September 12, 2017 Advisory Board Meeting Summary Minutes

​Department of Health and Human Services
Public Health Service
National Institutes of Health
John E. Fogarty International Center for Advanced Study in the Health Sciences

Eighty-sixth Meeting of the Advisory Board
Minutes of Meeting
September 12, 2017

The Advisory Board met in the Stone House, Building 16, NIH Campus, 9000 Rockville Pike, Rockville, Maryland, at 9:00 a.m., Dr. Roger I. Glass, Chair, presiding.

Members Present
ROGER I. GLASS, M.D., Ph.D., Chair
MICHELE BARRY, M.D., Member
WALDEMAR A. CARLO, M.D., Member
KING HOLMES, Ph.D., M.D., A.B., Member
JOSEPH C. KOLARS, M.D., Member
MICHAEL MERSON, M.D., Member
J. STEPHEN MORRISON, Ph.D., Member
GREG GERMINO, M.D., Ex-officio Member

Also Present
Kristen Weymouth, Executive Secretary
Nalini Anand, FIC
Christopher Austin, NCATS
Geetha Bansal, FIC
Rick Berzon, NIMHD
Seetha Bhagavan, CSR
Kevin Bialy, FIC
Gretchen Birbeck, University of Rochester
Michele Bloch, NCI
Robert Bollinger, Johns Hopkins University
Joel Breman, FIC
Ken Bridbord, FIC
Lauren Brodd, American Association of Immunologists
Stacey Chambers, NINDS
Lois Cohen, NIDCR
Dexter Collins, FIC
Jim Curran, Emory University
J. Christopher Daniel, DOD
Juan Rivera Dommarco, Instituto Nacional de Salud Pública
Robert Einterz, Indiana University
Robert Eiss, FIC
René Etcheberrigaray, CSR
Paul Gaist, OAR
Bob Gillman, JHU
George Herrfurth, FIC
Christine Jessup, FIC
Flora Katz, FIC
Peter Kilmarx, FIC
Perry Kirklan, Purdue University
Vesna Kutlesic, NICHD
Marya Levintova, FIC
George Mensah, NHLBI
Kathy Michels, FIC
Amit Mistry, FIC
John Monahan, Georgetown University
Claudia Moy, NINDS
Jackie Officer, FIC
Shannon Pearce, FIC
Patricia Powell, NIAAA
Leshawndra Price, NHLBI
Beverly Pringle, NIMH
Josh Rosenthal, FIC
Francine Sellers, FIC
Anantha Shekar, Indiana University
Lana Shekim, NIDCD
Leandra Stubbs, NIMH/DAR
Myra Thomas, FIC
Cecile Viboud, FIC
Amber Wilson, OAR
Kimberly, Witherspoon, NICHD
Sanah Zia, NICHD

Director’s Update and Discussion of Current and Planned FIC Activities:

Dr. Roger Glass, Chair of the Fogarty International Center (FIC) Scientific Advisory Board, called the meeting to order at 9:32 a.m. He began by giving an update on what’s happened at Fogarty since the last Advisory Board meeting in May 2017. At the previous meeting, the FIC was in danger of being eliminated under the President’s budget. Since then the Senate and House Appropriations Committees have come out in full support of the National Institutes of Health (NIH) in general and the FIC in particular. He thanked grantees, fellows, alumni, and other interested parties for advocating on behalf of the FIC so successfully. The focus of advocacy is now on the mandated reorganization of the NIH. Dr. Glass had no particular insights to share on that topic at this time.

Dr. Glass turned next to welcome the Board members for 2016, whose approvals had finally come through at the end of August 2017 and whose full membership will become effective shortly. These members are Drs. Gretchen Birbeck, Robert Bollinger, Robert Einterz, and John Monahan.

Dr. Glass highlighted four articles that have recently been published in The American Journal of Tropical Medicine and Hygiene (ASTMH), all of which made arguments for the preservation of the FIC. One of the articles was by a member of the journal’s executive committee, one by former U.S. Representative John Edward Porter, and a biographic piece on John E. Fogarty written by his daughter Mary Fogarty McAndrew.

Microsoft founder Bill Gates visited the NIH campus on June 2, 2017 as part of the annual NIH-Bill & Melinda Gates Foundation conference. Dr. Glass and other NIH representatives spoke with Mr. Gates about vaccines and immunizations, home-based point of care diagnostics, and strategies to promote and maintain African-led biomedical research. The latter projects take the form of the mapping program and the Coalition for African Research and Innovation (CARI) Initiative. Under the current cooperation between the two organizations, Drs. Doug Lowy and John Schiller won a Lasker-DeBakey Award for their trials on the efficacy of single dose HPV vaccinations. Dr. Glass cited it as one of the reverse learning opportunities, because of the tremendous applications in the U.S. as well as in developing countries. Another partnership is the Cookstove Initiative which aims to reduce or eliminate the use of liquid propane gas as indoor cooking fuel in India, Rwanda, Guatemala and Peru.

The Global Alliance for Chronic Disease (GACD) held a meeting in London on June 7, 2017. The current call for GACD is on mental health issues and the treatment of substance abuse disorders in low- and middle-income countries (LMICs). Dr. Pamela Collins, who was the head of the Global Mental Health Research Program in the Office for Research on Disparities and Global Mental Health at National Institute of Mental Health (NIMH), and who has championed this initiative for NIH, has joined the University of Washington (UW) as Director of Global Mental Health. Thanks to the efforts of the Center for Scientific Review (CSR), this upcoming call will be NIH’s first joint peer review. The partners participating in the peer review are the U.K.’s MRC, South Africa’s MRC, Canada’s CIHR, India’s ICMR, Brazil’s FAPESP, and Australia’s NHMRC, among others. The peer review session occurred among the medical research bodies of ten nations in Cape Town, South Africa in early September 2017. Dr. Seetha Bhagavan (CSR) spoke briefly about the experience, and touched on coordinating among different scales used among the various participants. Of the 168 applications, 51 were discussed.

At the end of September NIH will release the 2016 World RePORT data and the dataset will increase in scope to include all direct & indirect awards worldwide. Dr. Glass encouraged those present to look at the new website, which is currently in beta form but will also be rolled out at the end of the month.

On June 5-6, 2017, CGHS held the Science of Stigma Reduction conference. Nalini Anand, CGHS Director, spoke briefly about the conference. There was widespread participation among the Institutes and Centers (ICs) as sponsors of the event. There were two outcomes from the workshop: the first was a planned supplement series of publications that tracks the agenda of the workshop to identify and address the biggest impact research gaps that need the most attention, and the second was the announcement of a new funding opportunity. Another CGHS conference that took place last summer was the Collaborative for Enhancing Emergency Care Research in LMICs workshop that occurred on July 10-11, 2017. The workshop looked at the barriers to conducting research in emergency medical settings and proposed some strategies for overcoming those barriers. There will also be a set of papers that address health systems, clinical, and ethical issues in this domain.

On June 19, 2017 there was a conference in Peru celebrating 15 years of collaboration between the NIH and Peru as a part of the “Fogarty at 50” scientific symposia. One of the aims of the conference was to explore with the Peruvian health organization CONCYTEC, headed by Fabiola Leon-Velarde Servetto, to fund post-docs or overhead administrative costs for NIH investigators who have direct awards studying Peruvian issues. Grant awards in Peru have grown from under 20 in 2001 to over 100 in 2016. Over that period, FIC accounts for 213 of those grants. In looking back to 1997, the NIH Library has done a bibliometric analysis that demonstrates a tenfold rise in Peruvian authored publications, to almost 700 in 2016, with over 6,000 total publications. Dr. Glass pointed out that Peru, because of its culture, climate, and history, is able to study subjects like the effects of altitude on health that are more difficult to study in the U.S. There are a number of diseases, such as cysticercosis and echinococcosis, which are also best studied in Peru. Dr. Glass shared a citation study map demonstrating the citations for different disease areas. Fifty six percent of publications in Peru have a U.S. co-author, i.e. Robert Gilman alone has worked on over 500 publications in Peru. Dr. Glass also shared a graphic of the mentorship network fostered by collaborations between NIH researchers, leading to the development of independent investigators. Much of this work has been driven by the Universidad Peruana Cayetano Heredia, and Dr. Glass singled out Dr. Patricia Garcia as contributing to the ongoing success of these efforts.

The FIC Fellows and Scholars Orientation was held on July 17-21, 2017. About 25 U.S. medical students, 50 post-doctoral fellows, and 20 foreign post-doctoral fellows attended the event. NIH Director Francis Collins came and spoke to the group, along with 14 IC directors and Mary Woolley from Research!America also came and spoke to the group.

Dr. Peter Kilmarx shared his experience at the International AIDS Symposium held on July 23-26, 2017, in Paris, France. Many of the attendees had previous training support or other relationships with FIC and were able to speak to the importance of the Center. Deborah Birx, the President’s Emergency Plan for AIDS Relief (PEPFAR) Administrator, spoke about the relaunch of the Medical Education Partnership Initiative (MEPI) at the event. Dr. Glass highlighted an article in The Lancet, which came out during the conference, arguing that the U.S. should expand its investment in FIC.

The African Forum for Research and Education in Health (AFREhealth) Inaugural Symposium was held August 1-3, 2017 in Accra, Ghana. AFREhealth brought together representatives from over 60 schools of health sciences around Africa. Its purpose is to serve as a convener for various stakeholders to establish partnerships over shared interests. Dr. Joseph Kolars shared his thoughts on the event, highlighting the shift in perspective from MEPI to AFREhealth. He pointed out that the event was African-owned and African-driven, with only a handful of external researchers in attendance.

Dr. Glass spoke briefly about a few additional topics. The National Academy of Medicine is hosting a study committee on the topic of “improving quality of health care globally.” The University of Virginia is dedicating a hall to Dr. Vivian Pinn, who was the sole woman and minority in UVA School of Medicine’s Class of 1967.

The Grand Challenges Annual Meeting will be held on October 1-4, 2017, which will focus on the subject of strengthening African research and development. The event, sponsored in part by the World Economic Forum in Davos, the Wellcome Trust, and the Bill & Melinda Gates Foundation, will encourage academics to perform studies that will establish economic values for strengthening research and development goals on the continent. The ultimate purpose of this will be to make the argument for increased funding to the Africa’s various finance ministries in support of grant sponsorship, as well to the World Bank.

The Conrad N. Hilton Foundation announced the Bangladesh-based Global Health Research Institution, specifically the International Centre for Diarrhoeal Disease Research (ICDDR,B) as the 2017 recipient of the $2 million Hilton Humanitarian Prize. Dr. Glass expressed pride in the success of the ICDDR,B in leading the public health improvements in Bangladesh that have allowed the country to grow from a low to a middle income country.

Dr. Glass went over the upcoming symposia and annual meetings. The American Neurological Association (ANA) will hold an FIC session on October 15-17, 2017, in San Diego, California, where Gretchen Birbeck will be the Presidential Plenary speaker. The American Society of Tropical Medicine and Hygiene will hold FIC program network meetings on November 5-9, 2017, in Baltimore, Maryland. The American Heart Association (AHA) symposium will occur on November 11-15, 2017, in Anaheim, California. The Partnership for Discovery in Global Health will mark 25 years of Kenyan-NIH collaborations with a symposium entitled “Lessons from the Past for the Future” on January 22, 2018. Finally, the American Psychiatric Association will hold its Presidential Symposium on May 9-11, 2018.

Dr. Glass thanked everyone for FIC’s success. He then called for a break before the next presentation.

Global Alliance for Chronic Diseases (GACD) Update:

Dr. René Etcheberrigaray, Deputy Director, CSR, gave an update on the GACD International Collaborative Peer Review. Dr. Etcheberrigaray began by stating that the driving belief throughout this effort is that science is global and that the scientific community benefits from international communication. A joint peer review process also brings together diverse implementation expertise and allows for a better array of quality proposals. While, currently, individual agencies fund the teams involved in this collaborative effort, the ultimate goal is to achieve collaborative funding as well.

He then gave an overview of the review process for research grants at NIH. The CSR assigns applications to the appropriate ICs and/or individual research group study sections. The IC or study section then submits a final statement to the appropriate Institute and corresponding applicants. From there, the Institute engages pertinent advisory councils and boards and, finally, the Institute or Center Director takes final action.

Though this past meeting was NIH’s first participation in a joint peer review process, the GACD has held three other joint peer reviews in the past: one on hypertension in 2011, one on Type 2 diabetes in 2013, and one on lung diseases in 2015. At this latter conference in 2015, the NIH attended in an observational capacity. Dr. Etcheberrigaray opined that there are many more similarities than differences between the GACD review process and the NIH process. He commented that GACD was very accommodating to different governance structures, applying different sets of rules as required. Based on these observations, several ICs including CSR got together in October 2016 and agreed to proceed with NIH participation in the GACD joint peer review process.

Dr. Etcheberrigaray went over some of the unique issues poised by NIH participation. NIH peer review is governed by U.S. federal regulations and cannot be changed except by an act of Congress. Additionally, NIH has a unique scoring system, strong rules regarding confidentiality and conflicts of interest, the need for a designated federal official to authorize the meeting, restricted attendance, and a second level of review by the IC National Advisory Council.

Dr. Bhagavan discussed some more specifics of the review session. She began by discussing the benefits of being able to organize all together rather than being forced to establish granular, individual partnerships. She noted that the most immediate difficulty was that NIH has a different scale, which GACD graciously adopted for the purpose of the review session. The NIH ICs and GACD agencies also agreed to the NIH two-stage editorial review board format in order to comply with NIH rules. Brazil was the sole exception. Of the 176 proposals up for potential review, each agency only brought forward the proposals it considered best so that they could narrow the pool down to 51 proposals. Though the peer review was collaborative, each agency was responsible for determining the best applications to bring forward because funding was not collaborative. For NIH, which was distinct from other GACD participants, this meant that each subject matter expert was assigned 2-6 applications which they then assigned a score that winnowed the total down to 8 applications to bring to the GACD.

Dr. Beverly Pringle, Chief, NIMH Global Mental Health Research Program, discussed some of the science that the GACD mental health call focused on. The ten participating organizations put $18 million into the call and it received the largest response of the four calls held thus far. Mental health issues in general and depression in particular are a huge contributor to the global burden of health care and treatment. Even though mental health treatment dollars see an average 5.3:1 return on investment, there is still a shortage of care. Dr. Pringle explained that this is primarily due to a shortage of caregivers, though studies have been showing that there are a variety of low-cost ways through which this issue can be ameliorated.

Since the problem of implementation remains, NIMH and NIDA initiated RFA-MH-17-650, which aims to support evidence-based, implementation research and to establish a research network. Dr. Pringle explained that NIMH and NIDA are looking for new strategies applicable to high income countries as well as LMICs, new knowledge about mechanisms, new policy and program development, and deeper, broader regional collaborations.

Dr. Glass asked for questions, commenting that this represents a new approach to research within the NIH. Dr. Flora Katz asked whether there was any harmonization among the different grant management methodologies that the different international agencies used. Dr. Bhagavan answered that, yes, some steps were taken to ensure that grants were managed properly and funding was not being awarded in duplicate. Dr. Glass also commented that a group of international grantees were forming through these calls and as a unit present an opportunity for organization, collaboration, and monitoring.

Dr. Gregory Germino asked whether there was alignment among the specific interests or research goals of the participating agencies. Dr. Bhagavan responded that each of the agencies involved submitted applications in the same or similar format as NIH did.

Supplement: Preventing Childhood Obesity in Latin America: An Agenda for Regional Research and Strategic Partnerships:

Ms. Anand, Director, Division of International Science Policy, Planning, and Evaluation (DISPPE) and Director, Center for Global Health Studies (CGHS), gave the presentation. The project, sponsored by CGHS, began with a workshop and culminated in four research articles and an introduction published in obesity reviews in August. Dr. Ben Caballero, from Johns Hopkins University, and Dr. Juan Rivera Dommarco, Director-General of Mexico’s Institutes of Public Health, led the project. Dr. Dommarco provided an overview of the project on behalf of Dr. Caballero and the various authors, supplemented by Drs. Rafael Perez-Escamilla and Michael Pratt.

Childhood obesity is increasing at alarming rates globally and treatment and prevention is lacking. The objective of the project was to stimulate researchers to identify both scientific and cultural or socio-economic factors that contribute to this rise. Among the participants were policy makers, researchers, and representatives from NGOs, the U.S., Latin America, and the NIH. The four research papers the project produced focused on (1) a landscape analysis, (2) research-to-practice components, (3) research priorities, and (4) building research capacity. This data will also be disseminated at the International Conference on Nutrition Symposium in October 2017 in Buenos Aires, Argentina.

For the first paper, the group identified contextual issues. In Latin America, 20% of children are obese, which leads to earlier manifestations of non-communicable diseases. Additionally, Latin Americans face undernutrition as well as excess weight. These nutritional disparities exist at the national, household, and individual level, with the primary drivers being energy-dense, nutrient-poor food and sedentary lifestyles. The surrounding socioeconomic conditions, retail food supply chain, and poorly developed public transit systems also contribute to this.

For the second paper, the group concluded that the research-to-policy effort would be driven by multi-sectorial partnerships aimed towards effective and sustainable policy. In addition, the generation of scientific evidence for the purposes of public policy and evidence-based advocacy need to be conducted in civil society. Also required is legislation and organizations willing to undertake negotiations among all the stakeholders touched by the issue. The paper concluded that scientific evaluation plays a critical and effective role in pushing public policy choices. Specifically, it identified taxes, trans fats bans, front-of-package label requirements, and public transit initiatives in several Latin American countries as successful examples. Dr. Dommarco advocated for changes in environment as well as changes in individual treatment.

For the third paper, the project members identified research gaps. Areas examined included biological challenges to healthy growth, diet and physical activity dynamics, community interventions, and rigorous evaluation of national food and activity programs and regulations. The group ended up with a lengthy list of gaps, defying easy prioritization. There were six primary gaps identified: (1) the need for longitudinal and prospective studies to assess population dynamics across the region; (2) the need to study biologic challenges to assess the correlation between diet and activity with obesity and metabolic outcomes; (3) the need to assess more granular dietary and physical activity patterns; (4) the need for ongoing surveillance and management of initiatives; (5) the need to evaluate the effects of individual behaviors; and (6) the need to evaluate the effectiveness of community and policy interventions. Because Latin American countries are expressing more interest than ever in enacting policy changes in this area, Dr. Dommarco believes there is a tremendous opportunity to study these issues throughout the region.

The fourth and final paper looked at research trends in the region. Obesity is the most frequently explored topic, followed in order by nutrition and physical activity. While there are many observational and cross-sectional studies, there are relatively few cohort and experimental studies. Few countries have made large contributions to build research capacity around this topic, despite the clear need. Brazil, Mexico, and Chile were the standouts among these contributors. Furthermore, research capacity has previously focused on child survival and communicable disease prevention. Capacity must be built in each of the key factors driving childhood obesity as well as in conducting interventions and policy efforts. Regional collaborations, networks, and researcher development pipelines also need to be established.

Citing the four successful challenges outlined in the second paper, Dr. Perez-Escamilla, Director of the Office of Public Health Practice at the Yale School of Public Health, argued that there are many opportunities to fund interventions that can have wide-ranging impacts in Latin America right now. These projects have been successful in a variety of arenas and have been resistant to political pressures that may have impeded previous efforts. Good proximal implementation designs, such as the excise taxes on sugar-sweetened beverages in Mexico, show how policy can persuade others to take similar actions. Dr. Perez-Escamilla also pointed out that there has been an exchange of ideas between the U.S. and Latin American countries where each is learning effective strategies from one another. He specifically cited the work being done in the U.S. on the linkages between genetic heritage and diet, while he also argued that the “open streets” program is much more advanced than similar programs in the U.S. The U.S. has also contributed helpful research on early childhood nutrition and the role it plays in childhood obesity. He finished his remarks by saying that the immigrant population in the U.S. coupled with the country’s research capabilities provides an excellent opportunity for studying the effects of immigration on health.

Dr. Michael Pratt, Professor at the Institute for Public Health, Department of Family Medicine and Public Health at the University of California San Diego, contributed several remarks based on what he had learned through his experience with this study. He explained that one of the driving interests behind choosing obesity as the topic was the high-level of success researchers have achieved through the implementation of public health infrastructure to combat obesity in the U.S. Capacity building cannot be separated from the research projects and priorities of a country because researchers need to be relevant to their context. The flip side of this need is for institutions to become stable sponsors of researchers, so that researchers can establish careers. In keeping with these discoveries, Dr. Pratt discussed how important strong research networks were in order to compensate for various deficiencies that occur on either side of the researcher-institution equation. Dr. Pratt also touched upon the issue of how funding is stratified in countries like Mexico which straddle the boundary between being a middle income and a high income country. On the one hand, cutting off funding tends to negatively affect a country’s ability to build capacity, while on the other hand there are countries in the region that are more in need of these resources. He ended his remarks discussing how developing a core group of elite researchers can serve to build momentum with a relatively small investment.

Dr. Germino shared his response to the study from the perspective of NIDDK, paying special attention to studies that may have applications in Latin America. Obesity is an important research topic in NIDDK, with several studies underway that are examining the linkages between diet and obesity in pregnant women and their children. The Institute is also studying the effects of high sugar intake on mothers and their babies as well as studies on the effectiveness of dietary guidance for parents. There are also studies examining the effectiveness of dietary guidelines in reducing Type 2 diabetes in adolescents. Dr. Germino commented on the excise tax in Mexico, noting that this is an example of a class of interventions that may be easier to execute, and therefore easier to study, in Latin American countries than it would be in America due to political constraints. He promoted some of NIDDK’s current funding announcements as presenting opportunities for potential international collaboration in this space. Dr. Germino argued that the international collaboration would be a good way of establishing the degree of effectiveness of the data on interventions across differing populations.

Dr. Sonia Ortega shared some perspectives from NHLBI that may be relevant to this paper. NHLBI funds the largest longitudinal study of Latinos in the U.S. in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).” Sixteen thousand adults are being followed over a period of years with ancillary studies focusing on their children. The Institute is also sponsoring a number of studies on obesity, with one, in particular, examining obesity in preschool-age children. Another study, the Healthy Communities Study, involves a large Latino population. This study – which is a natural experiment – aims to assess how public policies as well as habits of diet and physical activity affect health across 130 health disparity populations in the U.S. Dr. Ortega also participates in the NIH Obesity Task Force which works closely with NIDDK. She announced that there is a conference in December on this subject called “Pathways to Prevention.” She ended her remarks by promoting the Environmental influences on Child Health Outcomes or ECHO study, which is a trans-NIH program enrolling 50,000 children.

Dr. Glass discussed the work of Dr. Jim Yong Kim, who wants to use stunting as a measure of human capacity because of the correlated effects it has on human development. Dr. Glass proposed conducting cohort studies in Rwanda and Guatemala and other places with high levels of stunting to help discern the mechanisms through which it occurs and identify effective interventions. Dr. Glass also proposed a long term study of the effects of malnutrition and obesity on children and whether there are intersections with cancer or other noncommunicable diseases. Citing his experience in Bangladesh, he also suggested the intersection between nutrition and family planning as another avenue of exploration for researchers interested in this topic.

Dr. Dommarco responded that research in Guatemala has shown that food intake is only one of the contributing factors to stunting, explaining that there are aspects of the microbiome that can also be factors. The effects of the microbiome on obesity represent a very exciting possibility for new research. Dr. Perez-Escamilla also commented on the microbiome subject, saying that there was already some evidence that specific types of microbiomes were contributing factors in this regard, but that it was not clear whether obesity was leading to dysfunctional microbiomes or vice versa. While there’s no doubt that the microbiome affects obesity, there’s insufficient data to measure these effects. Furthermore, there are no international standards for measuring microbiomes, with each lab developing their own model. Dr. Perez-Escamilla commented that, once implemented, he had confidence that good interventions could break the strong epigenetic cycle of obesity between mothers and children. He concluded his comments by adding to Dr. Glass’ list of possible avenues of study the effect obesity has on the social/emotional development of children.

Dr. Robert Bollinger asked the panel to give guidance to FIC members as to what they could do to focus their resources and attentions on this subject. For example, are there high-priority or low-hanging goals that they could address through short-term K awards or similar mechanisms. Dr. Bollinger wondered whether panel members had in mind specific areas where limited funding might drive greater change. Dr. Dommarco said that Dr. Pratt’s suggestions were very relevant here. What would be most useful would be to assist in the establishment of research networks and institutions to build regional research capacity around this subject. Sharing results and sharing methodologies would go a long way towards compensating for limitations in research funding or regional research capacity.

Dr. Pratt echoed Dr. Perez-Escamilla’s earlier point that, from a public policy perspective, many Latin American countries are very advanced compared with the U.S. He argued that NIH and FIC should support studies of these public programs in order to identify viable strategies for applying in the U.S. Dr. Germino expressed his support of these ideas, especially as it relates to FIC’s mission, but cautioned that they must be done in ways that are both fiscally responsible and that will be seen as credible by the research community.

Clinical and Translational Science Awards and Global Health Research

Dr. Glass introduced the CTSAs and Dr. Christopher Austin, Director of the National Center for Advancing Translational Science (NCATS). Dr. Glass emphasized that much of NCATS’ portfolio must be studied internationally as that is where the diseases being studied are located. He added that Europe has an entire body dedicated to conducting clinical trials in sub-Saharan Africa, suggesting clearly that they see this as a priority. Pharmaceutical companies are increasingly turning to clinical research organizations in developing countries to conduct their trials. Moreover, Director Collins has spent much of his career studying progeria which, because of the relatively few cases, has to be studied on a global level.

Dr. Austin began by sharing some of his experience working in a variety of health care settings around the globe. A global health perspective is not just about the U.S. helping developing countries, but also about learning from them. Dr. Austin defined translational science as research that demonstrates how clinical discoveries can be translated into effective interventions that have a demonstrable effect on improving health. Health does not happen in the controlled environment of clinical trials, but rather in real human communities. The field of translational science seeks to understand the mechanisms for affecting the movement from clinical discoveries to effective outcomes, changing it from a phenomenological process to a predictive science.

NCATS is divided into several divisions, each of which involves some degree of global health research. It has a large pre-clinical division which functions as an intramural program but lacks principal investigators and tenure track positions. Each of the projects in this division tackles a piece of clinical research that is stuck in the translational pipeline. About 10% of these projects are global health science projects. Because of the necessity for a broad range of experience in executing these tasks, these divisional teams work in concert with other technical experts.

NCATS has a large presence in the world of rare diseases, many of which are genetic and tend to be orphans in the NIH system. Dr. Austin noted that many of these rare diseases have a high degree of unmet medical need; 95 percent of them have no treatment. In response, NCATS runs the Rare Disease Clinical Research Network, which is made up of 20 consortia of investigators, each of which work on a portion of rare diseases grouped by biological similarities. All of these have an international component because of how uncommon they are.

NCATS also runs the Clinical Translational Science Award program. While the CTSAs began as local clinical research sites within hospitals, by 2007 they shifted to become an institutional resource. There are over 50 CTSAs around the country as a part of the $500 million program. When Dr. Austin became Director of NCATS, he had the idea of expanding the CTSAs to focus on discrete areas of health research rather than discrete locations in the U.S. Congress and the U.S. government have come together to view the CTSAs as a support structure for domestic academic health centers. Dr. Austin supports this view, hoping that the CTSAs can be used in service of the nation’s sick patients wherever they might be.

There’s a corresponding commitment within the CTSA program to service institutional needs. However, as outsiders, the CTSA members are at a disadvantage when determining what the institutional needs are. Congress wants to hear from institutional representatives about where it should be directing funding. Since the fundamental aim of the CTSAs is to derive general principles of translational science from specific examples, NCATS needs to be directed towards which specific examples they should be studying and where in the world those studies should be conducted.

Dr. Glass introduced the next two speakers, Drs. Anantha Shekhar, Associate Vice President of Research for University Clinical Affairs, Indiana University School of Medicine, and Katey Walsh, Clinical Instructor/ Global Health Research Fellow, Dept. of Medicine, Weill Cornell Medical College, Port-au-Prince, Haiti. First, Dr. Shekhar discussed his work with the Indiana Clinical and Translational Sciences Institute 3.0. Indiana has had a CTSA for the past ten years, which they call the Indiana CTSI. It functions as a statewide institution, connecting three universities, a medical school, and a statewide hospital system, as well as number of smaller partner organizations around the state. Dr. Shekhar highlighted their partnership with Moi University in Eldoret, Kenya in particular. The CTSAs are structured similarly across the U.S. with programs for trainees/learners as well as programs for investigators and research programs run out of the hospitals.

The ambitious global health aspect of the CTSA program has been dubbed “reciprocal innovation,” getting at the idea that both sides have something to learn in these global-local relationships. The program leverages the 30 plus years of learning that has occurred between Indiana University and Moi University in the Academic Model Providing Access to Healthcare (AMPATH) program, as well as the more general global health programs at Purdue and Notre Dame. FIC has been the third largest funder of AMPATH over the past ten years, accounting for almost $10 million cumulatively. Dr. Shekhar noted one of the results of this program has been the establishment of a research network among the 15 participating universities.

The basic premise of the global-local program component of the CTSAs is that there are local innovations than can be exported globally in addition to global innovations that can be imported locally. Dr. Shekhar cited localized examples of where this crossover can occur: downtown Indianapolis and Somalia have similar rates of infant mortality. In response, the Indiana Clinical and Translational Sciences Institute (CTSI) founded the WeCare program to reduce infant mortality using methods learned in Kenya. Dr. Debra Litzelman has been the lead PI on this program, training community health workers in downtown Indianapolis to work with young mothers. Key indicators are suggesting success at 18 months into the program and which is expanding out to other community members such as firefighters, paramedics, and police officers. Dr. Shekhar cited another example of leveraging basic science expertise at Indiana University to develop a litmus paper for testing counterfeit HIV drugs, which is a major problem in developing countries. This completes the circle of translation that the CTSA was intended to implement in which a discovery leads to design of a translation, demonstrates its effectiveness, duplicates it in other locales, and ultimately disseminates it among a wider audience.

Dr. Austin asked how these programs are funded. Dr. Shekhar explained that the training portion of the WeCare program was funded through the CTSA, but the implementation was funded through a local hospital. Dr. Waldemar Carlo asked what the typical ratio was of community health workers to mothers, to which Dr. Shekhar responded that there are usually eight to ten mothers per worker. Dr. King Holmes asked if Dr. Shekhar could comment on USAID taking over the AMPATH program and the disaster that followed. Dr. Shekhar said that the disaster had more to do with communication breakdowns between parts of USAID and with decisions made by OMB, but that functionally the program has remained the same on the ground. Dr. Robert Einterz commented that part of the issue has been greater restriction on PEPFAR dollars. He echoed Dr. Shekhar’s point, however, that the program continues to thrive.

Dr. Glass then introduced Dr. Katey Walsh, Cornell and FIC Fellow (2015-2016), to discuss a study concerning the treatment of drug-sensitive tuberculosis in Haiti with the drug nitazoxanide. Dr. Walsh began by giving some background on early bactericidal activity (EBA) trials, which are types of studies that allow for the assessment of the efficacy of antituberculosis agents to occur over 14 days. This particular study looked at repurposing nitazoxanide (NTZ) as an antituberculosis agent. NTZ was initially approved for treatment of giardia and cryptosoridium and is widely available in developing countries. In 2009, researchers discovered that it was effective against microbial tuberculosis in laboratory conditions, with no demonstrable resistance. This data was corroborated by a 2013 clinical trial conducted at the Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO) in Haiti.

The study that they then developed involved 30 participants, 20 of whom would take NTZ for two weeks before initiating standard therapy, and 10 who would only receive standard therapy. Dr. Walsh explained that Haiti was the uniquely ideal place to conduct these tests because of the presence of infrastructure provided by GHESKIO and the familiar working relationships between the New York and Haitian teams. While TB treatment is usually conducted as outpatient treatment, study participants were admitted to ensure the highest level of safety possible. The population was comprised of men and women, 18-65, who are HIV-negative and have TB, which Dr. Walsh said is a very big population in Haiti and very rare in New York. While the study will conclude in November, Dr. Walsh provided some preliminary updates, explaining that the EBA trial model is working very well so far in Haiti, regardless of whether NTZ is working as it is expected to.

Given the presentations by Drs. Shekhar and Walsh, Dr. Glass reiterated Dr. Austin’s earlier question about how those present could imagine using CTSAs for global health. Dr. Joseph Kolars opined that Dr. Walsh’s model could be a great model for CTSAs to follow. He related it to research he had conducted with Peking University Health Science Center as a part of the Joint Institute for Clinical and Translational Research. This Chinese-American collaboration was in the same vein as AMPATH, with an eye towards co-supporting research. He noted, however, that he has struggled to get his CTSA in Michigan onboard with this program. The partnership with Peking University gives Dr. Kolars and his team access to over ten thousand beds and the ability to study a hundred thousand patients. Researchers at Peking University, in return, get to enjoy the knowledge of a distinguished scholar. Dr. Kolars expressed hope that the CTSA momentum would shift in the direction of partnerships like his because it is done so much to broaden the scope of his research. Dr. Glass asked what inhibited Dr. Kolars from calling this partnership a CTSA global-local partnership. Dr. Kolars replied that this project wasn’t mentioned specifically in CTSA funding.

Dr. Carlo added that CTSAs often does not consider global work as a part of their mission. He suggested that highlighting the successes achieved by those CTSAs that do have global components might be a way of combatting this. Dr. Glass asked Dr. Bollinger what the competitive advantage was of working at Moi University as opposed to working in Indiana. Dr. Bollinger responded that the advantages were numerous. The first example he shared was that the AMPATH partnership provided an opportunity for leadership development for both Americans and Kenyans, establishing a relationship that should last for generations. There are also more obvious reasons that there are health issues in Kenya that cannot be easily studied in America, although they exist in America. Dr. Shekhar spoke further from the CTSA perspective, echoing some of Dr. Bollinger’s points. He added that the Kenyan population is extremely genetically diverse which has allowed them to develop a diverse biobank.

Dr. Chris Daniel echoed some of the previous comments from the perspective of the military, in terms of global overseas partnerships, such as those in the Philippines and Thailand. To Dr. Bollinger’s comment about disease and Dr. Shekhar’s about genetic diversity, he added climate and ecosystem as factors that are present and more easily studied elsewhere than in the U.S. for certain cases. From a military perspective, it is important the military doctors are able to take care of troops in a variety of settings worldwide.

Dr. Glass noted that they had not touched upon Dr. Austin’s comments on rare diseases. Dr. Austin replied that oftentimes there are many other issues that take priority over rare diseases in developing countries, where they are seen as luxury healthcare treatments. To date, rare disease treatment in these countries takes the form of communicating lessons learned to parents and patients. He said that the information has been very helpful for him in illuminating the miscommunication between NCATS and the CTSAs around global health.

Dr. Glass armed him with some talking points on that front, reiterating past speakers by arguing that certain research topics, like HIV in children for example, must be studied outside of the U.S. He further cited Dr. Walsh’s study as a million dollar investment that had the potential to deliver wide-ranging, very important results. He also said that there are other platforms for global-local partnerships, such as MEPI, that Dr. Austin could consider. Furthermore, there are examples such as NHLBI which conducts expensive trials in various countries around the world, but calls them clinical trials as opposed to global health. In line with this, Dr. Gilman argued that, ultimately, NCATS is funding translational research, even if some of that research takes place in a global setting. Dr. Bollinger argued that Dr. Austin and NCATS should engage further with FIC on this topic, citing Dr. Gilman’s success in Peru as an example of how successful their approach can be. Dr. Germino suggested to Dr. Austin that CTSAs look at the implementation science principles that can be extracted from global health trials.

Dr. Judy Wasserheit asked Dr. Austin what he sees as the primary question that NCATS is trying to answer in these global health trials. Dr. Austin explained that when he took over NCATS the value of community engagement was not well understood. Within the CTSAs, on the one hand, the researchers have trouble understanding the value of disseminating clinical information, while on the other hand, community engagement advocates have trouble focusing only on the science rather than the public health issues. Now, however, the CTSAs, for the most part, have a stronger understanding of the research aspect of their mission to establish the principles of translational science, though there is still some work to do on that front.

Conclusion:

Dr. Glass made a few closing remarks, citing some further examples of how so-called global health studies contribute to science in general, but also how they augment an understanding of American health care. He asked Dr. Austin to engage in a discussion with his councilmembers and with FIC about how they could best synergize between the two organizations.

Before closing out the meeting, Dr. Glass solicited suggestions for subsequent meeting topics from board members. The next meeting will be on February 12-13, 2018 and the following meeting will be April 30 – May 1, 2018. Dr. Glass thanked everyone involved. He adjourned the meeting at 2:52 p.m.

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