Towards sustainability and affordability of expensive cell and gene therapies? Applying a cost-based pricing model to estimate prices for Libmeldy and Zolgensma

Background aimsDrug prices are regarded as one of the most influential factors in determining accessibility and affordability to novel therapies. Cell and gene therapies such as OTL-200 (brand name: Libmeldy) and AVXS-101 (brand name: Zolgensma) with (expected) list prices of 3.0 million EUR and 1.9 million EUR per treatment, respectively, spark a global debate on the affordability of such therapies. The aim of this study was to use a recently published cost-based pricing model to calculate prices for cell and gene therapies, with OTL-200 and AVXS-101 as case study examples.MethodsUsing the pricing model proposed by Uyl-de Groot and Löwenberg, we estimated a price for both therapies. We searched the literature and online public sources to estimate (i) research and development (R&D) expenses adjusted for risk of failure and cost of capital, (ii) the eligible patient population and (iii) costs of drug manufacturing to calculate a base-case price for OTL-200 and AVXS-101. All model input parameters were varied in a stepwise, deterministic sensitivity analysis and scenario analyses to assess their impact on the calculated prices.ResultsPrices for OTL-200 and AVXS-101 were estimated at 1 048 138 EUR and 380 444 EUR per treatment, respectively. In deterministic sensitivity analyses, varying R&D estimates had the greatest impact on the price for OTL-200, whereas for AVXS-101, changes in the profit margin changed the calculated price substantially. Highest prices in scenario analyses were achieved when assuming the lowest number of patients for OTL-200 and highest R&D expenses for AVXS-101. The lowest R&D expenses scenario resulted in lowest prices for either therapy.ConclusionsOur results show that, using the proposed model, prices for both OTL-200 and AVXS-101 lie substantially below the currently (proposed) list prices for both therapies. Nevertheless, the uncertainty of the used model input parameters is considerable, which translates in a wide range of estimated prices. This is mainly because of a lack of transparency from pharmaceutical companies regarding R&D expenses and the costs of drug manufacturing. Simultaneously, the disease indications for both therapies remain heavily understudied in terms of their epidemiological profile. Despite the considerable variation in the estimated prices, our results may support the public debate on value-based and cost-based pricing models, and on “fair” drug prices in general.     

De novo discovery of antibody drugs – great promise demands scrutiny

ABSTRACT

We live in an era of rapidly advancing computing capacity and algorithmic sophistication. “Big data” and “artificial intelligence”find progressively wider use in all spheres of human activity, including healthcare. A diverse array of computational technologies is being applied with increasing frequency to antibody drug research and development (R&D). Their successful applications are met with great interest due to the potential for accelerating and streamlining the antibody R&D process. While this excitement is very likely justified in the long term, it is less likely that the transition from the first use to routine practice will escape challenges that other new technologies had experienced before they began to blossom. This transition typically requires many cycles of iterative learning that rely on the deconstruction of the technology to understand its pitfalls and define vectors for optimization. The study by Vasquez et al. identifies a key obstacle to such learning: the lack of transparency regarding methodology in computational antibody design reports, which has the potential to mislead the community efforts     

Genomics,ICT and the formation of R&D networks

Research in genomics is an example of changes induced by information and communication technologies (ICT). The emergence of interconnected ICT support for scientific work and the handling of information have changed the challenges in genomics as well as other scientific fields. The promises are significant but a large degree of uncertainty remains. While the information space is opened up, R&D cooperation essential to reaping the benefits for companies is still difficult. Moreover, in order to benefit in full from the possibility to combine knowledge on a larger scale, knowledge repositories and places of knowledge creation need to be combined. This paper discusses the new strategies of information networking between companies that emerges in response to this challenge. It concludes with an outline of a research agenda for genomics and society.     

政府补偿与监管机制改革对公立医疗卫生机构科教与学科建设的影响分析

目的 分析政府补偿与监管机制改革对公立医疗卫生机构教学、科研以及学科建设的影响。方法 通过对上海市闵行区的机构调查,收集并分析2008—2012年3所公立综合性医院和12家社区卫生服务中心的医学教育、科研项目、论文发表及重点学科建设状况的相关数据。结果 闵行区公立综合性医院和社区卫生服务中心的医学教育和科研能力有所提升,重点学科建设也有所加强;但仍然存在教学能力薄弱,科研水平层次偏低,缺乏高质量的重点学科等问题。结论 政府补偿与监管机制改革在一定程度上强化了公立医疗机构的医学教育、科研能力和学科建设,但未来需进一步加大对科教和学科建设的鼓励和支持力度。     

2012–13 Upcoming meetings

The Winter 2012–13 conference season provides ample opportunities to attend meetings that feature topics relevant to antibody research and development (R&D). Meetings such as these serve critical informational and educational functions and are key networking opportunities. Locations are spread throughout the world, reflecting the global nature of antibody R&D.

Please note that Upcoming meetings lists will no longer be included in the print version of mAbs starting with the January/February 2013 issue. Please visit the mAbs home page to find an online meeting list: www.landesbioscience.com/journals/mabs/     

医药 CRO 专题报告——蓝海市场，强者恒强

随着全球制药企业研发投资成本加大、研发周期变长、研发成功率降低,作为社会分工专业化的产物,CRO 企业凭借其低成本、高效率、 多服务的特点,快速发展,且服务范畴已涵盖药物研发的整个过程,成为医药研发产业链中不可缺少的环节。报告采用文献调研、数据库检索、 数据统计与分析等定性定量研究方法,从发展概况、发展策略、竞争格局、企业布局等角度对国内外医药 CRO 领域进行多角度、多层次的 分析,旨在为相关企业确定产品研发思路、制定市场策略提供线索和参考。     

The Polish Centre for Life Cycle Assessment—the centre for life cycle assessment in Poland

The Polish Centre for life cycle assessment (LCA) is a non-profit organization founded in 2009 following the initiative of people involved in Polish scientific and R&D centers dealing with LCA. The role, mission as well structure and organization of PCLCA have been presented. Moreover, the current state of LCA implementation in Poland has been mentioned. However, LCA has been mainly used for scientific research less by industry and business.     

Participation of women medical Physicists in European scientific events: The European experience

PurposeThough the number of women scientists is increasing over the years, studies show that they are still under-represented in leadership roles. The purpose of this work is to establish the percentage of women Medical Physicists (wMPs) that have participated in European scientific events and evaluate it as an indication of the current position of women in the field of Medical Physics in Europe and to propose possible ways to encourage their participation.Materials and MethodsData regarding the participants in European scientific events of Medical Physics were collected. The participants were divided into categories according to the program of the events and their gender was identified. The percentage of wMPs in each category was evaluated.ResultsThe participation of wMPs attending courses is greater than 50%. The categories with the greatest participation are “Organizing Committees”, “Chairpersons-Moderators” and “Oral Presentations”. The categories with the lower participation of wMPs are “Scientific Committee”, “Symposiums” and “Invited Speakers”. None of wMPs were represented as “Course Directors”.ConclusionsThe attendance of wMPs in courses is slightly greater than average. However, wMPs do not have an equally important recognition in special invited roles in conferences. They are still under-represented in “Scientific Committees”, “Invited Speakers”, “Symposiums” and “Course directors”. wMPs should be encouraged to participate even more actively in European conferences and the organizing committees should invite more wMPs in special roles. More studies concerning the status of female MPs in each country separately should be encouraged as they will help in understanding the position of wMPS in Europe.     

A Survey of Bioenergy Research in Forest Service Research and Development

Forest biomass represents 25–30 % of the annual biomass available in the USA for conversion into bio-based fuels, bio-based chemicals, and bioproducts in general. The USDA Forest Service Research and Development (R&D) has been focused on producing products from forest biomass since its inception in 1905, with direct combustion, solid sawn lumber, pulp and paper, ethanol as fuel, and silvichemicals all among the mission areas of product research and development. The renewed national interest in biomass conversion to fuels and chemicals is supportive of the most critical need of USDA Forest Service R&D, uses for small-diameter trees and other forest biomass that needs to be removed in the fuel mitigation–fire suppression and forest restoration work of the USDA Forest Service. This paper will summarize the recent USDA Forest Service research on direct combustion, fuel pellets, and conversion of forest biomass to ethanol, both as stand-alone biorefinery processes and as an addition to the traditional wood pulping process.     

Phenotyping hepatocellular metabolism using uniformly labeled carbon-13 molecular probes and LC-HRMS stable isotope tracing

Metabolite stable isotope tracing is a powerful bioanalytical strategy that has the potential to unravel phenotypic markers of early pharmaceutical efficacy by monitoring enzymatic incorporation of carbon-13 atoms into targeted pathways over time. The practice of probing biological systems with carbon-13 labeled molecules using broad MS-based screens has been utilized for many years in academic laboratories but has had limited application in the pharmaceutical R&D environment. The goal of this work was to establish a LCMS analytical workflow that was capable of monitoring carbon-13 isotope changes in glycolysis, the TCA and urea cycles, and non-essential amino acid metabolism. This work applies a standardized protein precipitation with 80% cold methanol and two distinct reverse-phase ion-pair liquid chromatography methods coupled to either a positive- or negative-ion mode high-resolution accurate mass spectrometry screening method. The data herein combines thousands of single-point peak integrations into a novel metabolite network map as a visualization aid to probe and monitor stable isotope incorporation in murine hepatocytes using uniformly labeled ¹³C₆ glucose, ¹³C₃ lactate, and ¹³C₅ glutamine. This work also demonstrates that nitrogen metabolism may have a large influence on the TCA cycle and gluconeogenic carbon fluxes in hepatocyte cell culture.     

Muthi to medicine

The limited commercial opportunity for bioprospecting for isolated pure natural compounds or their derivatives from plants for novel pharmaceuticals is discussed. A broad overview of the key research inputs involved in the commercialisation of indigenous medicinal plants as botanical medicines is given to assist young researchers in contextualising research from an industry perspective, and to encourage university-industry collaboration. Compliance with the Biodiversity Act of 2004, and the regulations under this Act is stressed. The chain of research and development (R&D) activities is briefly described including ethnobotanical research, raw material supply, identification of active compounds, extract development, absorption studies, formulation development, in vitro, in vivo, and clinical safety and efficacy studies, and protection of intellectual property. Ultimately obtaining international marketing authorization for a novel botanical medicine is a lengthy and costly undertaking, with high risk of failure. Elements of botanical medicine R&D can be applied to functional foods, novel foods and personal care products, which can reach the market faster and with less risk than botanical medicines.     

基于论文和专利的中美脑科学领域对比研究

脑科学是生命科学领域的研究前沿和热点,美国是该领域的科技强国。本文基于科技论文和专利数据,利用文献计量学的定量分析方法,比较中国和美国在脑科学领域的理论研究和应用研究的差距。结果表明,基于论文分析的理论研究对比,发现中国较美国起步晚,目前论文数量上的差距正在缩小,但学术影响力的差距较大;基于专利分析的应用研究对比,发现中国在专利申请数量上已略超过美国,但在代表专利技术价值和市场价值的国际专利数量、技术布局、龙头企业及企业参与研发比重等方面,差距还非常之大。     

An Autonomic Reservoir Framework for the Stochastic Optimization of Well Placement

The adequate location of wells in oil and environmental applications has a significant economic impact on reservoir management. However, the determination of optimal well locations is both challenging and computationally expensive. The overall goal of this research is to use the emerging Grid infrastructure to realize an autonomic self-optimizing reservoir framework. In this paper, we present a policy-driven peer-to-peer Grid middleware substrate to enable the use of the Simultaneous Perturbation Stochastic Approximation (SPSA) optimization algorithm, coupled with the Integrated Parallel Accurate Reservoir Simulator (IPARS) and an economic model to find the optimal solution for the well placement problem. Wolfgang Bangerth is a postdoctoral research fellow at both the Institute for Computational Engineering and Sciences, and the Institute for Geophyics, at the University of Texas at Austin. He obtained his Ph.D. in applied mathematics from the University of Heidelberg, Germany in 2002. He is the project leader for the deal.II finite element library (http://www.dealii.org). Wolfgang is a member of SIAM, AAAS, and ACM. Hector Klie obtained his Ph.D. degree in Computational Science and Engineering at Rice University, 1996, he completed his Master and undergraduate degrees in Computer Science at the Simon Bolivar University, Venezuela in 1991 and 1989, respectively. Hector Klie's main research interests are in the development of efficient parallel linear and nonlinear solvers and optimization algorithms for large-scale transport and flow of porous media problems. He currently holds the position of Associate Director and Senior Research Associate in the Center for Subsurface Modeling at the Institute of Computational Science and Engineering at The University of Texas at Austin. Dr. Klie is current member of SIAM, SPE and SEG. Vincent Matossian obtained a Masters in applied physics from the French Université Pierre et Marie Curie. Vincent is currently pursuing a Ph.D. degree in distributed systems at the Department of Electrical and Computer Engineering at Rutgers University under the guidance of Manish Parashar. His research interests include information discovery and ad-hoc communication paradigms in decentralized systems. Manish Parashar is Professor of Electrical and Computer Engineering at Rutgers University, where he also is director of the Applied Software Systems Laboratory. He received a BE degree in Electronics and Telecommunications from Bombay University, India and MS and Ph.D. degrees in Computer Engineering from Syracuse University. He has received the Rutgers Board of Trustees Award for Excellence in Research (2004–2005), NSF CAREER Award (1999) and the Enrico Fermi Scholarship from Argonne National Laboratory (1996). His research interests include autonomic computing, parallel & distributed computing (including peer-to-peer and Grid computing), scientific computing, software engineering. He is a senior member of IEEE, a member of the IEEE Computer Society Distinguished Visitor Program (2004–2007), and a member of ACM. Mary Fanett Wheeler obtained her Ph.D. at Rice University in 1971. Her primary research interest is in the numerical solutions of partial differential systems with applications to flow in porous media, geomechanics, surface flow, and parallel computation. Her numerical work includes formulation, analysis and implementation of finite-difference/finite-element discretization schemes for nonlinear, coupled PDE's as well as domain decomposition iterative solution methods. She has directed the Center for Subsurface Modeling, The University of Texas at Austin, since its creation in 1990. Dr. Wheeler is recepient of the Ernest and Virginia Cockrell Chair in Engineering and is Professor in the Department of Aerospace Engineering & Engineering Mechanics and in the Department of Petroleum & Geosystems Engineering of The University of Texas     

Pharmacology,Genomics, and the Evolutionary Biology of Ageing

Aging is a multifold process affected by many genes and thus many biochemical pathways. This conclusion is underscored by the failure to find simple central controls for the aging process during the 20th Century. This situation poses a fundamental challenge to anti-aging medicine: how to develop effective therapies for a genomically complex pathology. We propose such a strategy. As a first step, we recommend the use of model systems in which significant genetic intervention is not proscribed or impractical. Second, we propose that work with such model systems begin with selected lines that have genetic enhancements that allow increased lifespan. Third, genomic methods should be used to identify a number of biochemical pathways for increasing lifespan. Fourth, biochemical pathways that have been identified in model systems would then be available for pharmaceutical development, first in rodents, eventually in a clinical human population. This may seem to be a cumbersome R&D strategy, but starting with human populations or inadequately pre-screened compounds would be unlikely to succeed because of the complexity of the aging problem.     

Concluding synthesis and the future for sustainable goat production

The paper presents an analysis and conclusions of the 9th International Conference on Goats in Mexico. It highlights a very successful conference, the types and extent of subject matter areas that were addressed and their trends. Continuing emphasis on research along disciplinary lines is apparent, in comparison to the more applied links with development issues. It is suggested that future international conferences on goats should give more attention to development aspects concerned with increasing productivity. Emerging issues in the future and looming concerns were identified which emphasise the need for collective efforts to promote the potential future contribution of goats. Policy elements are also important and include: (i) policy through advocacy (i.e., education and empowerment); (ii) gender; investment in research and development (R&D); (iii) direct government action; and (iv) through law (i.e., microcredits and NGO participation). The overriding challenge is to define policies that can improve the livelihoods of small farmers and the landless who own goats, foster greater institutional involvement and investments in target agro-ecosystems, promote increased adaptive research and development involving productivity, enhancing technology application, and vigorous scale up production and post-production systems, linkages and market access. The resolution of these constitutes the challenges for the immediate future.     

SESAME: Scalable, Environment Sensitive Access Management Engine

As computing technology becomes more pervasive and mobile services are deployed, applications will need flexible access control mechanisms. Although lots of researches have been done on access control, these efforts focus on relatively static scenarios where access depends on identity of the subject. They do not address access control issues for pervasive applications where the access privileges of a subject not only depend on its identity but also on its current context and state. In this paper, we present the SESAME dynamic context-aware access control mechanism for pervasive applications. SESAME complements current authorization mechanisms to dynamically grant and adapt permissions to users based on their current context. The underlying dynamic role based access control (DRBAC) model extends the classic role based access control (RBAC). We also present a prototype implementation of SESAME and DRBAC with the Discover computational collaboratory and an experimental evaluation of its overheads. Guangsen Zhang is Ph.D. student in the Department of Electrical and Computer Engineering at Rutgers University. He received his MS from Rutgers University. His research interests include parallel & distributed computing, distributed system security. Manish Parashar is an Associate Professor in the Department of Electrical and Computer Engineering at Rutgers University. His research interests include autonomic computing, parallel & distributed computing, scientific computing, and software engineering.     

Marine scientific research and marine pollution in China

Abstract

In recent years coastal states everywhere in the world have paid attention to the preservation of the marine environment and the conduct of marine scientific research. The scope and nature of China's marine scientific research have been expanded and diversified since the late 1970s because of the growing importance of the ocean for the “Four Modernization “ programs. More and more programs have been designed and executed to find fishing resources, search for offshore oil and gas, promote maritime defense, help alleviate the marine pollution problems, reinforce China's territorial claim in the South China Sea, participate in Antarctic scientific research, and to better understand the whole marine environment. This article first examines China's attitude toward the legal regimes of marine pollution and marine scientific research. It depicts China's marine scientific research activities from the early 1950s. Finally it suggests that more scientific research programs will be designed in support of China's ocean development plans in the future.     

Upcoming meetings

The fall conference season provides abundant opportunities to attend conferences that feature topics relevant to antibody research and development (R&D). Meetings such as these serve critical informational and educational functions, and are key networking opportunities. Locations are spread throughout the world, reflecting the global nature of antibody R&D.     

Nadeshiko revisited: The situation of women in Japanese research and the measures taken to increase their representation

The Japanese government has enacted measures to increase the representation of women in research; the situation is improving but there is still much to do. Subject Categories: S&S: Careers & Training, S&S: History & Philosophy of Science, S&S: Ethics

Japanese parents are understandably proud that their 15‐year‐old boys and girls do equally well in the Programme for International Student Assessment (PISA). In 2018, Japanese girls ranked second and third in Science and Mathematics, respectively, among the 40 participating countries, and Japanese boys ranked first in both subjects (https://data.oecd.org/japan.htm). However, Japanese boys and girls face different expectations and take different career paths as they grow up. In this commentary, we discuss how this affects the situation of female scientists in Japan. We start with the proportion of women in academic research and describe the problems they currently face. We underscore the tremendous measures developed and administered by the Japanese government to increase the participation and proportion of women in research. Finally, we mention an emerging grassroots initiative that is currently being implemented. We suggest that female empowerment may be one of the most promising strategies to improve the situation of women in the Japanese scientific community.