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September 14-15, 2015 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-third Meeting of the Advisory Board
Minutes of Meeting
September 14-15, 2015
Lawton Chiles International House, Building 16, Conference Room
National Institute of Health, Bethesda, MD

The John E. Fogarty International Center for Advanced Study in the Health Sciences (FIC) convened the eighty-third meeting of its Advisory Board on Monday, September 14, 2015 at 1:00 p.m., in the Stone House Conference Room, Building 16, National Institutes of Health (NIH), Bethesda, Maryland. A closed session was held prior to the open session, as provided in Sections 552(b)(4) and 552(b)(6), Title 5, U.S. Code, and Section 10(d) of Public Law 92-463, for the review, discussion and evaluation of grant applications and related information. Dr. Roger I. Glass, Director, FIC, presided.

Attendee Information

Board Members Present

Roger I. Glass, M.D., Ph.D. (Chair)
Wafaa El-Sadr, M.D., M.P.H.
Haile T. Debas, M.D.
George C. Hill, Ph.D.
Joseph Kolars, M.D.
Michael Merson, M.D.
J. Stephen Morrison, Ph.D.
Rebecca Richards-Kortum, Ph.D.
Janine Austin Clayton, M.D., ORWH (ex officio)
Gregory Germino, M.D., NIDDK (ex officio)
Walter Koroshetz, M.D., NINDS (ex officio)

Board Members Absent

Michele Barry, M.D.
King Holmes, M.D.
Bill Tierney, M.D.

Members of the Public Present

Julie Makani, Nuffield Department of Medicine, University of Oxford
John Monahan, O’Neill Institute for National and Global Health Law, Georgetown University
Shahid Jameel, Wellcome Trust-DBT India Alliance

Federal Agency Representatives Present

Duane Alexander, FIC
Wladimir Alonso, FIC
Nalini Anand, FIC
Belinda Ancarrow, FIC
Farah Bader, FIC
Kevin Bialy, FIC
Rick Berzon, NIMHD
Katrina Blair, FIC
Joel Breman, FIC
Maggie Brewinski Isaacs, NICHD
Kenneth Bridbord, FIC
Bruce Butrum, FIC
Athalia Christie, CDC
Dexter Collins, FIC
Robert Eiss, FIC
Ella Ewart-Pierce, FIC
Robert Ferris, USAID
John Flanigan, NCI
Eric Green, NHGRI
Thomas Gross, NCI
Mark Guyer, NHGRI
Gray Handley, NIAID
George Herrfurth, FIC
Flora Katz, FIC
Peter Kilmarx, FIC
Cathy Kristiansen, FIC
Linda Kupfer, FIC
Vesna Kutlesic, NICHD
Patricia Lee Callahan, FIC
Ellis McKenzie, FIC
George Mensah, NHLBI
Hedieh Mehrtash, NCI
Kathy Michels, FIC
Joseph Millum, CC/FIC
Mahendra Naidoo, NCI
Pragna Patel, CDC
Shannon Pearce, FIC
Vivian Pinn, FIC
Shana Potash, FIC
Laura Povlich, FIC
Ann Puderbaugh, FIC
Callie Raulfs-Wang, USAID
Satabdi Raychowdhury, FIC
Myat Htoo Razak, FIC
Josh Rosenthal, FIC
Hilary Sigmon, CSR
Barbara Sina, FIC
Marcia Smith, FIC
Rachel Sturke, FIC
Karyl Swartz, CSR
Kate Tapley, HHS
Myra Thomas, NIAID/FIC
Jennifer Troyer, NHGRI
Nancy Touchette, NIAID
Cecile Viboud, FIC
Susan Vorkoper, FIC
Kristen Weymouth, FIC
Mitchell Wolfe, HHS
Celia Wolfman, FIC

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Closed Session

Open Session

Director's Welcoming Remarks

Dr. Roger Glass

Dr. Glass welcomed the Advisory Board back to the renovated Stone House. The Board included three new members: Dr. Waldemara Carlo, Dr. Haile Debas, and Dr. Vanessa Bradford Kerry. Dr. Carlo is Professor of Pediatrics at the University of Alabama Medical Center and The Children’s Hospital of Alabama. Dr. Debas is Professor Emeritus at the University of California-San Francisco. Dr. Kerry is the co-founder and CEO of Seed Global Health.

Dr. Bill Tierney will be leaving the Board to take a job as the Inaugural Chair of Population Health at the University of Texas at Austin.

Dr. Peter Kilmarx is the new Deputy Director of the Fogarty International Center. He is a Captain in the US Public Health Service, and has spent 21 years with CDC.

The Board congratulated Dr. Richards-Kortum for being named to the National Medal of Science Committee, and Dr. Merson for receiving a substantial grant from the Bill & Melinda Gates Foundation.

Dr. Soumya Swaminathan has been named Director General of the Indian Council of Medical Research. Fogarty’s activities in India have been at a standstill for the past several years due to new clinical trial regulations. Dr. Glass expressed the hope that under Dr. Swaminathan will help Fogarty’s and other ICs’ efforts in India move forward.

Dr. Glass introduced Dr. Shahid Jameel, the CEO of the Wellcome Trust-DBT Alliance, a partnership between the Wellcome Trust and the government of India.

Dr. Glass participated in the World Health Assembly, held May 18-22. The Fogarty Center for Global Health Studies held its fourth and final meeting of the PEPFAR Consultation on Prevention of Mother-to-Child Transmission (PMTCT). The results will be published in the June, 2016 JAIDS Supplement. The consultation led to the launch of the Nigerian Implementation Science Alliance and catalyzed joint grant applications among Alliance members. It also led to a funding request for an extension to prevention and treatment of HIV in adolescents in PEPFAR countries. The 64th Annual American Society of Tropical Medicine & Hygiene conference will take place in Philadelphia from October 25-29. A special symposium is being held on the 27th on the opening of research with Cuba. Topics will include vaccines, tropical diseases, biotechnologies, and the Ebola outbreak response.

Update on the Common Rule

Dr. Joseph Millum, Division of International Science Policy, Planning and Evaluation, FIC

Dr. Millum briefed the Board on potential changes related to the Federal Policy for the Protection of Human Subjects, also known as the Common Rule. The issue was discussed at a recent meeting of the NIH Institute Directors and is of critical importance to Fogarty’s biomedical research programs.

The Common Rule is the set of regulations that requires ethics review of all federally-funded research involving human subjects. These reviews are conducted by Institutional Review Boards (IRBs). The Rule is also followed optionally by institutions that do not receive federal funding but wish to provide ethical review of their research involving human subjects. The scope of the regulations is international because any international research supported by U.S. funding must also adhere to its requirements. Similar FDA regulations apply to data acquired from human subjects’ research that are submitted for FDA marketing approval.

The Notice of Proposed Rule-making (NPRM) was recently published in the Federal Register soliciting public comment. The 90-day comment period will end on December 7, 2015. After review of the public comments, a final rule will be announced and its changes to the Common Rule will be implemented. The proposed changes contained in the NPRM seek to enhance safeguards for research participants and to improve the efficiency of the ethics review system. The current IRB system has been widely criticized as being overly bureaucratic and inefficient.

The NPRM proposes an expansion of the Common Rule’s scope to ensure that more high risk research is covered by the regulations. The new regulations will cover all clinical trials, regardless of funding source, that are conducted at a U.S. institution that receives federal funding for non-exempt human subjects research. The proposed changes are also intended to streamline the review process for lower risk studies. The proposed rules define new areas of research that are excluded from review, such as journalism, historical scholarship and quality assurance studies, as well as certain low risk research studies.

Currently, studies requesting an exemption must go through administrative or IRB review. The NPRM would allow for the exemption determination to be conducted without IRB review, either through a standardized tool or through an institutional expert. However, the NPRM does allow for institutions to require limited IRB review of consent processes and privacy safeguards. The NPRM will also eliminate the continuing review requirement for all studies that undergo expedited review and studies that have completed their study interventions. U.S. institutions engaged in multiple sites must rely on a single IRB for that portion of the study that takes place within the United States. Dr. Merson asked whether the single IRB requirement will apply to clinical research only or all research conducted at an institution. Dr. Millum said it will apply to any multisite cooperative research that takes place within the United States.

The NPRM will allow for the use of a broad consent for collection and use of biospecimens and identifiable data. It will also establish restrictions on waivers of consent for research involving biospecimens. Dr. Richards-Kortum asked how these changes will affect specimens already collected. Dr. Millum said it is his understanding that the new rules will not apply to existing banked specimens.

Another goal of the NPRM is to reduce the amount of verbiage and improve the clarity of consent documents. Under the proposed rule, the consent form may only contain consent elements required by the regulations. Any additional consent elements must be contained in a separate appendix. The NPRM requires that participants be provided with the information a reasonable person would need to make an informed decision, and the opportunity to discuss that information.

Dr. Millum encouraged the submission of public comments. Dr. Hill asked when the final rule is expected to be published. Dr. Millum said he anticipated the rule would benefit finalized sometime in the spring of 2016. Dr. Glass said he looked forward to the implementation of the final rule, which he hoped will streamline and simplify the research process and facilitate the use of precision medicine and large cohort studies.

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Fogarty’s Ebola-Related Activities and Concept Proposal

Dr. Peter Kilmarx, Deputy Director, FIC
Dr. Cecile Viboud, Staff Scientist, Division of International Epidemiology & Population Studies (DIEPS), FIC
Dr. Ellis McKenzie, Senior Scientist, RAPIDD Director, DIEPS, FIC
Dr. Flora Katz, Acting Director, Division of International Training & Research, (DITR) FIC

There have been more than 28,000 cases and over 11,000 deaths associated with the recent Ebola outbreak in West Africa. Dr. Kilmarx presented an overview of FIC’s Ebola response and its participation in a National Academy of Medicine commission. Before joining FIC, Dr. Kilmarx was the Centers for Disease Control and Prevention’s (CDC) Sierra Leone Ebola Response Team Leader (September 18-October 16, 2014) and Guinea Ebola Response Deputy Team Leader (January 6-February 4, 2015). Dr. Maria Said, former program officer in DITR, was deployed with the US Public Health Service (USPHS) for three months as a physician treating patients at USPHS’ Monrovia Medical Unit in Liberia. Kevin Bialy, program officer in FIC’s Division of International Relations (DIR), was deployed with the CDC Rapid Assessment Teams in Liberia and Sierra Leone from March 22-May 22, 2015. Dr. Mark Miller, DIEPS Director, served as the National Institute of Allergy and Infectious Diseases’ (NIAID) clinical team lead for its ZMapp trial in Sierra Leone from June 14-July 2, 2015.

NIH has joined the National Academy of Medicine’s international commission to create a global health risk framework. The commission is currently holding workshops focused on resilient health systems, research and development, financing, and global health governance. Dr. Kilmarx serves as NIH’s representative on the commission’s research and development work group. The commission’s report is due in January 2016.

Dr. Cecile Viboud

Dr. Viboud and her team began by looking at virus sequence data to try to understand the origin of the epidemic and its spatial spread. From 100 virus sequencings from a hospital in Sierra Leone, phylogenetic analysis was able to trace the origin of the virus within the last decade from a Central African genetic reservoir. The reservoir was genetically diverse and also responsible for an earlier outbreak in the Democratic Republic of the Congo. These sequencings suggested that the outbreak emerged from a single zoonotic transmission event in Guinea. The rest of the outbreak was fueled by human-to-human transmission. The analysis was able to pinpoint the spread of the virus from Guinea to Sierra Leone in May 2014, which corresponded with independent reports of a large funeral event involving cross-border movements between the two countries. Further analysis from virus sequencing showed that if not for this funeral event, the outbreak likely would have ended in May 2014, when one of the early virus lineages became extinct in Guinea.

Dr. Viboud and her collaborators looked at epidemiological data from the outbreak to attempt to infer the transmission dynamic and predict the efficacy of control interventions. Dr. Viboud presented a slide showing a transmission tree from the outbreak in Nigeria where an initial case led to twelve secondary cases but declined sharply afterwards due to strong intervention efforts. Her team attempted to create a transmission tree for the larger outbreak but the early data was highly aggregated. In order to find more detailed data, the researchers looked at news reports from the internet that described how transmissions occurred within families and hospitals. Using this data, they were able to produce some general statistics which can then be used in mathematical models to try to infer the impact of intervention strategies.

Dr. Viboud discussed an Ebola forecasting challenge being launched by Fogarty’s Research and Policy for Infectious Disease Dynamics (RAPIDD) program this fall. The goals of the initiative are to improve the utility of disease models for infectious disease crises, train modeling teams in “peace time,” and compare the prediction accuracy of mathematical models. A number of academic teams presented disease models during the recent Ebola outbreak, but these efforts were not well-organized. The forecasting challenge should help researchers develop best practices for coordination in the event of future crises. Participating research teams will be presented with several scenarios related to the West African Ebola outbreak and be asked to use the provided data to make predictions at six time points during the epidemic and then compare the different projections.

Dr. Ellis McKenzie

Dr. McKenzie, Director of the RAPIDD program, briefed the Board on additional efforts in response to the Ebola outbreak. Dr. Simon Hay is part of a team that produced a paper detailing the risk of future zoonotic transmission of Ebola. The team mapped the 23 individual outbreaks in humans that have been identified during the recent epidemic and the 51 locations where infected animals have been reported. This occurrence data was compared with environmental covariates and distribution data on suspected reservoir bat species to model a zoonotic transmission niche. This model covered 22 countries across Central and West Africa, 15 of which have not had an Ebola outbreak. It should be noted that the study presents suitability, and not prediction, models.

Another study, involving Fogarty researcher Dr. Andy Tatem, looked at creating analytic tools using call data records (CDRs), which can track the movement and location of mobile devices during epidemics. CDRs can allow researchers to infer where people are, how many people are at a given location, and where people might be headed. These tools can also track details of an epidemic in real-time, enabling response teams to effectively target interventions. Dr. Tatem has used these tools in crises in Haiti, Nepal, and elsewhere. Studies involving the use of CDRs raise serious questions about data privacy and other legal concerns.

One paper, published in June, assessed two designs for Ebola vaccine trials in Sierra Leone: a randomized control trial (RCT) and a stepped-wedge cluster trial (SWCT). The use of RCTs has raised ethical concerns because the assigning of a control group involves the risk of infection. In theory, SWCTs avoid this problem by vaccinating all participants in a random sequence of geographically distinct clusters of individuals to allow unbiased comparison between vaccinated and unvaccinated clusters. The paper concluded that the spatio-temporal variation of infection risk undermines the statistical power of SWCTs. It also undercuts the SWCT’s expected ethical advantages because an RCT (but not an SWCT) can prioritize vaccination to high-risk clusters. Given identical logistical constraints, the power of an SWCT to detect an effective vaccine is three to ten times lower than a risk-prioritized RCT in the same population.

A paper published in Science in March built on the observation that the Ebola outbreak had disrupted healthcare services and vaccinations across the affected areas, creating a secondary health crisis. The study focused on measles and other childhood infections and projected that each month of disruption would lead to an additional 20,000 unvaccinated children across Guinea, Liberia, and Sierra Leone. After 18 months, this enlarged pool of susceptible children would increase the expected size of a regional measles outbreak by 100,000 cases, resulting in an additional 5,000 deaths.

Aaron King and Pejman Rohani used a simulation study to show how some widely used modeling practices lead to potentially large errors in parameter estimates and model-based forecasts. Their paper demonstrated a straightforward, computationally inexpensive alternative based on stochastic models fit to weekly WHO Ebola case reports from Guinea, Liberia, and Sierra Leone through October 1, 2014. This approach reduces bias, better quantifies uncertainty in estimates and forecasts, and lack of model fit is more readily diagnosed.

An October 2014 paper published in The Lancet built on observations that serosurveys after outbreaks in Gabon in 1996 found that 71% of seropositive individuals did not have Ebola. In addition, 46% of asymptomatic close contacts of patients with Ebola were seropositive. Although asymptomatic infections are unlikely to be infections, they might confer protective immunity and thus influence projected incidence and complicate the interpretation of clinical trials. Assays that reveal asymptomatic infections and/or antibody titers do not necessarily imply asymptomatically acquired protective immunity.

Dr. Flora Katz

Dr. Flora Katz, Acting Director, Division of International Training & Research, presented to the Board a concept proposal to increase research capacity in Liberia, Guinea, and Sierra Leone, the three most affected countries in the recent Ebola outbreak. This outbreak has highlighted the fragility of the healthcare infrastructure, weakness of the existing research capacity and raised many important research questions in these countries. Dr. Katz and her team have developed a concept proposal in order to see what role Fogarty has in helping address these issues.

The team decided to work from Fogarty’s strengths in capacity building. The concept proposal seeks to focus on viral emerging infectious diseases with the potential to become regional or global epidemics. Potential areas of focus for research and training include early identification, transmission prediction, and research to improve the public health response. Other focus areas include mental health and stigma-related issues, recruitment and conducting of clinical trials during outbreaks, and the nature of and response to chronic health sequelae in survivors.

Fogarty would work with institutions in other African countries that have relevant expertise and existing partnerships; encourage linkages between these institutions and international partners with the goal of creating networks among African institutions and investigators capable of collaborating around these issues; and help these institutions develop appropriate research agendas and interventions and leverage international initiatives in the three affected countries.

The proposal calls for two-year planning grants for US or African research institutions to plan research, training, and capacity building programs in Liberia, Sierra Leone, or Guinea focused on emerging viral epidemics. US applicants will be encouraged to include other African institutions as collaborators in order to develop South-South training and foster research networks. Planning should be directed towards developing partnerships and opportunities for FIC research or research training programs. Fogarty already has a number of existing programs relevant to this proposal.

Discussion

Dr. El-Sadr said the focus on planning grants in the concept proposal is a smart idea. There are very few institutions on the ground in the countries in question and it will take time to identify and build capacity in the institutions that do exist. Dr. El-Sadr also felt the plan to triangulate with other African institutions was a good way to foster the ideal partnerships. One recommendation would be to look into implementation science research as a focus area, because programmatic inquiries are another important subject that is lacking in the three countries. Dr. Morrison said the proposal is very timely with a number of international Ebola-related panels about to release their reports in the coming months. While academic infrastructure in the affected countries may be lacking, looking towards existing NGOs on the ground may prove fruitful.

Dr. Kenneth Bridbord asked whether the grant proposal would exist as a one-year or two-year RFA. In light of the ongoing release of new reports from international panels, the logistical difficulties related to receiving electronic submissions from low and middle income countries, and the benefits in allowing time for amended applications, a two-year RFA period might be advisable. Dr. Katz said that decision has not been made yet, but any input will be taken into consideration. Dr. Merson asked if the two-year grants will be followed up with stand-alone training grants, or if they are expected to feed into other existing, relevant funding opportunities. Dr. Katz said that Fogarty is not planning on developing a stand-alone initiative because her team felt that FIC’s existing programs are sufficient to accommodate the required technical capacity. Dr. Hill asked what types or organizations and institutions in the three countries Dr. Katz sees as potential candidates for the planning grants. Dr. Katz said she did not know; one of the purposes of the planning grants is to identify which institutions and entities exist in the country to build around. Mr. Monahan said it was wise to build in as much flexibility as possible for the RFA process, and important to communicate with the local ministries and stakeholders.

Dr. Glass asked Mitch Wolfe from HHS and Athalia Christie from CDC how the concept proposal would interact with existing federal programs. Dr. Wolfe said he had heard from one Ministry of Health that the academic institutions in its country were in good condition, but it was the Ministry of Health that needed help building capacity. Ms. Christie spent eight months in Liberia working for CDC’s Ebola response and heard repeated concerns that the Ministry of Health was completely overwhelmed with external partners coming in to build capacity. The result has been lack of communication between funding agents, which has led to parallel funding and programs. Ms. Christie said the proposal targets crucial areas of need, but it will be very important to maintain a high level of coordination with existing programs on the ground. Rick Berzon, from National Institute on Minority Health and Health Disparities (NIMHD), asked to what extent FIC reviewed models and lessons learned from the Medical Education Partnership Initiative (MEPI) program in other African countries. He has heard from a number of people that African institutions often feel unqualified to apply for NIH grants. Dr. Katz said she sees this proposal as having a different focus than MEPI, which was geared toward medical schools, whereas this proposal is aimed at building capacity and expertise through the work of individual researchers.

Dr. Debas asked whether partnering with Ministries of Health can be made a condition of application for the grants. Dr. Katz said NIH has limiting conditions on its grant proposals, and this proposal would be limited to Africa and the three affected countries, but she felt it would be difficult for NIH to allow Fogarty to put such constraints on the applicants. That said, Fogarty can encourage certain things, and applicants would be expected to listen. Dr. Julie Makani said she was skeptical that putting emphasis on partnerships with ministries would be as effective as working with institutions at the forefront of the response. She recommended looking at NHGRI’s H3Africa initiative as a model of a successful pan-African program.

Dr. Morrison advised FIC staff to consult the Global Health Security Agenda country plans for the three countries. With the flood of funding and programs going to these nations, it will be crucial to stay abreast of existing international initiatives. The World Bank Ministry of Health recovery plans are another source for potentially helpful information. Dr. Glass noted that Fogarty fills a particular niche, capacity building, which is important to remember in such a complicated landscape. For potential organizations to consult for advice, particularly in Liberia, Dr. Morrison mentioned the Clinton Health Access Initiative (CHAI), Last Mile Health, Partners in Health. Dr. El-Sadr said that one way to make sure the research is responsive to needs is to encourage a process that includes consultation with ministries, academics, and key stakeholders in-country. Mr. Monahan recommended consulting early on with relevant US government agencies because they will be able to provide an accurate picture of where US funding is being targeted. He echoed the call to give grant applicants as much flexibility as possible to make adjustments with such a fluid scenario on the ground.

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PEPFAR-NCD Project: Enhancing HIV/AIDS Platforms to Address NCDs in Low Resource Settings

Ms. Nalini Anand, Director, Division of International Science Policy, Planning and Evaluation; Director, Center for Global Health Studies, FIC
Dr. Wafaa El-Sadr, Director, ICAP; Director, Global Health Initiative, Columbia Mailman School of Public Health; Board Member

Ms. Anand presented an overview of Fogarty’s Center for Global Health Studies’ strategic plan addressing non-communicable diseases (NCDs) in the HIV/AIDS community. The strategic plan is the result of collaboration between FIC, multiple NIH Institutes, and the Federal PEPFAR program. The strategic plan places an emphasis on implementation science, models of knowledge translation, and how to best engage policy makers and program implementers in achieving the goal of addressing NCDs. The plan brings different disciplines together to look at existing research and care infrastructure, and how to best leverage that infrastructure to work on the broader NCD agenda in the HIV-infected population. Other areas of focus are looking at the uptake of evidence into policy and practice, the dual burden of communicable and non-communicable diseases, and building partnerships to advance the global health research agenda.

The goal and the purpose of the project is to bring together a diverse group of individuals - researchers, implementers, and government agencies – to develop a research agenda related to prevent and manage NCDs. The project aims to incorporate NCD prevention and management interventions into the HIV platform in the low and middle income countries supported by PEPFAR. Fogarty’s efforts have been supported by a $1.5 million grant from PEPFAR.

Fogarty has established a secretariat for the project, based in the Center for Global Health Studies, that includes representation from agencies such as the CDC and USAID. A steering committee was established, co-chaired by Dr. El-Sadr and Dr. Bill Tierney. A technical working group was also created, which includes representatives from numerous government agencies and many NIH Institutes. It met at the FIC in September of 2014 and decided to focus the project on four primary NCDs: cervical cancer, cardiovascular disease and stroke, depression, and diabetes. Three technical operating groups (TOGs) were created to help focus the committee’s work. One was tasked with disease and condition, the second focused on health system integration, and the third covered awareness, education, and dissemination.

Since the meeting last September, each of the TOGs has worked to identify priority research questions and produce a paper on their respective topic areas. Meanwhile, Fogarty staff has been conducting key informant interviews with Ministries of Health and academics in the four countries the technical working group chose to focus on. In addition, staff reviewed each country’s existing HIV policies, infrastructure, and NCD-related health facility capacity surveys. The technical working group subsequently held its second meeting this past July. The goal of the meeting was to bring together a diverse group of researchers, implementers, and policy makers to dig deeper and come up with a research agenda and strategy going forward. The meeting resulted in several next steps:

  • Incorporate NCD-HIV questions into existing surveys, such as the IeDEA survey and WHO STEPS survey;
  • Model NCD prevalence in project focus countries in collaboration with DCP3; develop a country-level compendium of existing NCD protocols, policies and guidelines;
  • Refine and prioritize NCD-HIV integration implementation science research; compare the current integration models;
  • Prioritize and develop NCD awareness, education, and dissemination resources for persons living with HIV; and
  • Edit and publish the landscape analyses developed by the TOGs over the past year.

Dr. Glass noted that the activities of this program fall outside of what might be traditionally seen as core PEPFAR activities. He asked how Dr. El-Sadr saw that playing out as the project moves forward. Dr. El-Sadr agreed that the activities are non-core, but there is a growing consensus that as people living with HIV live longer, they will begin to develop more NCDs. In that sense, the project fits well with the goal of preventing morbidity and keeping people healthy. Dr. Glass asked Dr. El-Sadr how she might use the outcomes of this project to influence her work with NCDs at ICAP. Dr. El-Sadr said ICAP helps support Ministries of Health to do their work, and the ministries have shown interest and receptivity in preliminary projects focused on integration of NCD screening in HIV programs. Dr. Debas said focusing on NCD prevention would be highly valuable in many of these countries. Dr. El-Sadr agreed and said there are many opportunities for NIH Institutes to develop programs around their areas of expertise. Dr. John Flanigan said the National Cancer Institute (NCI) just published a P20 funding announcement for the combined centers of excellence to study NCDs. Dr. Kilmarx said it will be important to have a pathway to implementation, with clear models, so there is an audience for the research. It will be crucial to have someone in-country tasked with implementation. Ms. Anand said staff is looking at one or two regional meetings in Africa, and has been working hard to ensure Sub-Saharan Africa’s representation on the steering committee.

Dr. Glass thanked everyone for their great presentations and active participation and adjourned the meeting for the day at 4:49 p.m.

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Day Two - Director’s Update and Discussion of Current and Planned FIC Activities

Dr. Roger Glass

The Heads of International Research Organizations (HIRO) met contemporaneously with the Global Alliance for Chronic Diseases (GACD) Board meeting in Ottawa, in June. NIH was represented by its Director, Francis Collins. The GACD has served as a good meeting place for global funders to work on synergizing their efforts. This year a focus was placed on expanding hypertension programs, diabetes research, and scoping global mental health.

Fogarty received a number of international visitors this summer, including Liu Yandong, the Vice Premier of China, and Khalid Al-Falih, the Saudi Minister of Health. Minister Al-Falih has been active in funding research at NIAID related to the MERS virus. Queen Letizia of Spain will visit the NIH on September 16.

The Fogarty Fellows and Scholars and Fulbright-Fogarty Fellows orientation was held in July. The programs currently support 85 post-doctoral fellows and graduate scholars at over 20 sites in low and middle income countries.

The Medical Education Partnership Initiative (MEPI) 5th Annual Symposium was held July 14-16 in Zimbabwe. Fogarty has been working for some time to renew the MEPI grant. Dr. Glass and FIC representatives will be meeting this week with the Office of the US Global AIDS Coordinator to try to finalize the grant renewal. Ten NIH Institutes have contributed approximately $36 million to continue MEPI research in the form of developing junior faculty of MEPI institutions. This funding will enable the program to support eleven grantees for research in eight countries.

Fogarty’s Center for Global Health Studies hosted the second PEPFAR-NCD steering committee meeting in late July. The committee is co-chaired by Drs. El-Sadr and Tierney. Dr. Agnes Binagwaho, Rwandan Minister of Health, delivered the David E. Barmes Global Health Lecture on July 28th. The lecture was attended by NIH Director Francis Collins, NIDCR Director Martha Somerman, and the Rwandan Ambassador to the US.

NIH Director Dr. Collins and Sylvia Burwell, Secretary of Health and Human Services, visited South Korea in early September of this year. Dr. Collins toured the Seoul National University Hospital Biomedical Research Institute and met with NIH grantees and alumni. He visited the International Vaccine Institute and the Korea National Institute of Health-Osong Campus Biobank.

Rob Eiss will be speaking at the 3rd United Nations General Assembly Side Meeting on September 27. Professor Steve Tollman, from the University of Witwatersrand in South Africa, will be visiting September 28-29. Dr. Tollman has four active NIH grants studying rural populations in South Africa. Elsewhere, Drs. Barbara Sina and Joe Millum will be leading a Bioethics Training Program network meeting October 5-6. In November, they will travel to France for the Global Forum on Bioethics in Research. The mHealth Program has a network meeting scheduled for October 14, and the NIH will host the 5th Annual Wireless Health Conference on October 15-16. On November 18, Dr. Chris Murray will be delivering a lecture at NIH and will hold three side sessions on high resolution spatial mapping, new insights on NCD risk factors, and surprises from the global disease burden study in the US.

The 64th Annual American Society of Tropical Medicine & Hygiene conference will take place in Philadelphia from October 25-29. A special symposium is being held on the 27th on the opening session on research with Cuba. Topics will include vaccines, tropical diseases, biotechnologies, and the Ebola outbreak response.

Dr. Glass asked Ms. Anand to give a brief update on the activities of the Center for Global Health Studies (CGHS). CGHS held its final PMTCT Alliance meeting in May. The PEPFAR-NCD project held its second meeting this past July. The Clean Cooking Implementation Science Network will meet in October. In November, a CGHS-led paper on brain disorders in low and middle income countries will be published in Nature. The Center is working on a study on childhood obesity in Latin America that has an estimated publish date of March 2016.

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Human Heredity and Health in Africa (H3Africa) Update

Dr. Eric Green, Director, National Human Genome Research Institute (NHGRI)
Dr. Jennifer Troyer, Program Director, H3Africa, NHGRI

Dr. Green gave the Board a brief overview of the program’s history, which traces its origins to seven years ago when NIH Director Dr. Collins was the Director of NHGRI. Once Dr. Collins became Director of NIH, he was able to establish H3Africa as a partnership between the Common Fund and Wellcome Trust.

The overall vision of H3Africa is to enhance capacity for using contemporary research approaches in Africa by African scientists, to understand the genetic and environmental factors that determine disease susceptibility and drug responses in African populations. As part of this vision, H3Africa aims to increase the number of internationally competitive African scientists in genomics and population-based research, establish collaborative networks of African investigators, create and expand infrastructure for genomics research, and support the ongoing policy development for ethical issues in genomics research in an African context.

H3Africa awards cover topics in bioethics, infrastructure, and biomedical research. Twenty-five of the studies are NIH-driven, and three are led by the Wellcome Trust. The studies are researching a wide array of diseases and disorders. The infrastructure programs are working on developing biorepositories and expanding their capacity. H3Africa holds a biannual consortium on the African continent to meet with stakeholders and gather researchers to discuss common problems and initiatives. The next consortium will take place in DC, and will include a visit of the NIH campus.

Dr. Troyer was particularly proud of the program’s strides in fostering collaboration. The program consortium is highly active working on areas of common interest. The program has over 250 trainees supported through H3Africa projects.

One of the main areas where the program hopes to create sustainability is by leveraging resources to improve infrastructure. Dr. Troyer discussed H3ABioNet, a pan-African bioinformatics network for the H3Africa program. The program is based at the University of Cape Town in South Africa, and the Principal Investigator is Dr. Nicola Mulder. The BioNet is the largest single H3Africa investment and has 32 affiliated research groups in 15 countries across the continent. The program has developed policies and procedures for data deposition, quality control, data transfer, and data sharing and access.

At the end of the program, H3Africa hopes to have established infrastructure for a pan-African bioinformatics capacity, three DNA biorepositories, ethical guidelines and best practices, and a flourishing collaborative community with a culture of data and sample sharing. The goal is to collect 70,000 DNA samples with a subset of harmonized phenotypes and a broad representation of different ethnolinguistic and environmental backgrounds and disease states.

Discussion

Dr. Hill asked how H3Africa ensures that study participants are fully informed prior to participation. Dr. Troyer said the groups are all highly aware of the issues related to informed consent and continually assessing the consent process. Community engagement committees, data and biospecimen access committees, and ethics review committees have been created to help the program maintain a high level of ethical responsibility. The second stage will require a certain amount of spending on community engagement and evaluation. Dr. El-Sadr brought up the President’s Precision Medicine Initiative and how the findings from H3Africa relate back to precision medicine here in the United States. Dr. Green said that the goal of the US initiative is to create a national cohort that can be compared with other cohorts around the world. Much of the study will be longitudinal and focus on quality of care in what is a relatively infrastructure-rich nation. H3Africa is more focused on discovering the genomic basis of disease and is not following people longitudinally like the Precision Medicine Initiative will be. Mr. Monahan suggested looking at the various research hubs as an asset that gives remarkable community access that could potentially be leveraged in creative ways. Dr. Glass suggested one possible use of the H3Africa network is for studies on Ebola survivors, of which there are many thousands, and who US researchers have very little access to. Dr. Makani said H3Africa has done a lot already to change the dynamics of collaboration and funding in Africa.

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Indoor Air Pollution/Cookstoves

Dr. Josh Rosenthal, Senior Scientist, DIEPS, FIC

Recent years have seen a growth of interest in household air pollution in the global health community, in part due to the most recent revision to the Global Burden of Disease study. The World Health Organization estimates 4.3 million early deaths per year associated with household air pollution. There are an estimated 3 billion people without access to clean cooking safeguards. Cross-sectional studies indicate that clean cooking can yield potentially huge benefits for acute respiratory infections, stillbirths, low birth weight, cardiovascular disorders, and cancer. Investments in improved cooking technology and access to cleaner fuel sources are underway, but currently the studies lack proof of principle that a population scale intervention can make significant difference in health status.

The Global Alliance for Clean Cookstoves (GACC) was established in 2010 to lead the global effort towards lowering household air pollution due to cooking. The GACC attempts to build cookstove programs around the world to replace polluting fires with cleaner cooking technologies. The NIH is concerned that so far there is a lack of evidence that proposed replacement technologies have anything more than a modest impact on health. Most replacements have been biomass-oriented; while biomass is more efficient than traditional fuel sources, the health benefits have so far proven negligible. If other organizations were going to focus on stove and fuel development and distribution, the NIH would work on field evaluation of stove distribution, exposure and toxicity evaluation, research capacity building, proof of principle studies, among other areas.

Dr. Rosenthal presented three initiatives that NIH has established in support of these efforts: a Health Outcomes Interventional Trial, the Clean Cooking Implementation Science Network, and GEOHealth Hubs. The goal of the Health Outcomes Trial is to attempt to establish proof of principle that a clean cooking intervention can be developed that will yield significant benefits to health. The Implementation Science Network is tasked with developing a consensus on best practices for adoption and use of clean cooking technology, and to facilitate and support experimentation in fuel and stove distribution program efforts. The GEOHealth Hubs will form the GEOHealth Network, which will serve as a platform for coordinated environmental and occupational health research and research training activities.

Dr. Glass noted that the global burden of health related to household air pollution was doubled in the recent revision due to its effect on risk factors for stroke. He asked Dr. Koroshetz, Director of the National Institute on Neurological Disorders and Stroke (NINDS) to give the Board some background on this decision. Dr. Koroshetz said there have been studies showing the association between air pollution and stroke. The difficulty is dissociating the effect of pre-existing conditions in individuals from the effects of the air pollution. Dr. Hill asked if there is a gender bias associated with who is most affected by household air pollution. Dr. Rosenthal said the early assumption was that women and children would be most affected. This assumption is mostly true, especially in the short term, but the recent reevaluation of the burden of disease showed a higher burden in men for some of the more chronic disorders, such as cardiovascular disease. Dr. Clayton noted that sex and gender have been considered from the very beginning in the study of household pollution and the evidence is very robust.

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Falsified Drugs

Dr. Joel Breman, Senior Scientist Emeritus, FIC

Dr. Breman traced his interest on the subject to his work on tracking artemisinin resistance in the treatment of malaria. Dr. Glass chose to bring this subject to the Board’s attention, although it is not traditionally within the purview of FIC, because the loss of artemisinin as a treatment for malaria would be devastating to the global health community. He asked the Board to consider what part of the problem could NIH address and how Fogarty should get involved, if at all.

Falsified drugs can often be virtually indistinguishable from true medicines to the naked eye. Artemisinin resistance was first noticed in the mid-2000s along the Cambodian-Thai border. By 2009, a study published in the New England Journal of Medicine found that widespread marketing and use of counterfeit or falsified antimalarial drugs, often containing traces of artemisinin, not only leave cases of life-threatening malaria inadequately treated, but also exert additional selective drug pressure that could lead to resistance. A 2012 study by one of Dr. Breman’s students found that 35% of drugs sampled in Southeast Asia failed chemical analysis and 36% were classified as falsified. A similar number failed chemical analysis in Sub-Saharan Africa, with 20% classified as falsified. These findings created a storm of interest around the world, and Dr. Breman and his team were asked to speak at numerous meetings and conferences, which led to the publication of a supplement in the American Journal of Tropical Medicine.

Dr. Breman argued that the problem of falsified drugs should be classified as a pandemic. From 2013 to 2015, the WHO had 700 suspect products reported with incidents occurring in 73 countries. Pfizer Global Security reported finding falsified drugs in 107 countries in 2014 involving 69 products, and supply chain breaches in 60 countries related to 26 medicines. All of these numbers are significant increases from 2008.

There are at least 15 diagnostic systems available at various costs, seven of which are for field testing, the rest of which require a central laboratory. Epidemiological studies have suggested that up to 41% of the 16,800 medication samples studied by researchers failed to meet specifications. One study extrapolated that 15% of deaths of children under 5 due to malaria in Sub-Saharan Africa could be attributed to fake drugs, the equivalent of 122,000 children. Policy-wise, 70% of low income countries have no functioning regulatory bodies. National laws are fragmented and often weak. There is no international convention for testing.

Dr. Breman’s recommendations are to create surveillance in all countries, develop a science and technological agenda, establish an active leadership organization, and to strengthen national and international laws.

Dr. Bridbord asked Dr. El-Sadr if the issue of fake drugs has been discussed at PEPFAR. This could be a major issue for the HIV community since they are in many cases taking their medications for life. Dr. El-Sadr said the topic has been discussed and there are some safeguards in place determining which drugs can be purchased using federal funding. Many countries require that any drugs imported must be on the WHO’s prequalified list. Dr. Glass said the World Bank is considering a program to purchase mass supplies of artemisinin, which they will then distribute for close to nothing in order to try to remove the economic incentive for falsification. Dr. Breman said there have been several initiatives along that line in the recent past, though implementation has been erratic. Dr. Debas said the problem of fake drugs is a huge issue, both in health terms and for economic reasons. Dr. Glass said if the issue could get on the agenda of the UN General Assembly there could perhaps be a trickle-down effect from government leadership. Dr. El-Sadr suggested there might be linkages with existing Fogarty programs, such as mHealth. The Board agreed that Fogarty should focus its efforts on innovation.

Adjournment

Closing Comments, Dr. Glass

Dr. Glass thanked everyone for their attendance and contributions, and adjourned the meeting at 12:10 p.m.

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