Managing risks in drug discovery: reproducibility of published findings

In spite of tremendous advances in biopharmaceutical science and technology, the productivity of pharmaceutical research and development has been steadily declining over the last decades. The reasons for this decline are manifold and range from improved standard of care that is more and more difficult to top to inappropriate management of technical and translational risks along the R&D value chain. In this short review, major types of risks in biopharmaceutical R&D and means to address them will be described. A special focus will be on a risk, i.e., the lack of reproducibility of published information, that has so far not been fully appreciated and systematically analyzed. Measures to improve reproducibility and trust in published information will be discussed.     

How much do the public sector and the private sector contribute to biopharmaceutical R&D?

When examining the prices of new medicines, the question of how much the private and public sectors have contributed to their R&D is often raised. Contributions can be assessed in terms of the investment, authorship of publications, marketing authorizations and intellectual property rights associated with biopharmaceutical R&D. This review of the empirical evidence underlines the complementary and interwoven nature of the private and public sectors in supporting biopharmaceutical R&D. Both sectors invest in and contribute to biopharmaceutical R&D, with the public sector predominantly focusing on basic research and the private sector mainly targeting medicine discovery and development. Public-sector investment generates additional private-sector investment.     

The role of DMPK science in improving pharmaceutical research and development efficiency

The successful regulatory authority approval rate of drug candidates in the drug development pipeline is crucial for determining pharmaceutical research and development (R&D) efficiency. Regulatory authorities include the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Pharmaceutical and Food Safety Bureau Japan (PFSB), among others. Optimal drug metabolism and pharmacokinetics (DMPK) properties influence the progression of a drug candidate from the preclinical to the clinical phase. In this review, we provide a comprehensive assessment of essential concepts, methods, improvements, and challenges in DMPK science and its significance in drug development. This information provides insights into the association of DMPK science with pharmaceutical R&D efficiency.     

Analysis of pharma R&D productivity – a new perspective needed

R&D productivity continues to be the industry’s grand challenge. We analyzed the R&D input, output, and outcome of 16 leading research-based pharmaceutical companies over 20 years (2001–2020). Our analysis shows that pharma companies increased their R&D spending at a compound annual growth rate of 6% (2001–2020) to an average R&D expenditure per company of $6.7 billion (2020). The companies in our investigation launched 251 new drugs representing 46% of all CDER–related FDA approvals in the past 20 years. The average R&D efficiency of big pharma was $6.16 billion total R&D expenditures per new drug. Almost half of the leading companies needed to compensate for their negative R&D productivity through mergers and acquisitions.     

Visual exploration of HTS databases: bridging the gap between chemistry and biology

As pharmaceutical corporations are under pressure to shorten research and development (R&D) cycles for new drugs, novel technologies are being deployed, producing a data explosion in the research environment. Researchers can then become the bottleneck in the R&D cycle when they are unable to analyze data quickly enough. To deliver on the promise of these high-throughput technologies, pharmaceutical R&D must introduce novel decision support systems to support the mantra of R&D decision support: access, analyze and publish.     

R&D efficiency of leading pharmaceutical companies – A 20-year analysis

Comparative analysis of the R&D efficiency of 14 leading pharmaceutical companies for the years 1999–2018 shows that there is a close positive correlation between R&D spending and the two investigated R&D output parameters, approved NMEs and the cumulative impact factor of their publications. In other words, higher R&D investments (input) were associated with higher R&D output. Second, our analyses indicate that there are ‘economies of scale’ (size) in pharmaceutical R&D.     

The promise of crowdfunding to finance R&D of novel diagnostics and therapeutics for incurable diseases

The level of funding available for research and development (R&D) of diagnostics (D) and therapeutics (T) for incurable diseases varies and is not associated with the extent of their disease burden. Crowdfunding is a promising way to increase funding for R&D of D&T for underfunded incurable diseases, such as Alzheimer’s and Parkinson’s disease, which has not been exploited to its full capacity. Investing into efforts to educate patients and researchers about its prospective is a worthwhile endeavor, which could lead to the generation of substantial new capital to finance the development of novel therapeutics for these diseases.     

2020 in review: FDA approvals of new medicines

Amid a global pandemic, the US Food and Drug Administration (FDA) remained relatively active, approving 55novel molecular entities (NMEs) in 2020, the third highest annual rate recorded. Orphan approvals also surged, capturing 60% of NMEs introduced during 2020, as did the number of NMEs approved using a priority review. The pandemic did appear to impact one recent trend, and in a paradoxically encouraging way. Escalating rates of consolidation slowed in 2020, with only 102 companies lost, down by two-thirds over the rate in 2019. This leaves 2000 extant clinical-stage pharmaceutical companies. When limiting this analysis to companies contributing to the research and development (R&D) of an approved drug, eight were lost, leaving 144 extant.     

Democratizing data at Novartis through clinical trial data access

Enabling broad access and usage of clinical trial data within biopharmaceutical companies has historically been impeded by technical, cultural, and policy hurdles. Novartis has attempted to address this comprehensively through a program called data42; here, we explore how a diverse set of enterprise-wide stakeholders formulated a risk-based data access approach to streamline access to anonymized clinical trial data and vastly improved its use by authorized research and development (R&D) associates within the company. The result is that most Novartis clinical trial data requests, from internal associates, can now be automatically approved. The process of developing this framework and its impact on Novartis and the broader industry are explored and discussed.     

Simulating the Impact of Price Regulation on Pharmaceutical Innovation

Background: Because pharmaceutical price controls fall outside the domain of historical experience in the US, standard retrospective statistical analyses of firm- and/or industry-level data are not appropriate for studying the long-run impact of price controls on pharmaceutical innovation. Simulation modeling, however, can be used to address this issue. Objective: To examine, through simulation experiments, the long-run impact of several hypothetical US price-control policies on pharmaceutical innovation; a computer simulation model of pharmaceutical competition and innovation was developed. Study design: Using the most current economic data available, a hypothetical pharmaceutical industry was created. This industry was formulated to reflect many of the relevant aspects of innovation and competition found in today’s global pharmaceutical industry. This industry was then simulated over a 50-year time horizon, under several different price-control scenarios, in order to better understand the quantitative implications price regulation may have on pharmaceutical innovation. Main outcome measures and results: The primary outcome of interest in this study was pharmaceutical innovative output. Because pharmaceutical firms finance their research and development (R&D) with internally generated funds (after-tax sales revenues), price controls in the model have the effect of reducing R&D investment, and therefore innovation. This was measured by two variables: annual innovative productivity (the annual number of drugs produced by the industry) and cumulative innovative productivity (the total number of drugs produced by the industry over the 50-year time horizon studied). Under a system of public-utility type, cost-based price controls, annual innovative productivity in the model fell by between 67 and 73% relative to baseline (the model without price controls); cumulative innovative output fell by between 30 and 37%. Simulation experiments were also run assuming less extreme forms of pharmaceutical price regulation. These experiments produced smaller reductions in innovative output: annual and cumulative innovative productivity fell by between 21 and 49% and 6 and 24%, respectively. Conclusion: The regulation of pharmaceutical prices in the US could have a precipitous effect on pharmaceutical innovation in the long run. Careful consideration must be given to any new policy that advocates imposing controls on pharmaceutical prices. Long run costs — in terms of forgone pharmaceutical innovation — must be weighed against any short-term benefits price regulation may impart.     

Future of drug development: the economics of pharmacogenomics

This report models how the evolving field of pharmacogenomics, the science of using genomic markers to predict drug response, may impact drug development times, attrition rates and costs. While there still remains an abundance of uncertainty around how pharmacogenomics will impact the future landscape of pharmaceutical and biological R&D, we identify several likely outcomes. We conclude pharmacogenomics (as defined in this context) has the potential to significantly reduce both expected drug development costs via higher probabilities of technical success, shorter clinical development times and smaller clinical trials. Our conclusions are, of course, accompanied by numerous caveats.     

Analysis of Manufacturing Costs in Pharmaceutical Companies

In the pharmaceutical industry, costs attributed to manufacturing are a major part of a company’s total expenses. In this paper, trends in various expense and income categories of pharmaceutical companies have been analyzed with particular emphasis on manufacturing costs to gain an insight into their relationships and how they may differ among types of pharmaceutical companies such as brand name, generics, and biotechs. The study includes data published in the annual reports of leading pharmaceutical companies from 1994 to 2005. Twenty-two pharmaceutical companies were selected based on the annual revenues. The set was further divided into three groups: brand names, generics, and biotechs. The analysis shows that, between 1994 and 2005, manufacturing costs (as a percentage of total sales) are different for the three groups of companies listed above. Additionally, each group of companies differs in how savings are leveraged strategically. The data on brand-name pharmaceutical companies also indicate that there is a strong correlation between the reduction of the cost of goods sold (COGS) and the increase in R&D expenditure. This suggests the validity of Vernon’s theory that for brand-name companies, a reduction in COGS will likely have a positive impact on investments in R&D, presumably resulting in much needed innovations and future health benefits for the society.     

基于VAR模型的广东省医药制造业出口贸易关系实证研究

目的:为促进广东省医药制造业出口交货值增加、提高医药制造业出口占比和国际化水平提供参考.方法:选取1998-2019年广东省医药制造业数据,建立向量自回归(VAR)模型,通过协整关系检验、格兰杰因果检验、脉冲响应函数、方差分解等实证研究探讨广东省医药制造业出口贸易活动(出口交货值)、研发投入(研发经费内部支出)、技术创...     

Research and development in drug innovation: reflections from the 2013 bioeconomy conference in China,lessons learned and future perspectives

The enormous progress biotechnology, bioinformatics and nanotechnology made in recent years provides opportunities and scientific framework for development of biomedicine and constitutes a paradigm shift in pharmaceutical R&D and drug innovation. By analyzing the data and related information at R&D level over the past decades, developmental tendency and R&D patterns were summarized. We found that a growing number of biologics in the pipeline of pharma companies with successful products already in the market though, small molecular entities have primarily dominated drug innovation. Additionally, small/medium size companies will continue to play a key role in the development of small molecule drugs and biologics in a multi-channel integrated process. More importantly, modern and effective R&D strategies in biomedicine development to predict and evaluate efficacy and/or safety of 21st century therapeutics are urgently needed. To face new challenges, developmental strategies were proposed, in terms of molecular targeted medicine, generic drugs, new drug delivery system and protein-based drugs. Under the current circumstances, interdisciplinary cooperation mode and policy related to drug innovation in China were deeply discussed as well.KEY WORDS: Bioeconomy, Biomedicine, Drug development, Innovation, Research and development, Strategy and models     

Patent indicators: a window to pharmaceutical market success

Pharmaceutical success in the market is the best reward for pharmaceutical investors undergoing the lengthy, costly and risky process of pharmaceutical Research and Development (R&D). Drugs with high market revenues trigger fierce competition between pharmaceutical enterprises, as is demonstrated by the increasing Mergers & Acquisitions (M&A) cases focusing on seizing the best-selling products. On the other hand, patents, as the best shield for innovative drugs against generic drugs, become a powerful weapon for pharmaceutical enterprises to win the substantial returns generated by market exclusivity. Patents seem to be directly responsible for the commercial success of new medicines. In this context, it is of great significance to find out the empirical associations between pharmaceutical commercial success and patents. By comprehensively analysing 127 drugs marketed in the USA and their 621 American patents, this article identifies the evidence to link various patent indicators with pharmaceutical sales in actual market.     

Pharmacophore-based virtual screening: a review of recent applications

The global pharmaceutical industry is described as facing an ‘innovation crisis’ following the ‘go-go-pharma’ era; in other words, the problem is one of ‘more money and fewer products’. Nevertheless, patients worldwide are awaiting innovative drugs. Therefore, the pharmaceutical industry has a duty to discover and develop novel drugs and medical technologies. Through universal coverage and reform of the patent system, the Japanese pharmaceutical industry has expanded greatly in line with the Japanese economy. However, in terms of scale and R&D investment, the Japanese pharmaceutical firms have lagged behind the foreign multinationals, which have undergone successive mergers and acquisitions. Meanwhile, it is true that several Japanese firms are playing an active role in overseas markets with their own blockbusters. This paper analyses and gives an overview of new trends in Japan’s pharmaceutical industry within the global context.     

Key issues in the pharmaceutical industry: consequences on R&D

Drug discovery is hard, and is becoming progressively harder, with the passage of time! No other field has to handle such an interplay of scientific, fiscal and political factors. The rewards are, nonetheless, worth it: people now live healthier and longer lives than at any point of time in the past. Times are, however, hard for pharmaceutical companies: research and development (R&D) costs are spiralling out of control. New drug approvals, on the other hand, have hit a record low; and the situation is expected to worsen, now that the FDA seems to be exhibiting stricter drug approval standards. Other issues also exacerbate circumstances: huge numbers of blockbuster medicines, which drugmakers rely on to generate their incomes, are coming off patent, and generic competition is intensifying. Both public and investor confidence in the industry have fallen drastically owing to rising drug prices, product safety concerns and late-stage clinical trial failures. This article discusses the key issues that pharmaceutical companies face and in particular the implications they have for the R&D process. I finish by suggesting how drugmakers should change their R&D strategies to succeed.     

创新药物转化研究中ADME的评价

新药研发是一复杂的庞大系统工程, 所涉及的学科门类众多, 研究周期长。而转化研究有助于构建创新药物的基础研究、临床前研究和临床疗效评价直至新药制造和临床应用的系统研发链, 顺畅基础医学和生物学与创新药物研发、临床医学之间的信息和研究关联, 缩短创新药物从实验室到临床应用的研发周期。在新药研发和临床应用过程中, 化合物的体内过程 (吸收、分布、代谢、排泄, ADME) 是其成药性的重要指标。化合物ADME/T性质在创新药物转化研究中发挥重要作用并贯穿研发过程。因此, 在药物设计及新药开发早期就开展药物代谢研究, 有利于提高新药研发的成功率, 降低新药开发的成本, 获得安全、有效的治疗药物。