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Adopting an Open-Source Approach to Pharmaceutical Research and Development

10.07.20 | 7 min read | Text by Michael Stebbins & Miranda Bain & Rena Conti & Nicholaos Krenteras & Nicoleta Krenteras & Jaykumar Menon & Bernard Munos

The U.S. pharmaceutical industry conducts over half the world’s research and development (R&D) in pharmaceuticals and accounts for well over $1 trillion in economic output annually. Yet despite the industry’s massive size, there are still no approved therapies for approximately 95% of human diseases—diseases that affect hundreds of millions in the United States and around the world. The disparity between industry inputs and societally valuable outputs can be attributed to two key market failures. First, many medicines and vaccines have high public value but low commercial potential. Most diseases are either rare (afflicting few), rapidly treated (e.g., by antibiotics), and/or predominantly affect the global poor. Therapies for such diseases therefore generate limited revenue streams for pharmaceutical companies. Second, the knowledge required to make many high-value drugs is either underdeveloped or under-shared. Proprietary considerations may prevent holders of key pieces of knowledge from exchanging and integrating information.

To address these market failures and accelerate progress on addressing the overwhelming majority of human diseases, the next administration should launch a new program that takes an open-source approach to pharmaceutical R&D. Just as open-source software has proven a valuable complement to the proprietary systems developed by computer giants, a similar open source approach to pharmaceutical R&D would complement the efforts and activities of the for-profit pharmaceutical sector. An open-source approach to pharmaceutical R&D will provide access to the totality of human knowledge and scientific expertise, enabling the nation to work quickly and cooperatively to generate low-cost advances in areas of great health need.

Challenge and Opportunity 

Approximately 95% of human diseases (~9,500 in number) lack any approved therapies. At the current rate of discovery, it would take 2,000 years to find therapies for all known human diseases. The result is that hundreds of millions of people in the United States and around the world lack medicines and vaccines that are essential to a healthy life.

Simply put, the status quo with respect to drug development has failed. The pharmaceutical industry expends huge amounts of money—often funded with taxpayer dollars—to develop and procure medicines and vaccines, straining national and personal budgets. Moreover, our legacy system of pharmaceutical R&D is unacceptably slow. It now takes 10–20 years for the pharmaceutical industry to develop a single new medicine or vaccine. Pharmaceutical R&D efficiency is declining exponentially: Moore’s Law in reverse. Finally, investment by the existing pharmaceutical industry is driven by profit potential, not societal need. Hence, diseases that afflict many but offer limited revenue streams continue to remain neglected.

It is time for a transformational change in how our nation approaches pharmaceutical R&D. COVID-19 has made it resoundingly clear that we need more medicines, vaccines, and antibody therapies—and we need them to become available fast and made accessible to all. The response to COVID-19 has also demonstrated the value of open R&D in medicine. Thanks largely to unprecedented levels of collaboration, information sharing, and grassroots innovation, our understanding of the disease and the efficacy of potential treatments has advanced at a remarkable pace. Progress on a vaccine for COVID-19 has been record-breaking in comparison with any previous vaccine. Such openness must be further expanded and become the new normal. Right now, most of our nation’s pharmaceutical R&D enterprise is divided among individual labs or companies, with little communication across disciplines or among different research teams. Pharmaceutical R&D is too often conducted secretly, separately, privately, redundantly, and chaotically. And public funds are given to private pharmaceutical companies without guarantees of affordability or openness. We must move instead towards a world in which pharmaceutical R&D is carried out collaboratively, cooperatively, transparently, flexibly, and efficiently. An important step is making key aspects of pharmaceutical R&D—especially publicly funded R&D that is supported or conducted by government—open source.

Plan of Action

The next president should launch a new effort to support an open-source approach to pharmaceutical R&D. Such an approach would differ from conventional approaches and compliment them in four ways: 

As explained in an influential 2006 paper, an open-source approach to pharmaceutical R&D would achieve these goals by integrating six foundational capacities: (i) public and open data and other informational resources; (ii) affordable and widely available tools, algorithms, and models; (iii) advanced computation; (iv) crowdsourcing and crowd commentary; (v) generics and low-cost drug manufacturing; and (vi) the power of sharing, collaboration, and community. 

A government-funded effort to support open-source pharmaceutical R&D could take several forms. This effort could be housed at an independent nonprofit center, or could comprise a new program within the National Institutes of Health (NIH)’s National Center for Advancing Translational Sciences (NCATS). This effort could even exist as a part of a new global hub cofounded by the United States in collaboration with other countries and funders. Indeed, entities from Europe, Africa, Latin America, and South Asia are already working on the concept of open source pharmaceutical R&D. The United States should not be left behind.

However, it is important for the heart of this effort to exist outside of the academic and private sectors and their respective incentive structures. Universities are publication-oriented instead of product-oriented. Private entities are generally profit-seeking, and the consulting firms that often win government contracts typically do not conduct scientific research or create new products, let alone new paradigms. The effort should also be nimble and non-bureaucratic, focused on developing societally beneficial therapies, and characterized by an ethos of creativity, a deep feel for the subject, an open source and community spirit, and working for the public good. Possible implementation options could be recommended by a committee of accomplished innovators who have previously taken ideas from concepts to large-scale results in scientific and social realms.

There are five Initial areas of highest impact for open-source pharmaceutical R&D: (i) off-patent repurposing of existing medicines and vaccines, (ii) discovery of entirely new medicines and vaccines, (iii) creation of one or more scientific-information commons built on public data and resources, (iv) creation of open platforms (e.g., a Github for pharmaceuticals) to grow and connect relevant scientific communities, and (v) expanded artificial intelligence and computational capabilities to advance research. Clinical trial funding would be key, in order to translate research into interventions that have direct health impact. Partial precedents for open source pharmaceutical R&D are numerous and include the NIH NCATS COVID-19 OpenData Portal, the Government of India’s Open Source Drug Discovery Initiative, and a new U.S./Europe/South Asia/Africa/Latin America global hub led by NIH NCATS, the European infrastructure for translational medicine (EATRIS), and the Government of Brazil’s Fiocruz.

The next administration should fund this effort with a minimum budget of $100 million in year one and $200 million in year two. We believe that this funding level, a fraction of the billions per new drug required in traditional industry approaches, would be sufficient to first deliver multiple therapeutics that are affordable and serve areas of great health need, and secondly establish a firm paradigm of open-source pharmaceutical R&D. To be truly transformational, the federal government should eventually increase funding to a few billion dollars per year. This effort would directly improve health. But in addition, expect that it could generate four types of economic returns: (i) direct cash savings, in the form of reduced expenditures on health care and hospitalizations by government, with an ROI of potentially more than 100% annually;1 (ii) some direct revenues, while maintaining openness and affordability; (iii) indirect returns created by improved health; (iv) and other indirect returns.

Federal funding for open-source pharmaceutical R&D should be viewed as an investment with indirect but major returns. By efficiently integrating the capabilities and knowledge of individuals, academics, and industry players in the pharmaceutical sector, open-sourcing R&D will—as already demonstrated in the IT sector—boost markets while delivering materially useful products for all Americans. Initial public investment to create open-source infrastructure for pharmaceutical R&D and unlock new data troves could increase the commercial viability of certain medicine or vaccine opportunities. In turn, this could spur private-capital investment and trigger waves of innovation, similar to ARPANET’s evolution into the Internet. We envision bipartisan support for this powerful approach.

1
See, e.g., Giamarellos-Bourboulis EJ, Tsilika M, Moorlag S, Renieris G, Papadopoulos A, Netea, M, Activate: Randomized Clinical Trial of BCG Vaccination against Infection in the Elderly, Cell, https://doi.org/10.1016/j.cell.2020.08.051 (vaccination of the elderly with the off-patent tuberculosis vaccine BCG reduces the risk of all respiratory infections by 45%). The US spends $14.5 billion yearly on treating such infections (specifically, acute bronchitis, upper respiratory infections, influenza and pneumonia) in the elderly. Agency for Healthcare Research and Quality, Medical Expenditure Panel Survey, 2017. https://meps.ahrq.gov/mepstrends/hc_cond_icd10/. Approximately 65% of those payments, or $9.4 billion, are made by the US government. Reduction of that $9.4 billion by only 10% (as opposed to by 45%) would amount to nearly $1 billion in cash saved annually by the US government, from this single repurposing project alone. For a $100M investment, that amounts to an ROI of over 1,000%.
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