By: Aaron Neal

Most of us are very familiar with the beginnings of INA-RESPOND, either from descriptions during presentations, summaries in publications [1], or first-hand experience. The history usually starts with former Minister of Health Endang’s visit to the NIH campus in Bethesda, Maryland, in 2010. During that visit, then-Minister Endang’s meetings with Dr. Roger Glass, Dr. Anthony Fauci, and others laid the foundation for the Indonesia-U.S. partnership that we all support to this day. However, did you know that government-to-government research partnerships are rare at the NIH and are not the typical way that the NIH works with international scientists?

You may already know that the NIH is the world’s largest funder of biomedical research [2]. Using online tools like the Research Portfolio Online Reporting Tools (RePORT) [3], we can see that in 2022 NIH funded 57,430 research-related awards totaling $32.804 billion dollars. While much of that funding was given to U.S. investigators and institutions, 513 awards totaling over $226 million dollars were given directly to foreign institutions. That may not seem like much in comparison to the overall number of awards given, but direct funding awards are only one way in which the NIH supports international scientific research. In this article, I will highlight the following different ways the NIH works with international scientists: extramural direct awards, extramural indirect awards, intramural collaboration, and government-to-government partnerships.

Before explaining the different types of research support mechanisms used by the NIH, it is helpful to understand two basic terms- intramural and extramural. Intramural research is the research that is conducted by NIH scientists at NIH facilities in the U.S., the majority being located on the main NIH campus in Bethesda, Maryland. Extramural research is the research that is conducted outside of the NIH by non-NIH investigators, the majority being professors, physicians, and scientific professionals at universities, medical schools, and other institutions. Each year, most of the NIH budget actually leaves the NIH in the form of extramural grants, contracts, and cooperative agreements. In 2022, over 84% of the $45.178 billion dollar NIH budget was awarded for extramural research to more than 300,000 researchers at more than 2,500 institutions. Only 10% of the NIH budget went toward supporting the nearly 6,000 investigators in the intramural research program [4].

Given the NIH’s significant financial support of extramural research, it is not surprising that one of the primary ways the NIH works with international scientists is through extramural direct awards. There are many types of extramural awards, each coded with an alpha-numeric identifier like R21 or K99. To easily understand the basics of the extra-mural award system, it is helpful to focus on an example such as the NIH’s flagship research grant, the R01 award. An R01 is a traditional grant that funds investigator-initiated research, usually for a period of up to 5 years. Throughout the year, NIH Institutes and Centers (ICs) release funding opportunity announcements (FOAs) that let the scientific community know that grant funding is available (see an example at [5]). An FOA can be very broad and cover any area of health-related research, or it can be very specific and cover a narrow area of high-priority research. In either case, the research idea and proposal must come from the investigator, which is why the research is termed “investigator-initiated.” In each FOA, the eligibility section specifies if “non-domestic (non-U.S.) Entities (Foreign Institutions)” are eligible to apply. When foreign institutions are eligible, an international scientist can craft their research ideas into a proposal and submit it for funding consideration. If the proposal receives a good score from a panel of expert peer-reviewers, it can be selected for funding by the NIH. This is a very simplified description of a process that can be quite complicated, usually taking at least 8 months from proposal submission deadline to funding [6]. Applying for direct grant funding can also be very competitive, with NIAID only funding the top 12% of R01 proposals it received in 2022 [7]. Investigators, whether in the U.S. or abroad, who have great research ideas, endure the long application process, and are ultimately selected for funding are now recipients of extramural direct awards. The difficult step of actually conducting the research is next, and the NIH is generally hands-off during that process. Each grant recipient is assigned an NIH Program Officer with related subject matter expertise whose job is to help ensure that the grantee is on-track to complete the research that they proposed. Program Officers do not generally help design experiments, troubleshoot assays, analyze primary data, or co-author publications. However, they periodically check-in with grantees and can link them with unique NIH resources, introduce them to other experts in the field, and provide opportunities to get involved in shaping the direction of future research at the NIH and globally. If unforeseen challenges or issues with a grantee’s research arise, their Program Officer can help find ways to solve the problems or re-direct the research so that meaningful results can still be obtained. As you can see, the NIH works with these investigators in a very different way, mostly empowering their independence to drive health-related research forward through their own ideas and scientific interests.

When FOAs state that Foreign Institutions are not eligible, or during times of very high competition for funding, the NIH can work with international scientists through extramural indirect awards. In this instance, the term “indirect” is used when extramural direct awards given to U.S. investigators significantly involve non-U.S. investigators, formally as a “Foreign Component.” For various reasons an NIH FOA may restrict eligibility to U.S. institutions and investigators only. However, the FOA can still permit the inclusion of “Foreign Components.” In these arrangements, a U.S. investigator who is awarded the grant can use the funds to support research in a foreign country or with a foreign investigator. This could mean that the U.S. investigator travels internationally to conduct fieldwork themselves, or more commonly, the U.S. investigator collaborates closely with an international investigator who is supported by funds from the NIH grant. The U.S. grantee still receives support from a Program Officer as described above, but that support also partially extends to the international investigator. Extramural indirect awards are also a great opportunity for international scientists to benefit from NIH funding and resources during times of very high competition for grants. International scientists, particularly from low- and middle-income countries, may be less competitive for NIH grant funding not because of their scientific ideas, but because of a lack of institutional resources, high in-country costs for conducting research, or inexperience with writing NIH-style research proposals. Rather than continuing to be excluded from the NIH scientific enterprise, those investigators can collaborate closely with more competitive U.S. investigators to build experience toward independent funding. A general example of this is NIAID’s recently established Centers for Research in Emerging Infectious Diseases (CREID) Network. The CREID Network FOA [8], which sought very specific research proposals, did not exclude Foreign Institutions from applying. However, the strong competition for the funding resulted in only one Foreign Institution (Institut Pasteur, Paris) being selected for a direct award. If you look at the CREID centers that were funded [9], you will see that all of them collaborate very closely with international investigators in low- and mid-dle-income countries. Many of those relationships grew from longstanding investigator-to-investigator collaborations, and those internation-al scientists are benefiting from extramural indirect awards by gaining access to NIH grant funding, building research capacity, and establishing a competitive track record of collaboration and publication to support their future independent application. Another more familiar example is the IN-SIGHT Network, which receives significant funding from NIAID through a cooperative agreement awarded to the University of Minnesota. Though Dr. Jim Neaton and his team at the University of Minnesota received the award from NIH, international organizations that have participated in IN-SIGHT studies, like INA-RESPOND with ITAC, benefit from the NIH funding.

Similar to extramural indirect awards that rely on investigator-to-investigator collaboration on a research project, NIH intramural scientists can work directly with international scientists through intramural collaboration. The NIH’s approximately 1,200 intramural principal investigators receive core research funding from the NIH, so there are no award codes or competitive grant applications like in the extramural community. Intramural investigators generally have significant freedom in pursuing their cutting-edge research program, allowing them to initiate relevant collaborations anywhere, at any time, at any scale, and for any duration. Investigators in an NIH IC like NIAID frequently collaborate internationally, a good example being Dr. P’ng Loke and his collaboration with Malaysian investigators. Dr. Loke, who is originally from Malaysia, recently joined the NIAID Laboratory of Parasitic Diseases as a Senior Investigator to continue his research on host immunity to helminth infections [10]. After establishing his laboratory, Dr. Loke revived his longstanding collaborations with Universiti Malaya parasitologists, which provides those investigators access to many of the advanced resources at NIAID, including sophisticated instruments and comprehensive core facilities. The collaboration even led to a Universiti Ma-laya professor completing a sabbatical at NIAID and a graduate student completing a postdoctoral fellowship in Dr. Loke’s laboratory. Through this intramural collaboration, Dr. Loke and his international colleagues are conducting significant research, building local scientific capacity, and preparing his colleagues at Universiti Malaya to seek their own NIH extramural direct awards in the near -future.

Unlike Dr. Loke’s individual collaboration with Universiti Malaya parasitologists, the NIH’s government-to-government partnerships are anchored around participating countries and not around collaborating investigators. At the moment, NIAID does not have a government-to-government partnership with Malaysia like it does with Indonesia, Mexico, Liberia, Mali, Guinea, and the Democratic Republic of the Congo. Though that does not prevent Dr. Loke and others from working with Malaysian investigators, the nature of the collaboration is fundamentally different. Government-to-government partnerships are unique in that they are sustained separately from the normal extramural funding system, yet they are not restricted to research that aligns with a specific investigator’s scientific focus like in the intramural research program. All of the government-to-government partnerships that NIAID contributes to grew from discussions at the Minister-level and are supported by a series of nation-to-nation agreements. The absence of pressure from the competitive extra-mural funding system, the joint commitments of support from NIAID and the partner country, and the freedom to explore any scientific area of interest allows the partnerships to conduct research that might be less competitive though still significant in answering locally-relevant questions and building research capacity where it is needed most. The goals of conducting great science that also builds capacity toward independent funding are the same as the extramural and intramural mechanisms described earlier, though many of the constraints on funding, timelines, and reporting are less rigid.

NIH works with international scientists. Much more could be said about each mechanism, but I hope this brief introduction gives you a better perspective on the special nature of government-to-government research partnerships like the one we have with INA-RESPOND. While the Network continues to grow as it has since then-Minister Endang first visited the NIH, I foresee opportunities in the near future to expand the partnership through both extramural and intramural collaboration, all of which will strengthen the Network as it strives toward independent, extramural direct awards.


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