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Barry Coller is developing a toolkit to designed to help factor global access and affordability into the earliest stages of biomedical discovery. (Credit: Will Ragozzino)

At the height of the COVID pandemic, most people living in high-income countries were already receiving their second vaccine doses, before more than 80 percent of those living in low-income countries had received their first. For Barry S. Coller, head of Rockefeller’s Allen and Frances Adler Laboratory of Blood and Vascular Biology, this disparity reflected a systemic failure. “This was the dataset that got me,” Coller recalls. “Such disparity, when there was the greatest risk of dying. It hit home.”

Coller knew that problems such as these begin long before vaccines ever reach the clinic. For decades, efforts to reduce global health disparities had focused on pricing, distribution, and delivery—only after therapies were already developed and with noteworthy but limited success. What might be accomplished if scientists addressed those barriers much earlier, during the first stages of biomedical discovery?

Initially, Coller wrote a commentary about embedding a commitment to equitable global access to new technologies into the education of basic and translational scientists, in which he reviewed a number of approaches that institutions have taken to achieve this goal. Thereafter, funded in part by the Stavros Niarchos Foundation Institute for Global Infectious Disease Research, Coller set out to explore how researchers could consider issues such as disease burden, licensing, manufacturing, and implementation from the outset, with the goal of making therapies more affordable and accessible in low- and middle-income countries (LMICs) income countries. He and his colleagues—which include senior scholars from The Hastings Center, including Vardit Ravitsky, Karen Maschke, and Gregory Kaebnik—are now developing a toolkit for investigators and educators that could help guide this new approach.

“Millions of people throughout the world, particularly in low- and middle-income countries, do not have access to biomedical innovations that prevent, diagnose, and/or treat a wide range of diseases and disorders,” says Karen J. Maschke, Senior Research Scholar at Hastings. “We designed a Toolkit for basic scientists and early-stage translational researchers who work in U.S. academic institutions that provides guidance about how they can develop their research in ways to help facilitate global access to their biomedical innovations.”

Beginning with equitable outcomes in mind

Economic constraints, patent structures, manufacturing limitations, and distribution challenges all shape who ultimately benefits from biomedical innovation. As a result, LMICs, which are home to nearly 80 percent of the world’s population, shoulder a disproportionate burden of disease yet often lack access to life-saving therapies and technologies.

Addressing these barriers and considering solutions often happens too late in the translational spectrum to make the most sizable impact. Translational research is generally broken into four categories that move biomedical discoveries from bench to bedside. The earliest phases, T0 and T1, involve preclinical research and first-in-human studies, while the later stages consider clinical trials to assess the safety and efficacy of new innovations, healthcare delivery, and healthcare policy. Efforts to improve health equity have historically focused almost entirely on T2 and onward.

“Rather than global access being the province of T3 and T4 investigators,” Coller says, “I wondered what we could do up front to help lower the barriers at the very end.”

Coller is in a unique position to act. As head of The Allen and Frances Adler Laboratory of Blood and Vascular Biology he conducts basic and translational research on bleeding and clotting disorder, and as co-director of the Center for Clinical and Translational Science at Rockefeller, he oversees clinical trials at Rockefeller. Coller has already developed an FDA approved drug and several diagnostic tests, and currently is developing a second drug. As a result, he has spent years learning about the entire translational spectrum. Leveraging this extensive experience and the expertise in bioethics of his Hastings colleagues, the team set out to develop a set of actionable guidelines—ultimately dubbed the Global Access Toolkit—to empower biomedical researchers to begin devising ways to break down global health barriers before even leaving the bench.

A living toolkit

From the beginning, Coller and colleagues knew creating such guidelines would be a complex challenge in its own right. After generating a robust set of recommendations, Coller’s group vetted those ideas in various ways, testing whether they were both ethically grounded and practically feasible. Early versions were piloted within Rockefeller’s Clinical Scholars program, where junior translational researchers were asked to identify barriers that could limit the global reach of their discoveries and consider how those barriers might be addressed during the earliest phases of research design. This draft was then reviewed by a broad network of bioethicists, technology transfer specialists, including Jeanne Farrell, Associate Vice President, Office of Technology Transfer at Rockefeller, vaccine-development experts, physician-scientist educators, and international collaborators affiliated with Rockefeller’s Stavros Niarchos Foundation Institute for Global Infectious Disease Research, completing the first stage of the project.

Broadly, the toolkit will guide researchers through four major stages of innovation: idea conception, patenting and licensing, manufacturing, and dissemination. During idea conception, for instance, the toolkit encourages scientists to consider diseases with the greatest global burden, using measures such as disability-adjusted life years (DALYs), which account for years lived with illness or disability, in addition to mortality. For Coller, this broader perspective is essential. Some diseases may not be fatal, but they can dramatically diminish quality of life, limiting one’s ability to work, care for family, and participate in society. “Some diseases are really horrible, but don’t kill you,” Coller says.

To address patenting and licensing, the toolkit arms researchers with specific questions to bring to university technology transfer offices, while encouraging scientists to pursue entrepreneurship training programs so they can better advocate for equitable access during licensing and commercialization negotiations.

Other sections encourage scientists to engage in “frugal innovation,” designing therapies around manufacturing platforms and materials already common in resource-limited settings. The toolkit highlights the Texas Children’s Hospital COVID vaccine, which relied on established yeast-fermentation technology and Halal-compatible materials to support local manufacturing, reduce the need for refrigeration, and gain cultural acceptance in LMICs.

Finally, to tackle dissemination challenges, the toolkit points to models like the Gates Foundation’s “Global Access” Program and GlaxoSmithKline’s “20 percent Reinvestment Program,” which reinvests profits from least-developed countries into training local frontline healthcare workers to deliver new therapies.

Coller hopes this framework can guide scientists wondering how to achieve broad public health impact, by refocusing their earliest decisions—about what diseases to study, how therapies are manufactured, and how discoveries are shared.

After several more rounds of review, Coller intends to publish a paper describing the toolkit, and to make its first version available online. As a living document, however, Coller envisions the toolkit continuing to evolve alongside changing global-health needs, technologies, and innovative patenting and licensing practices. Future revisions will emphasize co-creation with community and international partners, while Rockefeller’s Clinical Scholars program will study whether exposure to these ideas changes how biomedical scientists approach innovation and global health access.

“We recognize that the toolkit needs to constantly evolve,” Coller says. “It will undergo continuous revisions as people come up with more and more creative ways to address global health access.”