9; 32.7][29.1; 79.1][27.9; 79.1]1: CR or PR 2: CR or PR or stabilization (SD or NonCR/NonPD) &amp;gt;24 weeks or at end of cycle 6 3: 95% Wilson method of Confidence interval of the estimate Citation Format: Campone M, Bachelot T, Penault-Llorca F, Pallis A, Agrapart V, Pierrat M-J, Poirot C, Paux G, Dubois F, Xuereb L, Robert R, Andre F. A phase Ib study of oral administration of lucitanib in combination with fulvestrant in patients with HR+ metastatic breast cancer (mBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-09-11.

A research utilisation framework for informing global health and development policies and programmes

A research utilisation framework for informing global health and development policies and programmes

Global Human Resource Development Program for Nuclear Safety and Security(3)

Global Human Resource Development Program for Nuclear Safety and Security(3)

Global Human Resource Development Program for Nuclear Safety and Security(1)

東京工業大学では，全寮制の｢世界原子力安全・セキュリティ道場｣を基盤として，演習・実習を含むコースワークや国内外インターンシップ等を重視した修士・博士一貫型の学位プログラムによって，｢人類の生存基盤を脅かす核拡散，核テロ，大規模な原子力災害や緊急被ばく問題等のグローバルな原子力危機｣の分野において，高い国際交渉能力を有し，国内外の原子力関連の産官学界で国際的リーダーとして活躍する人材｢グローバル原子力安全・セキュリティ・エージェント｣を養成している。本稿では本学位プログラムの概要と成果について述べる。