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Japanese pharmaceutical products continue to experience a trade deficit, since import values exceed export values. In drug discovery development, given the pace of technological innovations, there has been a major shift from low-molecular-weight compounds to biomedicine. It is anticipated that industry, academia and government will work more closely together in support of the pharmaceutical industry. Drug discovery requires much time and vast resources before the results can be put to practical use, and evidence suggests that many newly approved drugs derive from university-sourced technology. Pharmaceutical companies keep a close eye on technology evolving in universities. However, some reports state that there is a substantial difference compared to the development costs of the major Japanese pharmaceutical companies. Therefore, the authors hypothesized that there may be some issues hindering industrial-academic partnerships in drug discovery. In order to understand the actual situation and barriers to promoting industrial-academic collaboration, the Japan Pharmaceutical Manufacturers Association (JPMA), Japan Agency for Medical Research and Development (AMED), and the Medical Industry-Academia Collaboration Network (medU-net) Council will work together in issuing questionnaires and conducting an awareness survey. This survey sought the personal opinions of individuals belonging to JPMA and medU-net. Based on the results of this survey, we will introduce the issues related to industrial-academic collaboration and partnerships, and any gaps between industry and academia. Furthermore, we suggest solutions to promoting drug discovery innovation in Japan.

Public financing to incentivise private sector innovation in antimicrobial pharmaceuticals is believed by many to be necessary to defeat growing threats from antimicrobial resistance. Large cash incentives from the public sector are said to be essential to stimulate 'normal' market forces capable of unleashing much-needed innovation. However, there is little evidence to suggest that lack of innovation in drug development is peculiar to antimicrobials or that current deficits in the supply of antimicrobials is due to unique inefficiencies in the antimicrobial market. Neither the history of drug development in general nor of antimicrobial innovation in particular supports economic interventions intended to stimulate private sector supply of new antimicrobials. On the contrary, public underwriting of the private sector, which by definition is compelled to prioritise profit, risks dire consequences for future global health., (© The Author(s) 2018. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We draw from documented characteristics of the biopharmaceutical industry to construct a model where two firms can choose to outsource R&D to an external unit, and/or engage in internal R&D, before competing in a final market. We investigate the distribution of profits among market participants, and the incentives to coordinate outsourcing activities or to integrate R&D and production. Consistent with the empirical evidence, we find that the sign and magnitude of an aggregate measure of direct (inter-firm) and indirect (through the external unit) technological externalities drives the distribution of industry profits, with higher returns to the external unit when involved in development (clinical trials) than in early-stage research (drug discovery). In the latter case, the delinkage of investment incentives from industry value, together with the ability of firms to transfer risks to the external unit, imply a vulnerability of early-stage investors' returns to negative shocks, and the likely abandonment of projects with economic and medical value. We also find that competition in the equity market makes a buyout by one of the two firms more profitable to a research biotech than to a clinical services unit, and can stimulate early-stage investments. However, this long-term incentive can be minimal, notably if the superior efficiency of outsourced operations originates from economies of scope that can hardly be exploited when a firm takes control of the external unit exclusively for itself. R&D outsourcing thus does not always qualify as a relevant pathway to address the declining productivity in innovation that has characterized the industry over several decades., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Failures in the current paradigm for drug development have resulted in soaring research and development costs and reduced numbers of new drug approvals. Over 90% of new drug programs fail, the majority terminated at the level of Phase 2/3 clinical trials, largely because of efficacy failures or unexplained toxicity. A recent workshop brought together members from research institutions, regulatory agencies, industry, academia, and nongovernmental organizations to discuss how existing programs could be better applied to understanding human biology and improving drug discovery. Recommendations include increased emphasis on human relevance, better access and curation of data, and improved interdisciplinary and international collaboration., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Here, we provide a comprehensive study related to the risks of all biopharmaceutical firms going public in the USA between 1996 and 2015. We found 355 firms that met our requirements for being in the sector that focuses on creating drugs for humans. Collectively, these firms spent approximately US$86.9 billion on research and development (R&D) during this time. They also lost approximately US$69.3 billion in combined net income. We also examine the delisting of these firms from a public market, their number of collaborators at the initial public offering (IPO), and estimate the percentage ownership by other biopharmaceutical firms at the IPO., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: To examine how pharmaceutical products that were first marketed between 1950 and 1980 were promoted to physicians through advertisements and briefly review advertising regulations and accuracy of the advertisements in the light of modern knowledge., Methods: We systematically reviewed advertisements promoting drugs for specific therapeutic areas, namely central nervous system disorders (anxiety and sleep disorders, depression, psychoses, and Parkinson's disease), respiratory disorders, cardiovascular disorders, and gastrointestinal disorders. We examined about 800 issues of the British Medical Journal (1950-1980) and about 150 issues of World Medicine (1965-1984)., Results: Advertising material was minimally regulated until the mid-1970s. Many drugs were marketed with little preclinical or clinical knowledge and some with the expectation that prescribers would obtain further data. The peak of advertising occurred in parallel with the surge in the release of novel drugs during the 1960s, but declined markedly after the mid-1970s. Advertisements generally contained little useful prescribing information. The period we investigated saw the release of many novel pharmaceuticals in the therapeutic areas we examined, and many (or their class successors) still play important therapeutic roles, including benzodiazepines, tricyclic antidepressants, phenothiazines, levodopa, selective and non-selective β-adrenoceptor antagonists, thiazide diuretics, β-adrenoceptor agonists, and histamine H 2 receptor antagonists., Conclusions: Advertising pharmaceuticals in the BMJ and World Medicine in 1950-1980 was poorly regulated and often lacked rigour. However, advertisements were gradually modified in the light of increasing clinical pharmacological knowledge, and they reflect an exciting period for the introduction of many drugs that continue to be of benefit today., (© 2018 The British Pharmacological Society.)

Over the years, the pharmaceutical industry has been at the forefront of research and innovation in drug discovery and development. The process of drug discovery extending from preclinical studies to multicentric clinical trials and postmarketing phase is a costly affair running into billions of dollars. On the flip side, not all investigational molecules clear the trial phases and get approved, which puts pressure on the manufacturers to maximize the profit from approved drugs. It is in this key area that the practice of drug promotion plays its role. The World Health Organization defines drug promotion as "all informational and persuasive activities by manufacturers and distributors, the effect of which is to influence the prescription, supply, purchase or use of medicinal drugs". With its humble intent of creating awareness among healthcare professionals and updating their knowledge on recent advances in treatment options, drug promotion has been an important tool, but gradually it has evolved to embrace aggressive marketing strategies and sometimes unethical business and scientific practices where the need for profit-making eclipses commitment to patient care and scientific exploration. In this review, we discuss the evolution of drug promotion practices, the various types, its merits and demerits, the influence of drug promotion on physician prescribing behaviour, the role of regulatory bodies, unethical promotional practices and finally summarize with future directions., (© 2018 The British Pharmacological Society.)

Although external collaboration capability influences the development of personalized medicine, key transactions in the pharmaceutical industry have not been addressed. To explore specific trends in interorganizational transactions and key players, we longitudinally surveyed strategic transactions, comparing them with other advanced medical developments, such as antibody therapy, as controls. We found that the financing deals of start-ups have surged over the past decade, accelerating intellectual property (IP) creation. Our correlation and regression analyses identified determinants of financing deals among alliance deals, acquisition deals, patents, research and development (R&D) licenses, market licenses, and scientific papers. They showed that patents positively correlated with transactions, and that the number of R&D licenses significantly predicted financing deals. This indicates, for the first time, that start-ups and investors lead progress in personalized medicine., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Political momentum and funding for combatting antimicrobial resistance (AMR) continues to build. Numerous major international and national initiatives aimed at financially incentivising the research and development (R&D) of antibiotics have been implemented. However, it remains unclear how to effectively strengthen the current set of incentive programmes to further accelerate antibiotic innovation. Based on a literature review and expert input, this study first identifies and assesses the major international, European Union, US and UK antibiotic R&D funding programmes. These programmes are then evaluated across market and public health criteria necessary for comprehensively improving the antibiotic market. The current set of incentive programmes are an important initial step to improving the economic feasibility of antibiotic development. However, there appears to be a lack of global coordination across all initiatives, which risks duplicating efforts, leaving funding gaps in the value chain and overlooking important AMR goals. This study finds that incentive programmes are overly committed to early-stage push funding of basic science and preclinical research, while there is limited late-stage push funding of clinical development. Moreover, there are almost no pull incentives to facilitate transition of antibiotic products from early clinical phases to commercialisation, focus developer concentration on the highest priority antibiotics and attract large pharmaceutical companies to invest in the market. Finally, it seems that antibiotic sustainability and patient access requirements are poorly integrated into the array of incentive mechanisms.

Importance: A common justification for high cancer drug prices is the sizable research and development (R&D) outlay necessary to bring a drug to the US market. A recent estimate of R&D spending is $2.7 billion (2017 US dollars). However, this analysis lacks transparency and independent replication., Objective: To provide a contemporary estimate of R&D spending to develop cancer drugs., Design, Setting, and Participants: Analysis of US Securities and Exchange Commission filings for drug companies with no drugs on the US market that received approval by the US Food and Drug Administration for a cancer drug from January 1, 2006, through December 31, 2015. Cumulative R&D spending was estimated from initiation of drug development activity to date of approval. Earnings were also identified from the time of approval to the present. The study was conducted from December 10, 2016, to March 2, 2017., Main Outcomes and Measures: Median R&D spending on cancer drug development., Results: Ten companies and drugs were included in this analysis. The 10 companies had a median time to develop a drug of 7.3 years (range, 5.8-15.2 years). Five drugs (50%) received accelerated approval from the US Food and Drug Administration, and 5 (50%) received regular approval. The median cost of drug development was $648.0 million (range, $157.3 million to $1950.8 million). The median cost was $757.4 million (range, $203.6 million to $2601.7 million) for a 7% per annum cost of capital (or opportunity costs) and $793.6 million (range, $219.1 million to $2827.1 million) for a 9% opportunity costs. With a median of 4.0 years (range, 0.8-8.8 years) since approval, the total revenue from sales of these 10 drugs since approval was $67.0 billion compared with total R&D spending of $7.2 billion ($9.1 billion, including 7% opportunity costs)., Conclusions and Relevance: The cost to develop a cancer drug is $648.0 million, a figure significantly lower than prior estimates. The revenue since approval is substantial (median, $1658.4 million; range, $204.1 million to $22 275.0 million). This analysis provides a transparent estimate of R&D spending on cancer drugs and has implications for the current debate on drug pricing.

New alternative market models are needed to incentivize companies to invest in developing new antibacterial drugs. In a previous publication, the Transatlantic Task Force on Antimicrobial Resistance (TATFAR) summarized the key areas of consensus for economic incentives for antibacterial drug development. That work determined that there was substantial agreement on the need for a mixture of push and pull incentives and particularly those that served to delink the revenues from the volumes sold. Pull incentives reward successful development by increasing or ensuring future revenue. Several pull incentives have been proposed that could substantially reward the development of new antibacterial drugs. In this second article authored by representatives of TATFAR, we examine the advantages and disadvantages of different pull incentives for antibacterial drug development. It is TATFAR's hope that this analysis, combined with other related analyses, will provide actionable information that will shape policy makers' thinking on this important issue., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Christopher Bailey (AstraZeneca) and Lee Goodwin (Covance) speak to Sankeetha Nadarajah (Managing Commissioning Editor, Bioanalysis) about the evolution of the Pharma-CRO working relationship between AstraZeneca and Covance.

Most pharmaceutical companies have stopped or have severely limited investments to discover and develop new antibiotics to treat the increasing prevalence of infections caused by multi-drug resistant bacteria, because the return on investment has been mostly negative for antibiotics that received marketing approved in the last few decades. In contrast, a few small companies have taken on this challenge and are developing new antibiotics. This review describes those antibiotics in late-stage clinical development. Most of them belong to existing antibiotic classes and a few with a narrow spectrum of activity are novel compounds directed against novel targets. The reasons for some of the past failures to find new molecules and a path forward to help attract investments to fund discovery of new antibiotics are described., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The combination of growing antimicrobial resistance with a dry pipeline has resulted in infections that can no longer be treated. Specific reasons have led to companies' exit from the antibacterial space, however recent incentives are spurring interest to reinvigorate the pipeline. Areas covered: This article summarizes the available information on the discovery, developmental, and regulatory challenges in antibacterial development that have led to disinterest in the space, as well as ongoing incentives such as public-private partnerships and streamlined pathways to mend these challenges and bring new antibiotics to patients in need. Expert commentary: Clinicians should not only understand the reasons for the decline in antibiotic development that have resulted in the dry pipeline, but also the ongoing initiatives in place to build an appropriate supply. Doing so will result in greater appreciation and prudent use of these life-saving drugs when they become available.

In an Essay, Matthew Todd and colleagues discuss an open source approach to drug development.

This eagle's-eye overview of the drug industry in 2016 provides insight into some of last year's top stories, including disease outbreaks that drove R&D, orphan drug development, pipeline attrition, drug pricing, and the ongoing movement in M&A. We also consider recent political events in the U.S. and U.K. and their potential impact on the industry in the years to come, and take a glimpse into the crystal ball to anticipate the new drugs that may be approved in 2017., (Copyright 2017 Clarivate Analytics.)

The Brazilian pharmaceutical industry is heavily dependent on external sources of inputs, capital, and technology. However, the emergence of technological opportunities and the development of biotechnology and the decline of the patent boom and resulting advances by generic drugs have opened windows of opportunities for the local industry. The article examines the Brazilian industry's innovative behavior vis-à-vis these opportunities, showing that although the industry as a whole invests little in innovation, a few large Brazilian companies have expanded their market share and stepped up their investments in research and development, supported by public policies for innovation. Resumo: A indústria farmacêutica brasileira caracteriza-se pela grande dependência de fontes externas de insumos, capital e tecnologia. O surgimento de oportunidades tecnológicas, associadas ao desenvolvimento da biotecnologia e ao fim do boom das patentes com o consequente avanço dos medicamentos genéricos, entretanto, vem abrindo janelas de oportunidades para a indústria local. Este artigo examina o comportamento inovador da indústria brasileira à luz dessas oportunidades, revelando que, embora o conjunto da indústria mantenha baixos níveis de investimentos em inovação, um pequeno grupo de grandes empresas nacionais vem ampliando sua participação no mercado e intensificando seus investimentos em pesquisa e desenvolvimento, apoiados por políticas públicas de inovação.

Advances in financial engineering are radically reshaping the biomedical marketplace. For instance, new methods of pooling diversified drug development programs by placing them in a special purpose vehicle (SPV) have been proposed to create a securitized cancer megafund allowing for debt and equity participation. In this study, we perform theoretical and numerical simulations that highlight the role of empirical validation of the projects comprising a cancer megafund. We quantify the degree to which the deliberately designed structure of derivatives and investments is key to its liquidity. Research megafunds with comprehensive in silico and laboratory validation protocols and ability to issue both debt, and equity as well as hybrid financial products may enable conservative investors including pension funds and sovereign government funds to profit from unique securitization opportunities. Thus, while hedging investor's longevity risk, such well-validated megafunds will contribute to health, well being and longevity of the global population., Competing Interests: The authors declare that they have no conflicts of interest.

A serious need to spur antibiotic innovation has arisen because of the lack of antibiotics to combat certain conditions and the overuse of other antibiotics leading to greater antibiotic resistance. In response to this need, proposals have been made to Congress to fund antibiotic research through a voucher program for new antibiotics, which would delay generic entry for any drug, even potential blockbuster lifesaving generics. We find this proposal to be inefficient, in part because of the mismatch between the private value of the voucher and the public value of the antibiotic innovation. However, vouchers have the political advantage in the United States of being able to raise sufficient amounts of money without annual appropriations from Congress. We propose that if antibiotic vouchers are to be considered, the design should include dollar and time caps to limit their volatility, sufficient advance notice to protect generic manufacturers, and market-based linkages between the value of the voucher and the value of the antibiotic innovation. We also explore a second option: The federal government could auction vouchers to the highest bidders and use the money to create an antibiotics innovation fund., (Project HOPE—The People-to-People Health Foundation, Inc.)

The high cost of patent-protected brand-name drugs can strain budgets and curb the widespread use of new medicines. An example is the case of direct-acting antiviral drugs for the treatment of hepatitis C. While prices for these drugs have come down in recent months, they still create barriers to treatment. Additionally, prescribing restrictions imposed by insurers put patients at increased risk of medical complications and contribute to transmission of the hepatitis C virus. We propose that the federal government invoke its power under an existing "government patent use" law to reduce excessive prices for important patent-protected medicines. Using this law would permit the government to procure generic versions of patented drugs and in exchange pay the patent-holding companies reasonable royalties to compensate them for research and development. This would allow patients in federal programs, and perhaps beyond, to be treated with inexpensive generic medicines according to clinical need-meaning that many more patients could be reached for no more, and perhaps far less, money than is currently spent. Another benefit would be a reduction in the opportunity for companies to extract monopoly profits that far exceed their risk-adjusted costs of research and development., (Project HOPE—The People-to-People Health Foundation, Inc.)