Article: Reboot biomedical R&D in the global public interest

COVID-19 diagnostics, therapeutics, and vaccines are powerful reminders: health technologies can help to shape the way in which societies control disease. Challenges in ensuring global, equitable access to these fruits of biomedical research and development (R&D) during the COVID-19 pandemic have highlighted the urgency of reorienting the system towards the public interest. The first step is a clearer articulation of what R&D in the global public interest is. That is what we seek to do here.

There are four major concerns about biomedical R&D, despite its impressive technological advances amid profound transformations in how knowledge is generated and used. The first is the lack of medicines in areas where market incentives are inadequate to attract private investment, such as for neglected diseases of poverty, bacterial infections and emerging infectious diseases. Second is the slow pace of progress in some areas, such as Alzheimer’s disease. Third is the risk of harm, such as adverse drug reactions. The final concern is restricted access to technologies, caused by high prices, insufficient production or inadequate supply.

These concerns pre-date the emergence of the coronavirus SARS-CoV-2, but the pandemic has underscored the urgency of addressing them. That requires looking beyond just one country or sector.

Biomedical R&D is increasingly global. There is rapid growth in low- and middle-income countries (LMICs) in capacity, investment and networks. And, as medicines markets have globalized, people on every continent pay for health technologies – either out of their own pockets or through public and private medical insurance.

Both public and private interests and investments drive R&D. Research is conducted by public laboratories, universities, private firms, non-profit organizations and health-care facilities (public and private). It is funded by taxpayers, philanthropic foundations, private investors, companies and patients. And it is shaped by public policies and agencies, such as those for intellectual property (IP), regulatory standards, procurement, treatment guidelines and reimbursement.

All of these actors can and should reorient the biomedical R&D system to better serve the global public interest (see ‘Checklist for R&D in the global public interest’). Concretely, that means answering three questions: why do R&D? How should it be done, and for whom?

Why? Priorities
R&D should respond to priority health needs — such as for new antibiotics — as well as responding to intellectual curiosity. However, there is still a lack of systematic approaches. Without them, the market will decide on the basis of the greatest financial return and the lowest risk. The result? Of more than 56,000 candidate products currently under development, 57% are for cancerous tumours. Only 0.5% are for the neglected tropical diseases that affect nearly 2 billion people. Priorities need to be set through processes that are transparent, adaptable and inclusive, not only decided by richer countries. These processes can and must engage citizens, and account for the needs of patients and disadvantaged groups.

How? Ethical, sound, open, fair
All biomedical R&D must be ethical and scientifically sound. International ethics guidelines already exist. However, practices do not always meet these standards. Increased outsourcing to contract-research organizations and the globalization of clinical trials require close oversight to manage risks. Open science, in addition, improves efficiency and accelerates scientific progress, by the timely sharing of research inputs (such as specimens, compound libraries and data sets with appropriate protections), processes (such as protocols, trial designs and cost data) and outputs (including trial results and publications). Current arrangements are inadequate for ensuring such openness, however. For example, the majority of clinical-trial outcomes are not reported on time.

COVID-19 has prompted important steps forward. One is the publication of vaccine trial protocols and large-scale collaboration and data sharing through the WHO Solidarity and UK RECOVERY therapeutics trials. Another is the huge increase in open sharing of genomic sequencing data on SARS-CoV-2 that enables scientists to track how, where and when the virus is changing. Significant changes in rules and incentives are needed to secure the rapid, open sharing of inputs, processes and outputs. For example, it is crucial to govern IP to maximize the societal benefits of knowledge, not merely to generate new inventions.

Some inequities point to this problem. Low and medium-income countries (LMICs) that hosted COVID-19 vaccine trials received fewer doses per capita than did high-income countries. South African researchers publicly shared genomic sequencing data on the Omicron variant of SARS-CoV-2 through the GISAID database, enabling product developers to jump-start potential adaptations to pre-existing drugs and vaccines, but without guarantees that those products will be accessible to South Africa.

Change is feasible, albeit arduous. There are clearly global inequalities. A much broader uptake of open science and benefit sharing are still needed, as is more learning-by-doing and regular exchange. Finally, as COVID-19 has shown, investment in scientific, regulatory and technological capacity must be a higher political priority in countries at all levels of development.

For whom?
Regulators need to collaborate more if technologies are to improve health quickly across different global contexts. This includes finding ways to share or accept data across borders to reduce delays. Currently, regulators do not always require evidence of a therapeutic advance before granting approval, nor are sufficient longer-term studies necessarily conducted after a product is marketed. Instead, they should require concrete improvements, such as increased efficacy, reduced toxicity, fewer adverse reactions or improved patient adherence. And they should ensure that interventions address subpopulations such as children, older people or those who might become pregnant.

In a few areas, affordability and availability are core objectives. The Drugs for Neglected Diseases initiative, for instance, has specified price targets for drugs in advance in design specifications, and has licensed IP to encourage competition between manufacturers. Some COVID-19 R&D projects also aim for global access, such as vaccines largely funded by the Coalition for Epidemic Preparedness Innovations (CEPI). It is crucial to learn from these efforts.

Given the important role that public and philanthropic funders have in all areas of R&D (and ultimately as purchasers of medicines), much more can be done to build conditionalities into health innovation. As well as stipulations about IP, supply and pricing, requirements can include transparency and reinvestment of profits into research. Public-interest research funders could work together on affordability. Technology transfer can enable multiple manufacturers to prevent shortages and secure supply, as for AstraZeneca’s COVID-19 vaccine.

Seize the day
We recognize that reorienting the system towards the public interest is hard. First, nationalism is not easy to align with global health concerns. Taxpayer-financed funders often have industrial, economic and political objectives, as well as health and science ones, such as competitiveness, job creation or boosting exports. Competition between nations, as witnessed in the scramble for COVID-19 vaccine doses, can undermine the willingness to cooperate. Yet international agreements can structure cooperation to meet each country’s needs. International agreements could require contributions of human, financial, cultural and knowledge resources to R&D efforts in return for fair recognition and access to benefits.

Public and private interests are not always aligned. But COVID-19 has demonstrated that public funding and stewardship can reduce the R&D costs and risks borne by the private sector39 — for example, by making affordability or data transparency more feasible. Sharing knowledge or technology is more realistic, albeit not guaranteed, when it has been co-produced by public and private actors. For example, CEPI subsidized R&D and technology transfer for US-based drug firm Novavax’s COVID-19 vaccine. The first regulator-approved doses of this vaccine have been produced in India, with priority supply going to developing countries through the COVAX programme. A creative combination of regulation, incentives and persuasion can align private objectives with the global public interest.

These fundamental governance challenges are not new. Many efforts have been made to address them. These often focus on specific therapeutic areas such as neglected diseases, antibiotics and pandemics, or cover groups of countries or parts of the R&D process (basic research, discovery, translation, development, regulatory review, production, pricing and distribution). Alternatively, they might focus on certain means to achieve specific ends (an international treaty, a global R&D fund, declarations on ethical research or platforms for data sharing).

In this article, we have taken a step back and sought to articulate a more holistic vision. COVID-19 has both exposed the shortcomings of the R&D system and offered concrete examples of how we can and must reorient it to meet the global public interest. The 1948 Universal Declaration of Human Rights recognizes people’s right to “share in scientific advancement and its benefits”. If not now, when?

CHECKLIST FOR R&D IN THE GLOBAL PUBLIC INTEREST
Citizens, researchers, governments, intergovernmental organizations, regulators, funders, industry and universities are all stakeholders in public-interest research and development (R&D). They must collaborate to:

• Prioritize public-health needs through structured, inclusive, transparent and informed processes.
• Require that R&D is ethically conducted and scientifically sound.
• Mandate, incentivize and facilitate rapid, open sharing of inputs, processes and outputs.
• Invest in the long term to strengthen scientific, technological and regulatory capacity across all countries.
• Provide timely access to health technologies that are safe, efficacious and offer therapeutic advances.
• Ensure R&D meets the needs of subpopulations such as children, older people and those who might become pregnant.
• Recognize all contributions fairly.
• Share all benefits equitably.
• Build affordability, availability and suitability into the R&D process.

*Authors: 
Soumya Swaminathan, Chief scientist at the World Health Organization, Geneva, Switzerland.

Bernard Pécoul, Executive director at the Drugs for Neglected Diseases initiative, Geneva, Switzerland.

Hisham Abdullah, Director-general of the Ministry of Health, Malaysia.

Christos Christou, International president of Médecins Sans Frontières, Geneva, Switzerland.

Glenda Gray, President and chief executive of the Medical Research Council, Cape Town, South Africa.

Carel IJsselmuiden, executive director of the Council on Health Research for Development, Geneva, Switzerland, and professor in the School of Applied Human Sciences, University of KwaZulu-Natal, South Africa.

Marie Paule Kieny, Director of research, National Institute of Health and Medical Research (INSERM), Paris, France.

Mariana Mazzucato, Professor in the economics of innovation and public value at University College London (UCL), and founder of the UCL Institute for Innovation and Public Purpose.

Veronika von Messling, Director-general of the Life Sciences Division, Federal Ministry of Education and Research, Bonn, Germany.

Bernhards Ogutu, Chief research officer at the Kenya Medical Research Institute, Nairobi, Kenya.

John Reeder, Director of TDR, the Special Programme for Research and Training in Tropical Diseases, World Health Organization; and director of the Research for Health Department, World Health Organization, Geneva, Switzerland.

John-Arne Røttingen, Ambassador for global health at the Ministry of Foreign Affairs, Oslo, Norway.

Renu Swarup, Former secretary of the Department of Biotechnology, Ministry of Science and Technology, New Delhi, India.

Marcel Tanner, President of the Swiss Academies of Arts and Sciences, Bern; and professor at the Swiss Tropical and Public Health Institute, Basel, Switzerland.

Nísia Trindade Lima, President of the Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.

Michelle Childs, Director of policy advocacy at the Drugs for Neglected Diseases initiative, Geneva, Switzerland.

Alex Harris, Associate director for Government Relations and Strategic Partnerships at Wellcome, London, UK.

Els Torreele, Policy associate at University College London, UK.

Suerie Moon, Co-director of the Global Health Centre and professor of practice, Graduate Institute of International and Development Studies, Geneva, Switzerland.

This article was originally published in its full version in Nature magazine.