National Institutes of Health
John E. Fogarty International Center for Advanced Study in the Health Sciences
Tuesday, February 12, 2019
The FIC Adviosry Board met in the Conference Room of the Stone House, Building 16, 9000 Rockville Pike, Bethesda, Maryland, at 9:00 a.m., Roger Glass, Chairperson, presiding.
ROGER I. GLASS, MD, PhD, Chair
GRETCHEN L. BIRBECK, MD, MPH, University of Rochester Medical Center
ROBERT BOLLINGER, MD, Johns Hopkins University School of Medicine
MYRON S. COHEN, MD, Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill
JAMES W. CURRAN, MD, MPH, Rollins School of Public Health, Emory University
ROBERT EINTERZ, MD, Indiana University School of Medicine
KING HOLMES, PhD, MD, AB, University of Washington; Harborview Medical Center
JOHN T. MONAHAN, O’Neill Institute for National and Global Health Law, Georgetown University
GBENGA OGEDEGBE, MD, MPH, FACP, Center for Healthful Behavior Change, New York University School of Medicine
GREGORY GERMINO, MD, National Institute of Diabetes and Digestive and Kidney Diseases, NIH (Ex-Officio)
VIKAS KAPIL, DO, MPH, Center for Global Health, Centers for Disease Control and Prevention (Ex-Officio)
Kristen Weymouth, Executive Secretary
Nalini Anand, FIC
John Balbus, NIEHS
Seetha Bhagavan, CSR
Kevin Bialy, FIC
Joel Breman, FIC
Ken Bridbord, FIC
Bruce Butrum, FIC
Amber Cassady, Lewis-Burke Associates, LLC
Dexter Collins, FIC
Anna Ellis, FIC
Robert Eiss, FIC
Paul Gaist, OAR
Dan Gerendasy, NLM
Karen Goraleski, ASTMH
Joshua Gordon, NIMH
Greg Greenwood, NIMH
Christine Jessup, FIC
Flora Katz, FIC
Peter Kilmarx, FIC
Linda Kupfer, FIC
Vesna Kutlesic, NICHD
Christopher Lynch, NIDDK
Tony Mazzaschi, ASPPH
Kathy Michels, FIC
Amit Mistry, FIC
Laura Nyblade, RTI International
Jackie Officer, FIC
Vivian Pinn, FIC
Shana Potash, FIC
Beverly Pringle, NIMH
Ann Puderbaugh, FIC
Josh Rosenthal, FIC
Katrina Serrano, OD/ORWH
Lana Shekim, NIDCD
Marcia Smith, FIC
David Spiro, FIC
Anne Stangl, ICRW
Lisa Stevens, NCI
Leandra Stubbs, NIMH/DAR
Rachel Sturke, FIC
Myra Thomas, FIC
Natalie Tomitch, OAR
Bruce Tromberg, NIBIB
Judy Wasserheit, University of Washington
Darien Weatherspoon, NIDCR
Makeda Williams, ORWH
Mary Wilson, UCSF
Sanah Zia, NICHD
Director's Update and Discussion of Current and Planned FIC Activities
Dr. Roger Glass opened the meeting at 9:06 A.M. and introduced the new members Myron Cohen, Gbenga Ogedegbe, Mary Wilson, Jim Curran and Jacob Gayle. He then shared a brief statement in memoriam of the late Dr. Steve Katz, Director of NIAMS. Joel Breman, senior emeritus scientist at FIC, was named President Elect of the American Society of Tropical Medicine and Hygiene. FIC is updating the World RePORT website, and Dr. Glass requested feedback from members about their usage of and experience with the website. Michael Cheetham will be leading the update and feedback should be sent to him. Dr. Blythe Beecroft updated the Board on the HIV/NCD Mathematical Modeling meeting which was held on December 18-19, 2018 in conjunction with the Lancet Commission. The meeting focused on attaining sustainable development goals (SDGs) and the central role data plays in achieving them.
Dr. Glass has visited a number of African partners since the last meeting. Dr. Glass attended the opening of a new medical school, the University of Global Health Equity, in Rwanda at the end of January 2019. Dr. Francis Collins was not able to join him but was still able to present to the group via video. Dr. Glass outlined some of the work Dr. Anne Sumner, NIDDK, and Dr. Agnes Binagwaho, University of Global Healthy Equity, have been doing to build capacity there. He pointed out that NIH has over 20 grants in Rwanda. Dr. Glass then traveled to Nairobi, Kenya, for the Coalition for African Research and Innovation (CARI) to meet with senior leadership about next steps for the organization. After Kenya, Dr. Glass traveled to Tanzania to sign a partnership agreement for increased overhead funding and additional post-doc training in-country with the Tanzanian National Institute for Medical Research (NIMR) and the Commission for Science and Technology (COSTEC). He highlighted the research of Dr. Julie Makani and her work on sickle cell disease, which is funded by NIH. Dr. Glass then returned to Kenya to meet with the Kenyan Medical Research Institute (KEMRI). NIH has over 200 grants in Kenya. Dr. Glass attended a symposium between a number of the institutes, including Moi University, University of Washington and University of California San Francisco. An article was published in the American Journal of Tropical Medicine and Hygiene on the success of FIC’s mentoring programs and its Fogarty Fellows. Dr. Glass introduced the Board to several of the Fogarty Fellows involved and briefly described some of their work in Kenya. Dr. Glass also visited Moi University, and he discussed the work of NIH grantees there.
Dr. Rachel Sturke spoke about the third annual stakeholder meeting of the Adolescent HIV Prevention & Treatment Implementation Science Alliance (AHISA) in Uganda, February 6-8, 2019. AHISA has 26 teams of NIH-funded researchers working across sub-Saharan Africa. At the meeting, they Explored strategies for stakeholder engagement with policymakers and program implementers, began developing research priorities through concept mapping and conducted implementation science training. Dr. David Spiro spoke about recent publications from FIC’s Division of International Epidemiology and Population Studies (DIEPS). He highlighted in particular a recent paper on influenza and training workshops in Africa and Pakistan as well as the Household Air Pollution Intervention Network (HAPIN) multi-country trial.
As for upcoming events and programs, Dr. Glass spoke about the Consortium of Universities for Global Health (CUGH), coming up on March 8-9, 2019 in Chicago. Dr. Christine Sizemore spoke about her efforts with Dr. Peter Kilmarx to have an NIH staff member assigned to China, which will be overseen by FIC with a number of ICs participation. This staff member will facilitate the interchange of information between the two countries. Dr. Kilmarx shared information on the new African Postdoctoral Training Initiative (APTI), which will support 10 fellows to conduct training in both the U.S. and Africa. Dr. Kilmarx then updated the Board on the National Academies of Sciences, Engineering, and Medicine (NASEM) study, “Crossing the Global Quality Chasm: Improving Health Care Worldwide.” He also discussed the new report, “Money and Microbes,” coming out of the International Vaccine Task Force. The report’s major recommendation focuses on clinical research capacity building as an integral component of pandemic preparedness, coming out of analyses of the Ebola outbreak in West Africa. Dr. Kilmarx described the work of Josh Grubbs who has conducted a meta-analysis of NIH-funded publications since 2009, revealing that 30% of them feature U.S.-foreign research collaborations and 5% are published by foreign researchers only. In terms of countries, China has increased the most over that time, followed by the U.K., Canada, and Germany. China, Brazil, India, and South Africa were all LMICs featured in the top 20 publishers. Ninety percent of FIC’s publications have a foreign co-author. Dr. Robert Bollinger asked if Dr. Kilmarx and Mr. Grubbs have looked at the percentage of the foreign collaborations that were first-authored or last-authored by foreign investigators. Dr. Kilmarx noted Dr. Bollinger’s question and said that he would circle back with an answer.
Dr. Glass informed the Board of upcoming meetings. This year there will be Board Meetings on May 6-7 and on September 5-6. There will be program network meetings on a variety of topics over the next several months and Board members participation is always welcomed.
Program Concepts: GEOHealth
Dr. Christine Jessup, Program Officer, DITR, FIC
Dr. Jessup gave the presentation on the Global Environmental and Occupational Health (GEOHealth) Program. A recent WHO report estimates that in 2012 around 12.6 million deaths globally, representing 23% of all deaths, were attributable to the environment, and that 22% of the global disease burden is due to the environment. The International Labour Organization estimates that more than two million workers die and 317 million people are injured from occupational injuries or illnesses every year. Africa, Southeast Asia, and the Western Pacific bear a disproportionate amount of this burden. Over time, the global disease burden has shifted away from environmentally-attributable infectious diseases to noncommunicable diseases. Researchers estimate that nearly a quarter of this burden could be prevented by reducing environmental risk. Addressing this risk will require a critical mass of scientists trained in data management, occupational health, and an appropriate understanding of the local and political implementation context. LMICs suffer the most from occupational and environmental health risks but lack the scientific capacity to adequately address them.
The GEOHealth Hub Program came into existence as a recalibration of the International Training Environmental and Occupational Health (ITREOH) Program, which ran from 1995 to 2011. While ITREOH was broad, its breadth meant that capacity wasn’t being built in specific locations. GEOHealth began as a successor program in 2012 with 2-year planning grants and was then launched in full in 2015. The program’s objective is to develop hubs or Centers of Excellence (COEs) in various locales worldwide. These hubs will conduct research with multiple funding streams and multiple collaborations, manage datasets, conduct training to build capacity, develop and provide curriculum and outreach materials, and engage policymakers to address environmental and occupational health threats.
FIC is currently doing a process evaluation of this program, but, pending results notwithstanding, the proposal is to continue this program. While the bulk of the research is supported by U01 research awards to LMIC institutions, U2R awards to linked U.S. institutions contribute coordinated research training to LMIC environmental and occupational health researchers. These funding streams will hopefully beget other partnerships with other LMIC institutions as well as with other U.S. institutions. Dr. Jessup went on to outline the seven GEOHealth Hubs awarded in 2015 to Suriname, Peru, Bangladesh, and India as well as regional awards to West Africa, East Africa, and Southeast Asian. Almost two-thirds of the GEOHealth budget is co-funded with partners that include NCI, NIEHS, CDC’s NIOSH, IDRC, and the Global Alliance for Clean Cookstoves.
Since 2015, GEOHealth has published 32 articles, 25 of which involve at least one author from an LMIC. At least 119 graduate and post-doc researchers have been trained by the program. Some of these trainees are faculty at partner institutions who are the lead investigators on U01 award projects. There have been a relatively limited number of cross-network collaborations in the form of trainee exchanges and coordinated research efforts. Dr. Jessup briefly went over the environmental and occupational health research areas supported through the program.
Going forward, the plan for the program is to reissue RFAs to support GEOHealth Hubs with 5-year cooperative agreement awards in the U01 and U2R categories. FIC will continue to look for additional partners and will make adjustments based on the 3-year process evaluation that’s currently underway. Dr. Jessup closed her remarks urging continued support for this program because capacity building requires more time. Dr. John Balbus, NIEHS, also spoke in support of the program and argued for its expansion.
Dr. Gregory Germino asked Dr. Jessup whether there’s been any work done in the GEOHealth Program regarding chronic kidney disease of unknown origin, given that it seems to be clustered in agricultural workers. Dr. Jessup responded that there’s been some preliminary work on that issue in the Southeast Asia Hub, in Thailand. Dr. Glass advocated for NIDDK to get involved in studying that issue.
Dr. Judy Wasserheit asked about the major things that Drs. Jessup and Balbus would like to see done differently and also whether they thought there was enough going on related to the impacts of climate change and environmental impacts. Dr. Jessup replied that climate change ended up being a minor but present area of study in Peru, East Africa, and Suriname. There simply weren’t many grant applications where climate change was a top priority. She elaborated that this was one area she hoped would expand as the program continued. As for major changes, Dr. Jessup said that she would like to see more cross-network collaboration.
Program Concepts: mHealth
Dr. Laura Povlich, Program Officer, DITR, FIC
The mHealth program is also up for renewal. It was approved in 2013 and then first funded in 2014 as a small, 2-year R21 grant program aimed at studying mobile health (mHealth) diagnostics and interventions. FIC wanted to contribute to the evidence base around mHealth while also building capacity in LMICs. The grants also have a tangential goal of bringing in multidisciplinary partnerships. There is a high degree of interest in this area, with applications focusing on a wide array of health issues. Funding is currently in the fifth round as of August 2018, and 55 applications have been funded out of the 462 submitted in the first four rounds.
The program has been successful in bringing new people to the field with 25 of the 55 grants being led by at least one principal investigator (PI) who had not previously received an NIH grant. About 40% of applications had multiple PIs. Forty-nine publications have come out of the program from its first two years, but this number has been increasing over time. Moreover, publications have been featured in unique journals such as Advanced Materials that don’t normally interface with FIC. Dr. Povlich highlighted publications that successfully promoted knowledge generation in the areas of behavior and tech development.
The R21 funding mechanism is problematic because of its short, two-year length. This makes it difficult for investigators to be innovative while also evaluating the results of their research. The program also has difficulty reviewing and evaluating the large number of diverse outcomes. Program officers are figuring out how to narrow the scope to ease this burden while also making the program interesting to researchers. Since the field is more established now, Dr. Povlich expects that it will see repeated use of certain innovations. As evidence for this, Dr. Povlich cited data showing how mHealth projects had been funded through other grants outside of the mHealth program and these projects have a greater focus within mHealth-related research on interventions rather than the development of technology. Since mHealth is being funded more broadly at NIH, FIC is in a unique position to focus on the development of innovative mHealth technologies for LMICs through the mHealth program.
The proposed changes to the program include a phased innovation award (R21/R33). This would maintain the R21 model but would shift it to a milestone-driven model. After the first two years, program officers would evaluate whether the grantees’ milestones had been met. They would then decide whether to transition the research to a 3-year award focused on validation studies. In order to narrow the focus of the program, Dr. Povlich proposed restricting applications to focusing on innovative, new, and emerging technologies, platforms, systems, and analytics. She noted, however, that the feasibility of implementation would still be stressed from the beginning as would the focus on partnerships with LMICs and U.S. institutions.
Dr. Mary Wilson asked how the program disseminates information related to highly valuable interventions. Dr. Povlich responded that because publications are just starting to come out, the program hasn’t fully faced this issue yet. That said, the program does host networking meetings in-person and virtually in order to share information. She also proposed creating webinars for publications as they are issued to inform interested parties.
Dr. Gretchen Birbeck asked Dr. Povlich to identify the best ICs for following up on the R21 research that had been done and also to elaborate on the R33 model. Dr. Povlich answered that some PIs have found success applying for follow-up R01s from the same institute that initially funded the R21. She noted that there has been some trouble in cases where there’s not a clear IC to associate with the research and FIC has funded the initial grant. She added that the R33s would be submitted and approved in tandem with the R21 applications and that whichever IC funded the R21 would fund the R33 as well.
Dr. Gbenga Ogdegbe noted that many of these PIs were from the U.S. and argued that, in service of capacity building, LMICs need to be actively engaged in this process. Dr. Povlich agreed but noted that while they do accept applications from foreign institutions, there simply haven’t been that many applications submitted.
Dr. Wasserheit asked about how the program was considering encouraging the next phase of innovation. Dr. Povlich said that the language in the RFA would be crucial to spurring innovative applications and cited gaming and artificial intelligence as two areas that showed promise. Dr. Wasserheit suggested that the program think about ethics questions if they were going that route.
Dr. Bollinger echoed Dr. Wilson’s comments and encouraged the program to work with stakeholders like policymakers and companies on mHealth applications, especially in regions like sub-Saharan Africa. Dr. James Curran elaborated on Dr. Bollinger’s comments, discussing the relationship between mHealth and implementation science. Dr. Povlich agreed and noted that FIC has funded some joint mHealth-implementation science research.
Program Concepts: Global Infectious Disease (GID) Planning Grant (D71)
Dr. Barbara Sina, Deputy Director, DITR, FIC
Dr. Sina proposed a modification to the GID D71 grant. Current D71 planning grants are limited to one year and cover such activities as needs assessments, meetings with U.S. collaborators and faculty, and writing D43 applications. Application data has revealed that few of these D71 grants resulted in successful GID D43 applications.
In light of this, Dr. Sina outlined her proposal, adding more time and more money to these grants. The money would go to additional leadership training for PIs and faculty, and the time would allow them to develop more thoughtful, innovative approaches. She expects that this will result in more substantive D71 proposals with more consistent application reviews as well as more innovative and more thoroughly planned D43 applications. She also noted that because of the training and the resource gathering focus of the new D71s, there would be an increase in an institution’s research training capacity regardless of whether a successful D43 application was generated.
Dr. Ogdegbe wondered if a deeper exploration of why the D71s have not been successful was necessary. He agreed that adding Dr. Sina’s proposed elements would strengthen the D71 grant process, but he doubted whether it would result in more successful D43s. Dr. Sina responded that, looking at the data from LMICs, investigators who don’t pursue the D71 planning grant are more successful with D43s than those that do. On the other hand, organizations without much training capacity often apply for D71s. In light of that, Dr. Ogdegbe asked about whether an institution’s low level of commitment had anything to do with the low success rate of D71s. Dr. Sina responded that the burden of obtaining that commitment was on the applicants.
Dr. Curran noted that in a previous discussion, several people had commented that even successful D43s would have been strengthened by having a D71 beforehand. Consequently, he opined that these programs should be more closely married so that unsuccessful D43s are re-routed through or encouraged to apply for D71s. Dr. Sina replied that it would be very difficult to convert them to D71s because the applicants would have to choose to apply and presumably have a rationale for pursuing D71s instead of D43s.
The Science of Stigma Reduction: New Directions for Research to Improve Health
Dr. Gretchen Birbeck, University of Rochester
Nalini Anand, Director of FIC’s Center for Global Health Studies, introduced the speakers and the topic. A special issue of BMC Medicine will be published that will include around nine articles on the science of stigma. Dr. Birbeck then gave an overview of FIC’s research on stigma which began in 2001. One of her first memorable encounters with stigma occurred while conducting research in rural Zambia with a vulnerable, stigmatized population. NIH began to study the science of stigma through its Challenge Awards, given out between 2001 and 2008. Over that time, HIV-related interventions exploded, while other stigma-related interventions lagged behind that progress. Nevertheless, more and more studies emerged focusing on stigmas as sub-aims during and following the Challenge Awards.
In 2017, the Science of Stigma Reduction: New Directions for Research to Improve Health meeting took place at NIH. The consensus that came out of this meeting was that the science had matured enough that researchers had to be focused on scalable stigma reduction interventions. This agreement spurred the creation of a unified framework and common approach, which will be part of the BMC Medicine special issue. BMC Medicine is the flagship medical journal of the BMC series and has an impact factor of nine. All contributions to this issue underwent a very rigorous peer-review process. Among the topics included in the issue, intersectional stigma reduction will figure prominently.
Dr. Anne Stangl, Senior Behavioral Scientist, International Center for Research on Women (ICRW)
Dr. Stangl walked the Board through the Health Stigma and Discrimination Framework. Even though many stigmas share common traits, studying the stigmas of specific diseases has led to the creation of theoretical silos. Consequently, stigma research has focused primarily on the psychological pathways of stigma rather than the social or structural pathways and the efficacy of multi-level interventions was curtailed. The health stigma and discrimination framework was developed in response to this issue. Built on the previously published stigma reduction articles in addition to the collective practical experiences of researchers, its intent is to give unified conceptual organization to diverse lines of research.
Stigma varies across low, middle, and high-income countries as it unfolds across the socioecological spectrum. The framework is broken down into four constituent parts: (1) Drivers & Facilitators, (2) Stigma ‘Marking,’ (3) Manifestations, and (4) Outcomes. Certain socioecological factors promote stigmatization. Drivers, which range from fear of infection to fear of social judgment, are generally considered negative. Facilitators, which range from cultural norms to occupational safety standards, can be either positive or negative. These factors dictate how the stigma is ‘marked’ or designated. Intersecting stigmas occur when people are marked with multiple stigmas. Once these stigmas are established, they manifest in a variety of ways. These manifestations can be social, legal, anticipatory, and internalized discrimination and includes the discrimination faced by secondary relatives such as family, friends, and caregivers. Stigma markings also manifest in a variety of practices, meant to enforce them. This system results in an array of outcomes, including limited access to justice as well as a limited right to health care. It also influences laws and policies more generally.
The new framework eliminates the distinction between the stigmatized and the stigmatizer. We all participate in and suffer from stigmas in different parts of our lives. Previous frameworks that enforced this dichotomy enabled people to set others apart from the norm and thereby continued the stigmatization process. This framework moves away from a psychological model which considers stigma as a thing one individual places on another to a more wide-ranging and structural model that includes the role of social organizations and institutions. The framework also differentiates outcomes for affected populations from outcomes for these institutions. The hope is that this framework will provide standardization to study stigma reduction interventions. By clarifying the actors involved and their relationships, it will also enable researchers to better identify possible foci.
Dr. Stangl gave an overview of how the framework could be applied to leprosy and mental health. Leprosy is driven by fear of contagion as well as fear of broken social taboos and is facilitated by socioeconomic status. Gender and ethnic backgrounds such as caste can be intersecting stigmas. These stigmas manifest in a “spoiled identity” concept for affected persons and may cause them to conceal their condition. Concealment causes stress in the affected person, however, and delays treatment, which in turn increases the severity of the disorder. At the organizational level, the stigma around working in leprosy services may lead to increased turnover and may also ultimately lead to greater transmission of the bacilli in the community. As a second example, mental health is often stigmatized as being uncontrollable or dangerous. Race and gender intersect with mental health stigmas. Negative public attitudes and internalization of the stigma promote its existence. As a result, people with mental health issues tend to have more trouble holding jobs and realizing their potential. Enactment of protective laws such as the Americans with Disabilities Act has brought some amelioration to the stigma.
Dr. Laura Nyblade, Fellow, Health Policy, RTI International
Dr. Nyblade has been passionately studying stigmas for the last twenty years, primarily in relation to HIV. Her recent research has focused on stigma in health care facilities because stigma in this area has cascading effects on health. Studies have documented such stigma in facilities around the world, both by clinical and non-clinical staff. While there is great potential for interventions to simultaneously reduce stigma, there are relatively few practical resources for addressing and reducing stigmas. Stigma reduction in health facilities is rarely part of the healthcare delivery routine, and workers are infrequently trained on it as well.
One of the barriers to implementing stigma reduction is empowering people by suggesting clear and immediately actionable proposals. Dr. Nyblade used the example of fear of HIV transmission which is still fairly common even among doctors. Providing information about how HIV transmission functions effectively and easily reduces this stigma. Creating awareness of stigmas promotes improved health outcomes.
Dr. Nyblade’s program focused on seven commonly stigmatized health conditions and examined various interventions proposed to reduce the stigmas surrounding them. It also assessed gaps in the literature as well as potential synergies for joint responses. Forty-two articles met the inclusion criteria covering three of the seven health conditions, HIV, mental illness, and substance abuse. No articles on tuberculosis, diabetes, cancer, or leprosy met the inclusion criteria. Dr. Nyblade provided a caveat regarding tuberculosis, suggesting articles that would meet the criteria simply have not been published yet. Interventions for these conditions were distributed across the globe but primarily focused on high-income countries in the Americas. Researchers noted that there were several distinct, common methods that arose from their analysis including provision of information, skills-building activities, participatory learning approaches, contact strategies, empowerment of clients to demand non-stigmatized care, and structural or policy change approaches. Dr. Nyblade then provided a breakdown of these 42 articles by illness and by method. She noted some gaps in the literature related to health facilities, including intersectional stigma research, interventions that target non-clinical staff in addition to clinical staff, and interventions that have a multi-level focus. Joint stigma reduction research would create economies of scale and increase the efficacy of interventions.
Ms. Anand noted that this project has been a close collaboration with the National Institute for Mental Health (NIMH). Dr. Ogdegbe commented that these presentations clearly support the notion that these interventions need to include multiple disorders as well as multiple disciplines. He also opined that, in non-Western cultures and countries, interventions will need to address the informal places, outside of healthcare settings, such as mosques and churches. Dr. Greg Greenwood, Program Officer, Office of AIDS Research (OAR), thanked the presenters and discussed some of the impacts the program’s findings have had on his office’s work, emphasizing the importance of an intersectional approach to stigma reduction.
Dr. Curran expressed sympathies with Dr. Ogdegbe’s comments, pointing out that entrenched prejudices against race and sexual orientation have exacerbated the stigma around HIV, but that these prejudices are not the same as stigma. Among other examples, he cited not expanding Medicaid in the southern U.S. as an example of the role institutional stigmas play in amplifying the negative impacts of stigmas. This is part of a larger difficulty that affected individuals face, feeling like society at large is against them.
Dr. Myron Cohen asked about the 90-90-90 program and how the new framework has affected analysis of it. Drs. Nyblade and Birbeck suggested that Dr. Cohen join the panels in March. Dr. Nyblade went on to explain that there is a significant body of research applying the new framework to each part of the 90-90-90 program. She also responded to Drs. Ogdegbe and Curran, explaining that there has been significant research on stigma reduction outside of the health care setting, clarifying that her presentation was intended to discuss a portion of the larger issue. Moreover, health care workers, because they occupy leadership positions in their communities, tend to serve as excellent focal points for disseminating information about stigma reduction.
Dr. Judy Wasserheit asked about the absence of a community-level intervention in Dr. Stangl’s framework. Dr. Stangl shared that she believed one of the challenges in developing such an intervention is coming up with something that is actionable and concise. Institutional and community-level interventions are notoriously difficult to construct, whereas individuals who sit in positions of power at these levels can be affected. Mr. John Monahan echoed Dr. Curran’s comments but also agreed that even if laws and public policies were changed, entrenched individual attitudes would remain. He also expressed hope that strategies for individual engagement would come out of this research. Dr. Nyblade replied that a lot of research has been conducted on that subject and that they have discovered that engagement has to be participatory and non-threatening and has to come from peers. Dr. Stangl added that some of these techniques have been used with community leaders such as imams in Afghanistan, who promulgate some of this information during Friday prayers.
Update from the National Institute of Mental Health (NIMH)
Dr. Joshua Gordon, Director, NIMH
Due to some of the members’ time constraints, a joint question and answer period for both Drs. Gordon and Bruce Tromberg will follow their presentations.
Dr. Gordon gave an update on NIMH’s integrative approach to global mental health research. While NIMH does some global work with HIV, the majority of its focus is on behavioral approaches to adherence both in terms of treatment and prevention. The focus of the talk, however, was on mental illness. As measured by disability-adjusted life years (DALYs), mental and substance abuse disorders rank in the top ten of the global contributors to DALYs, though Dr. Gordon suspects that that number is an underrepresentation.
Shortly after Dr. Francis Collins took the helm at NIH, Dr. Pamela Collins was appointed head of NIMH’s global health division. She began her tenure at NIMH by establishing global hubs with the aim of conducting research and building capacity. These hubs functioned through collaboration across disciplines and with in-country researchers as well as end-users of the research. Initially, there were five hubs, each of which was oriented towards the mental health challenges specific to its context. One of the early conclusions from these hubs was that mental health issues affected treatment of chronic diseases. This led to the creation of joint interventions that took into account both mental and physical aspects of treatment. Because these joint interventions often took place in lower resource settings, a solution was developed that involved training non-mental health professionals to treat mental health issues.
After these research hubs, Dr. Pamela Collins and her team looked to scale-up the global hubs and integrate new ones as well. These hubs were focused on implementation science research. Implementation science has been one of NIMH’s strengths, and the goal at this stage was to conduct research that could be applied domestically. Many of these hubs included integrated data management systems and incorporated multilateral organization advisory boards. The hubs were also brought together annually to share resources, especially regarding capacity building.
Dr. Gordon went over an example of the integrative hub model at work in Nepal, where lay workers were trained to identify neuropsychiatric disorders in their patients. The grants for this training came from the WHO, but the nonprofit delivering the care was also funded from American collaborators. The system recycles service users back into the training modules to promote the training further. While the data of this intervention is not yet published, Dr. Gordon affirmed that it had extremely positive results. He also discussed another example of HIV and mental illness in Eldoret, Kenya, where pedal-powered pumps provided to farmers reduced stigma and positively affected HIV outcomes. The clinic in Eldoret has an electronic medical record system so it participates in worldwide data collection and dissemination.
NIMH’s Global Mental Health Research division is embedded within its HIV division in order to maximize the synergy between the HIV and global mental health efforts. NIMH is also expanding its global mental health research efforts to include translational and discovery-based studies in its global portfolio, especially surrounding genomics in people of African descent, inflammatory biomarkers, and psychosis. The 10th Annual Global Mental Health Conference will be held on April 8-9, 2019.
Development of Wearable and Bedside Biophotonics for Personalized Health
Dr. Bruce Tromberg, Director, National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Dr. Tromberg comes to present to the Board only 27 days into his tenure as the Director of NIBIB. Prior to this position, Dr. Tromberg directed the Beckman Laser Institute and Medical Clinic at UC Irvine. The Institute is active in clinical and operating room research, translational research, basic science and technology, philanthropy, and commercialization. It had raised over $70 million in intellectual property royalty revenue by the end of his time there. For 20 years, Dr. Tromberg ran a P41 research center, which was a joint funding venture between NIBIB and NIGMS. This funding is a tremendous driver of technological development, directly responsible for twice as many patents as the next closest NIH institute and more than twice as many as any other federal agency. Dr. Tromberg thanked Dr. Jill Heemskerk and Dr. David George for transitioning him into NIBIB as well as Dr. Roderic Pettigrew for initially inspiring his work with NIBIB.
NIBIB was created in December 2000 and had $280 million dollars across 600 awards by 2002. That number has increased at about 2% per year to $380 million across nearly 700 awards. NIBIB is the only IC that directly supports the engineering and physical science disciplines in biology and medicine. Dr. Tromberg emphasized the importance of human health in engineering programs across the country, with nearly 30,000 undergraduate students involved in biomedical engineering nationwide. This represents an opportunity to drive both human and economic health. Since NIBIB’s inception in 2000, NIH’s grants to biomedical engineering and engineering departments have grown sevenfold. NIBIB has driven this increase, going from 0.6% to 1.9% of the NIH budget. This funding has allowed engineers to consider problems they hadn’t been able to before.
The core of NIBIB’s vision for health is data science and mathematical modeling. Four areas interface with this core capability, including biochemistry; small, physical instrumentation such as wearables; large physical instruments such as MRI machines; and therapeutics including energy- and light-based therapies. While medicine formerly relied on static biological snapshots, the future of medicine will rely on continuous and dynamic monitoring. This is the digital health revolution. That this is the future has been substantiated by the numerous innovations in the field as well as the $27 billion in venture capital that has been invested in digital health since the Affordable Care Act in 2011. The goal of the digital health enterprise is to reduce cost, improve access, and improve outcomes – while also making money for the investors. Global health efforts can leverage this capital and these advanced technologies.
Dr. Tromberg used biophotonics to illustrate these points. Lasers have become cheap and commonplace accessories in consumer and medical devices. Biophotonics, a subset of medical applications for lasers, is a $70 billion industry, annually, and is divided into two primary realms, diagnostics and therapeutics. Therapeutic applications are commonly used for surgeries while diagnostics use biophotonics for imaging and spectroscopy. Consumer devices are converging with medical devices, and this presents new opportunities for biophotonic applications.
Dr. Tromberg gave an overview of a number of innovations utilizing biophotonics. The varying ways in which varying wavelengths of light reflect off of and through tissues can reveal information about the content and structure of those tissues and therefore information can be revealed by flashing light through tissue. Another example uses dynamic cooling and heating lasers to treat disorders such as port wine stains or vascular malformations, all while imaging it in real time. A third example, Doppler optical coherence tomography (OCT) can be used for retinal angiography and blood flow. As compared with some alternative techniques, OCT uses no exogenous contrast agents and is therefore less painful and invasive while also being more accurate. A fourth example called multi-photon microscopy uses femtosecond lasers to interrogate what’s going on in skin at the cellular level. Additionally, subsurface imaging through spatial frequency domain imaging can predict foot ulcers in diabetic patients, starting therapy earlier and reducing amputations. Coherent-spatial frequency domain imaging (c-SFDI) can be used to detect microvascular perfusion and cardiovascular disease through a low-cost, wearable device. Quantitative diffuse optical spectroscopic imaging (DOSI) can be used to gauge the effectiveness of tamoxifen in breast cancer screenings, to initially identify breast cancer, and to interrogate the effects of diet on tissue of someone who is obese. Dr. Tromberg used this final example, DOSI, to demonstrate how the computing power required for the technology can be fit onto a chip suitable for wearable technology.
Dr. Tromberg then showcased some of the work he’s done with the African Spectral Imaging Network (AFSIN), where he utilized spectroscopic biophotonic technologies to work with patient populations and physicians in Africa. Moreover, biophotonic technologies are already being developed in Africa. For example, multimodal, multi-spectral microscopes are being used for malaria detection while light detection and ranging (LiDAR) technologies for remote sensing malarial mosquitos. AFSIN introduced a doctoral program in photonics and spectroscopy in 2018, which currently has 16 students.
In short, because biological processes are dynamic and continuous, technologies that can provide dynamic and continuous feedback are required to adequately measure them. As these technologies become cheaper, they democratize human health. The goals of these technologies at large, to prevent disease, to reduce costs, and to drive economic growth, are convergent with global health goals in general.
Joint Question and Answer Period
Dr. Cohen asked Dr. Tromberg about handheld ultrasounds for measuring preterm births and whether anyone was looking at measuring bloodflow in these circumstances. Dr. Tromberg replied that Amir Gandjbakhche with NICHD and Arjun Yodh at University of Pennsylvania are each investigating this issue.
Dr. Bollinger asked about the intellectual property issues that may arise from leveraging emerging technologies internationally. Dr. Tromberg replied that the issue was very difficult, but one solution might be steering local researchers to work on local problems. Dr. Bollinger added that one of the issues he’s faced in his experience with this subject is the need to bring in commercial partners in order to scale and fund these innovations. Dr. Tromberg answered that creating local enterprise zones has proven to be a viable model both in well-known regions in the U.S. as well as worldwide.
Stating that the two biggest challenges that face primary care physicians are the diagnosis of skin and mental health disorders, Dr. Robert Einterz asked each presenter about innovations on the horizon for diagnosing these disorders more accurately. Dr. Gordon replied that behavioral testing and point of care offer hope for mental health diagnoses, especially in lower resource settings. Though it’s very much in development still, this testing involves using data collected from common wearable technologies to interrogate subdomains of behavior to identify underlying mental health tendencies. Dr. Gordon pointed to autism screening questionnaires and monitoring eye gaze through iPads for autism diagnoses as an area where the technology and understanding is more advanced.
Dr. Glass proposed to Dr. Tromberg a challenge award for someone that could come up with a cheap med cap that could be used to improve tuberculosis, HIV, and hypertension monitoring and treatment adherence. Dr. Tromberg replied that the technology for continuously monitoring hypertension through a cuff has been a longtime NIBIB project with researchers in India. In response to Dr. Gordon’s comments, Dr. Tromberg shared that there’s an opportunity for greater communication between disciplines as very few people in imaging and biophotonics are thinking about measuring mental health through surrogate markers such as eye movement and blood pressure changes.
Dr. Stangl asked for the presenters’ opinions about the best way to translate technologies from universities to affordable, low-cost options that actually deliver on their promise. Dr. Tromberg replied that much can be accomplished through knowledge transfer, as he demonstrated in his discussion of working in Yamoussoukro, Ivory Coast, but that many of these technologies are already low cost as well. Moreover, partnerships between U.S. and African institutions offer another alternative for reducing costs. Dr. Gordon echoed Dr. Tromberg’s comments about the benefits utilizing low-cost options that are already available. He used the example of open source software in the clinic in Eldoret, Kenya, that uses open source electronic medical records. He added another example where researchers created open source mental health questionnaires to replace proprietary ones for the Nepalese government to measure maternal depression. Additionally, some of these biophotonic tools such as pulse oximeters can be built by students relatively cheaply from parts available around the world.
Dr. Glass asked about the current state of point of care diagnostic technology. NIBIB hosts the Point of Care Technology Research Networks (POCTRNs), which is sponsored in part by FIC, in addition to around seven other ICs. Many of the advances in spectroscopy and therapeutics demonstrated in Dr. Tromberg’s presentation are showing up in bedside and point of care technologies as well. Dr. Ogdegbe asked how many of the POCTRNs were located in low-income countries. Dr. Tromberg replied that all of the POCTRNs are located in the U.S., but at least one of them has strong connections to global health. Dr. Povlich clarified that the POCTRN associated with FIC is allied with Northwestern University but also works with eight other universities in Africa to develop technologies to treat HIV-related infections and comorbidities.
Dr. Glass asked Dr. Gordon about the main takeaways for applying cutting edge mental health diagnostic techniques in lower resource settings. Dr. Gordon said that task-sharing efforts represent a promising opportunity for this. Health care practitioners who do not specialize in mental health can incorporate a mental health approach into their practice. Moreover, NIMH also conducts a significant amount of research in lower resource settings where much of what it learns abroad can be applied domestically in the U.S. Dr. Wasserheit asked how FIC could be more helpful to Dr. Gordon and to NIMH’s agenda. Dr. Gordon said it’s hard to say because NIMH already looks to FIC for guidance on how to maximize international investments. NIMH’s Global Mental Health Program has been developed in tandem with FIC throughout its lifetime.
Dr. Glass asked Dr. Tromberg about the ways in which FIC can better engage with NIBIB, specifically how can FIC replicate Dr. Rebecca Richards-Kortum’s success developing a relationship with researchers in Malawi with Dr. Tromberg’s contacts in Cote d’Ivoire. Dr. Tromberg praised his partners in Yamoussoukro and commented that better English among some of the students would have improved teaching and communication. The students’ enthusiasm and inquisitive nature inspired Dr. Tromberg, and he reiterated his belief that local entrepreneurial centers should be set up around the world. He also commented that, whereas biophotonic technology used to be exorbitantly expensive, it’s now cheap and available enough that it can be disseminated widely. Dr. Bollinger suggested that FIC consider directly working with bioengineering students internationally. Dr. Wasserheit echoed this, arguing for an approach where the ultimate implementation is considered from the initiation of a technological development project. Dr. Tromberg agreed, saying that there are opportunities for shared investment and risk at every level of research.
Dr. Amit Mistry introduced his work building partnerships with elite research institutions in the U.S. with global partners. Dr. Tromberg reiterated his point about the educational opportunities for domain experts to guide research internationally, as enabled by cheap and available technology. In response, Dr. Glass proposed working with NIBIB to sponsor more bioengineering fellows. He also proposed that Dr. Tromberg’s Cote d’Ivoire partners take advantage of the APTI program.
Karen Goraleski asked Dr. Tromberg about engaging the public and policymakers on innovations in biophotonics. Dr. Tromberg responded that many people understand that technology drives the economy in the U.S., though he noted that the issue of influencing policy is very domain-specific. NIBIB is actively engaged in building a portfolio of narratives around the positive impacts of its technologies in the U.S. The process was much different in Yamoussoukro, for example, where local leaders were more resistant to new technologies for social and cultural reasons.
Dr. Glass commented on the importance of technological developments in advancing global health goals. He shared an example from Rwanda where health care workers are delivering blood by drones to help women hemorrhaging during childbirth. Dr. Glass thanked everyone for their participation and closed the meeting at 2:54 p.m.