Monday, April 14, 2014

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Network of Minority Health Research Investigators (NMRI) 12th Annual Workshop

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institutes of Health (NIH)
Natcher Conference Center, NIH

Bethesda, MD

April 14–15, 2014
Draft Summary Report
Monday, April 14, 2014

Trudy Gaillard, Ph.D., R.D., C.D.E., Assistant Professor, The Ohio State University

Lawrence Agodoa, M.D., Director, Office of Minority Health Research Coordination (OMHRC), NIDDK, NIH

Dr. Gaillard, Planning Committee Chair, welcomed the meeting attendees. Dr. Agodoa, OMHRC Director, also welcomed participants and noted that many were attending the NMRI workshop for the first time. He expressed gratitude to the Planning Committee for organizing the workshop and then asked participants to introduce themselves with their name, institution, and area of research. Participants ranged from the postdoctoral to the professor level, and research areas included diabetes, obesity, inflammation, health disparities, epidemiology, endocrinology, nephrology, nutrition, and cancer metabolomics.


Griffin Rodgers, M.D., M.A.C.P., Director, NIDDK, NIH
Dr. Rodgers, NIDDK Director, asserted that the NIH is very interested in programs like the NMRI and has recently named Dr. Hannah Valentine as the new Chief Officer for Scientific Workforce Diversity. Dr. Rodgers welcomed newcomers to the NIDDK “family” and emphasized that the interactions with colleagues at these NMRI Workshops are nothing less than life-changing. He thanked the members of the NMRI Organizing Committee for their work.
The NIDDK is the fifth-largest institute at the NIH. Its mission is to support and conduct research to combat diabetes and other endocrine and metabolic diseases; liver and other digestive diseases; nutritional disorders; obesity; and kidney, urologic, and hematologic diseases. The diseases under NIDDK’s purview are largely chronic, common, and consequential. Within NIDDK, there are three divisions: (1) Diabetes, Endocrinology, and Metabolism (DEM); (2) Digestive Diseases and Nutrition (DDN); and (3) Kidney, Urologic, and Hematologic Diseases (KUH). The NIDDK also supports a Division of Intramural Research, as well as extramural activities. Its core principles are to:
1) Maintain a vigorous investigator-initiated research portfolio.

2) Support pivotal clinical studies and trials.

3) Preserve a stable pool of talented new investigators (one of the missions of the NMRI).

4) Foster exceptional research training and mentoring opportunities.

5) Ensure knowledge dissemination through outreach and communications.
Dr. Rodgers provided an update on NIDDK activities. The NIDDK has engaged in numerous outreach and communications efforts, including the launch of a new website in December 2013. Although the feedback that NIDDK received from the general public and patients was generally positive, investigators did not find the old website satisfactory. Researchers sought to learn about NIDDK activities—specifically, the areas of research that would be funded by the Institute. The new website provides a direct link to research and funding opportunities for investigators to identify funding opportunities and filter them according to various criteria (e.g., career stage, funding mechanism). It is possible to subscribe to this list by RSS feed or email to receive the announcements as soon as they are released.
The NIDDK website also was reorganized to provide a list of upcoming meetings and events of interest to NIDDK-supported investigators, in part to help the research community feel connected. Dr. Rodgers drew attention to a meeting scheduled for the following year targeting principal investigators (PIs) within the first 2–3 years of their first R01 grant. The renewal of the initial R01 grant is a stage at which many investigators are lost from the research community, and the workshop is intended to remedy this. There also will be a workshop tailored to investigators supported by a K award who will be applying for their first R01 grant.
The NIDDK supports several different efforts to promote diversity and increase the numbers of underrepresented ethnic groups, as well as individuals with disabilities. Additional information for each initiative, including the point of contact, is available on the NIDDK website. The website also provides a research resources link to a central repository that supports clinical trials and clinical studies, including a database, made available by the NIDDK, with genetic information and clinical samples for investigators to share. The database contains a list of the various resources that are available and is searchable by disease. Again, an option to receive updates to the resources via email is available.
The NIDDK Central Repository now houses millions of biological samples collected from myriad studies. Investigators can apply to access various genetic samples or data sources. Samples were collected from large trials, such as the middle-school-based primary prevention trial of type 2 diabetes known as HEALTHY and the Program To Reduce Incontinence by Diet and Exercise (PRIDE).
The NIDDK supports the National Diabetes Education Program (NDEP), which disseminates knowledge and lessons learned from major clinical trials to patients and providers. Controlling diabetes can decrease the risk of developing secondary complications, and this diabetes prevention program takes small steps to reap large rewards. The campaign materials are distributed in English and Spanish, as well as several Asian and Pacific Islander languages. To amplify the impact of the program, the NIDDK partners with organizations that rebrand the information and distribute it to their constituents. A similar program, the National Kidney Disease Education Program (NKDEP), exists for populations at greatest risk of kidney disease.
Dr. Rodgers discussed the NIDDK budget for fiscal year (FY) 2014–2015. On January 17, 2014, an omnibus appropriation partially restored funds that were lost in FY 2013. The omnibus appropriation was preceded by the Federal shutdown in October 2013 and sequestration earlier in the year, and thus it provided welcome relief. The NIH budget was $29.15 billion (B) in FY 2013 and $30.15B in FY 2014. The NIDDK budget was $1.83B in FY 2013 and $1.881B in FY 2014. Dr. Rodgers explained that the pay lines were restored to 2012 levels, and he emphasized the importance of ensuring that the “pipeline does not leak.” Early stage investigators experience a higher funding rate than established investigators. The President’s budget requested a $12 million (M) increase for NIDDK in FY 2015.
Samuel Dagogo-Jack, M.D., M.S., MBBS, Professor of Medicine, and Director, Division of Endocrinology, Diabetes and Metabolism, A. C. Mullins Chair in Translational Research, University of Tennessee Health Science Center
Dr. Gaillard introduced the keynote speaker, Dr. Samuel Dagogo-Jack. Dr. Dagogo-Jack is Professor of Translational Research and Medicine and Chief of the Division of Endocrinology at the Tennessee Health Science Center in Memphis. He graduated from University of Audubon in Nigeria and completed his residency training at the Royal Victoria Infirmary, University of Newcastle in the United Kingdom. He is a certified member of the Royal College of Physicians. He completed a postdoctoral fellowship in Endocrinology at the University of Washington School of Medicine in St Louis. His research interests include the interaction of genetic and environmental factors, the regulation of metabolism, and the mechanisms of diabetes complications, including hypoglycemia. He is currently the PI for four NIH-funded research studies and has published more than 200 papers.
Dr. Dagogo-Jack thanked the meeting organizers and all the attendees. He said that he attended the first NMRI meeting 14 years ago and has been coming ever since. He began the keynote lecture by explaining the meaning of the word “kindling”: a metaphor for the increase in response to small stimuli, similar to the way small burning twigs can produce a large fire. He intends to use the word in its rhetorical meaning of sparking enthusiasm. There is almost a religious angle to the word enthusiasm: inspiration or possession by the divine presence of God.
The creation and transmission of knowledge represents an ancient human tradition. Dr. Dagogo-Jack showed a picture of the Ebers Papyrus—a 5,000-year-old text—that included a hieroglyphic description of diabetes. Imhotep, a physician who lived 3,000 years ago in Memphis, Egypt, was a physician, philosopher, and advisor to the Pharaoh. In those times, access to knowledge and education was carefully guarded and limited to a privileged few. The rituals to access knowledge in ancient cultures are evidence that all ancient cultures understood the power of knowledge. The triumph of education liberalization in the United States is that it makes knowledge and education accessible to the majority of the population.
Dr. Dagogo-Jack provided another example, that of Hasan Wazzan. He was born in 1445 in Granada and educated as a scientist in Fez, Morocco. He was captured by Italian pirates off the coast of Africa and taken as a slave to Pope Leo X. Impressed with his knowledge and high intelligence, the Pope converted and baptized him Wazzan. Adopting the name Leo Africanus, Wazzan led a free intellectual life in Italy as a professor of African Studies and returned to Africa in 1529. In 1550, he published an encyclopedic description of the landscape, rivers, flora, and fauna of Africa. Leo’s magnus opus, Della Descrittione Dell’Africa, is divided into nine volumes that provide a treasure of information. Thus, stressed Dr. Dagogo-Jack, the creation and dissemination of knowledge represent an ancient culture.
Despite a description of diabetes that goes back 5,000 years in the Ebers Papyrus, there was no effective treatment until the modern era. Around 1921, Charles H. Best (a medical student) working with Frederick Banting, John McCleod, and James Collip (the chemist) at the University of Toronto successfully extracted and purified insulin from animal pancreas. That work eventually led to a Nobel Prize being awarded to the Toronto scientists. The discovery of insulin launched the first successful treatment for diabetes that has saved millions of lives.
The Institute of Medicine report, Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care, identified disparities across numerous healthcare settings, disease areas, and clinical services. Disparities in diabetes prevalence and treatment are particularly notable. Type 1 diabetes is more prevalent in Caucasians, whereas type 2 diabetes is more prevalent in other populations. Both are subtended by the interaction between genes and environment, and both involve failure of beta-cell function.
Based on current examination of dozens of genes that confer diabetes risk, racial/ethnic differences in type 2 diabetes prevalence cannot be explained easily by genetic mechanisms. Furthermore, the health disparities in the complications of diabetes (including amputations) cannot be explained by genetics either. For example, disparities in access to healthcare and health education appear to explain a good part of the disparities in amputation rates. In the Kaiser Permanente health system, where all participants were insured and had access to appropriate care, amputation rates were similar among Whites, Blacks, and Latinos with diabetes.
The root of disparity centers on a triangle with vertices of the patient, workforce, and system. The patient must be health literate, adherent, and self-efficacious. The workforce must display competency and eliminate implicit biases. The system must be accessible to all, offer the same standards for everybody, and be responsive to feedback.
Diversity in the biomedical workforce is necessary to redress disparities and enable a broader representation of the at-risk populations. Dr. Dagogo-Jack gave the example of the Framingham study, which was comprised of 94.7 percent European Americans and thus not representative. These types of noninclusive study cohorts do not generate data that are generalizable. Currently ongoing trials are more representative, but enrollment of African Americans in clinical trials varies significantly. Dr. Dagogo-Jack provided an example of a trial that he led addressing the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC). The POP-ABC participants were African-American or Caucasian subjects whose parents had type 2 diabetes. The recruitment target was reached by conducting strategic outreach to churches and community gatherings. Recruitment and outreach methods varied in efficacy for African Americans versus Caucasians. Advertising was a major source of recruitment for Caucasian men, but community outreach was more than twice as effective for African-American men. The study found that there was no disparity in the rate of progression from normal glucose to prediabetes among Caucasian and African-American offspring of diabetic parents. Yet, national survey data show marked racial disparities in the prevalence of diabetes. The question, then, is why there was an enrichment of diabetes prevalence in the African-American group compared to Caucasians. Similar to the findings of the POP-ABC, another study (the Diabetes Prevention Program) previously had found that the rates of progression from prediabetes to type 2 diabetes were similar for all racial/ethnic groups, and interventions for diabetes prevention were equally effective in all racial/ethnic groups. Dr. Dagogo-Jack thus stressed that focusing on people with a family history of diabetes, rather than broad targeting based on race, would be a more efficient strategy for diabetes prevention.
Dr. Dagogo-Jack’s keynote address fueled the workshop participants’ enthusiasm for biomedical research. He next addressed the question of how to translate this enthusiasm into action. He emphasized the importance of finding mentors. The mentor should have a strong academic record to provide the necessary guidance through the paths navigated in the course of a career. Mentoring is a long-term relationship. With respect to underrepresented minorities, there is a virtuous cycle of diversity. Mentors from underrepresented minorities tend to attract minority students and trainees, who will in turn become productive scholars and eventually develop into independent researchers and mentors.
After finding a mentor, it is necessary to consider research ideas. To generate ideas, Dr. Dagogo-Jack recommended using checklists, as explained in Atul Gawande’s book The Checklist Manifesto. Another approach is to start with a strong research question. Factors to consider include choosing a common medical condition (for which it is easy to recruit subjects); playing to the strengths of one’s institution (in terms of available equipment and expertise); personal passion for the field; generous funding opportunities; finding a unique niche close to the mentor’s field; identifying unmet needs; and staying attuned to emerging areas. It also is useful to collaborate with experts. In choosing research areas, it is as important to consider “unanswered questions” as it is to examine “unquestioned answers,” thus balancing observation with experiment.
Dr. Dagogo-Jack listed traits necessary for success, such as intellect, ambition, originality, and collaborative work style. A solid hypothesis is necessary, but one should not become too attached. It is necessary to measure something—preferably something that counts. He gave the example of death rates from coronary heart disease by race and ethnicity. Although there are many factors connecting blood pressure to blood glucose, he does not believe that all of the factors that matter are being measured.
Challenges faced by young scientists include receiving funding and getting published. Funding sources include Federal agencies (e.g., the National Science Foundation [NSF] and NIH), nongovernmental organizations, and industry. Race matters—African Americans are less likely to win NIH R01 grants. Dr. Dagogo-Jack noted that among the top-scored grants, there is no racial disparity; however, the racial/ethnic disparity in application rate is striking. Dr. Dagogo-Jack emphasized that it is necessary to apply for more grants to win more awards. African Americans are four times less likely to reapply if they were unsuccessful on the first round—this is not evidence of systematic discrimination. Rather, he encouraged participants to apply in larger volumes and to respond to critiques and reapply. Other factors that will increase the likelihood of winning a grant include working at one of the top 30 NIH-ranked institutions; record of previous funding; number of publications; number of citations; and participation in an NIH review committee.
As for the challenges of getting published, Dr. Dagogo-Jack recommended visualizing the papers that will come out of a research project well in advance, and writing the introduction as well as the sections on materials and methods. He recommended “becoming a writer,” and exhorted the participants not to “sit on data.” He also warned participants to expect that their manuscripts will be rejected often, but not to take it personally—instead, to regroup and resubmit. He shared a journal rejection letter for a breakthrough paper by Drs. Solomon Berson and Rosalyn Yalow. Notably, the discovery of radioimmunoassay described in that rejected paper won a Nobel Prize for Dr. Yalow. Thus, rejection happens to everyone.
Dr. Dagogo-Jack concluded by reminding the participants that “it is an honor and privilege to be involved in the creation and dissemination of knowledge. Research provides the opportunity to join the ancient guild of seekers of truth and givers of knowledge. Society needs more creative minds to advance the human species, to solve problems, and to write the next chapter in the future of biomedicine.”
A participant asked about the absence of disparity in the prevalence of prediabetes in African Americans and Caucasians. He suggested that the study might have been truncated too soon to see a separation between the groups. Perhaps studies should be followed for longer than the typical 5 years. Dr. Dagogo-Jack agreed. The participant also asked about the endpoint that was measured for assessing pre-diabetes. Dr. Dagogo-Jack said that blood sugar is important, but other biomarkers such as high-density lipoprotein (HDL) and low-density lipoprotein (LDL) would be useful as well.
Dr. Tiffany Beckman remarked, from a graph in Dr. Dagogo-Jack’s presentation, that American Indians have the highest rates of cardiovascular mortality. She also noted that American Indians are not represented in the graph showing the success rates for winning a first R01 grant. Dr. Dagogo-Jack explained that American Indians were not represented on that slide because their numbers were too small to scale with the rest of the graph.
Another participant, a surgeon, asked about the physiology of diabetes. In his practice, he conducts bariatric surgery. He noted that within a week, his patients become nondiabetic, even though they have not lost weight after the surgery. Their genes did not change. This is important data and may lead to prevention strategies. Dr. Dagogo-Jack responded that the rapid improvement in patients after bariatric surgery could be explained by several possible mechanisms. He suggested that the change is most likely due to the conditioning and lifestyle changes that occur in the prebariatric phase. The conditioning must be successful before a surgeon will operate. This conditioning includes a drastic portion restriction, which is effective whether or not the patient subsequently undergoes surgery. The difference is that the portion restriction is more sustainable in the group that undergoes bariatric surgery.
The participant remarked that surgeons are largely absent from research because the clinic is more lucrative. Surgeons are not encouraged to do research or to write grants. Research for surgeons is relegated to a “hobby.” He asked Dr. Dagogo-Jack how to maintain a culture of research in the field of surgery. Dr. Dagogo-Jack remarked that on the broader issue of research, society seems to be shifting to an anti-intellectual bent. Academic health centers currently run operating budgets of about $700M, and approximately 70 percent of the budget is derived from clinical income, unlike previous decades where research funding formed a larger part. Thus, surgeons are encouraged to operate; there is limited time and energy for scholarly pursuits. The compensation incentives have shifted, and research is not rewarded as much as clinical work. Dr. Dagogo-Jack suggested that this situation will self-correct when the United States is threatened with a second-place status in research.
A participant noted the importance of churches as a place to conduct outreach and health education. The participant gives talks at local churches, and the response is overwhelming—church members want to learn about diabetes and periodontal disease, among other topics. One problem, however, is that young people are dissociating themselves from organizations. Nevertheless, at the high-school level, there is an overwhelming response; it is critical to cultivate high school and undergraduate programs in science.
UPDATE ON National Institute on Minority Health and Health DisparitIES (NIMHD) FUNDING OPPORTUNITIES

Joyce Hunter, Ph.D., Deputy Director, NIMHD, NIH

Dr. Hunter described the mission of the NIMHD and highlighted three programs that may be of particular interest to the NMRI audience. The mission of NIMHD is to (1) plan, review, coordinate, and evaluate all minority health and health disparities research and activities of the NIH; (2) conduct and support research in minority health, with particular emphasis on cardiovascular disease (CVD), diabetes, and cancer; (3) promote and support training of a diverse research workforce; (4) translate and disseminate information about minority health and health disparities; and (5) foster innovative collaborations and partnerships.

NIMHD extramural programs fall into four major categories: (1) trans-disciplinary and translational research; (2) basic, social, and behavioral research; (3) science education and research training; (4) research capacity building and infrastructure. The research funded by the NIMHD is comprised of three broad types: (1) basic and applied biomedical research (funded by an R01 mechanism); (2) social and behavioral health research and policy research on minority health and health disparities (also funded by an R01 mechanism); and (3) community-based participatory research (CBPR; funded by R24 grants). The NIMHD separates basic and applied research from social and behavioral research. The Institute’s research portfolio is diverse, including such areas as obesity, AIDS, diabetes, and others. All of the research is performed in the context of health-disparate populations, usually on conditions that disproportionately affect underrepresented minorities.
The basic and applied biomedical research encompasses fundamental biological mechanisms, but also emphasizes the development of new therapies to eliminate health disparities, as well as clinical and translational research on the etiology and physiology of disease. There is interest in pharmacogenomics and personalized medicine. In the second category—social, behavioral, health services, and policy research on minority health and health disparities—research includes the social and behavioral determinants of health and disease, the clinical efficacy and effectiveness of preventive interventions, the examination of understudied health conditions, the impact of health policies on health disparities, and health services research. The CBPR program is funded through R24 grants and consists of three independent phases, including a 3-year research planning grant; a 5-year intervention research grant; and a 3-year dissemination research grant. It is not necessary to apply for each stage successively; for example, if a completed study needs to be disseminated through outreach activities, it is possible to apply directly for the 3-year dissemination research grant.
Dr. Hunter introduced the NIH Loan Repayment Program (LRP), which is designed to retain early-career health professionals. Many early-career biomedical scientists have extravagant professional debt. The LRP provides an opportunity to engage in biomedical research with a 2-year commitment in exchange for paying educational loans. The program is designed to retain health professionals in pediatric research, contraception and infertility research, and health disparities research, as well as clinical researchers from disadvantaged backgrounds. The health disparities research loan repayment can apply to any disease or condition, provided that the topic is relevant to health disparity issues. The amount of loan repayment is $35,000, plus taxes and interest, per year for 2 years. An extramural clinical research LRP for individuals from disadvantaged backgrounds is renewable with an annual deadline of December 1. Since its inception, the NIMHD has supported more than 3,400 loan repayment recipients.
Basic eligibility criteria include possessing a doctoral level degree and not being a current employee of the Federal government. The LRP allows recipients to consolidate all student loans (undergraduate and graduate). Between 2012 and 2013, there were 65 NIMHD LRP recipients conducting research in diabetes, metabolic syndrome, digestive disorders, obesity, and kidney and urological disorders. LRP recipients have studied the following topics, among others:

  • In basic and applied research areas, they have studied the association of adipokines in CVD and the neural correlates of food reward in American Indian women.

  • In clinical and translational research, they have addressed obesity disparities through a CBPR mechanism and investigated the genetic mechanisms of HIV infection in Latinos.

  • In social and behavioral science research, they have studied the social determinants of racial disparities in chronic kidney disease.

  • In health services research, they have examined the role of patient-provider communication in illness management for diabetes.

LRP recipients are very competitive, become independent investigators at a higher rate than their colleagues, and develop into leaders in their fields. There is a need to increase the diversity of the biomedical research workforce, and the LRP provides a pathway to accomplish this goal.

A participant asked whether there must be a racial difference at the level of fundamental molecular mechanisms to be supported by an NIMHD grant. Dr. Hunter said that there does not need to be a difference at the level of the molecular mechanism, but that the study must address a health disparities problem. The case should be made in the background section of the grant.
Dr. Richard White said that he has benefited from the LRP program since 2009. He explained that the LRP allowed him to focus on reducing his personal debt. He expressed gratitude for the program and encouraged others to apply. He is currently a health disparities researcher focusing on health literacy and the improvement of diabetes outcomes. He would like to study not just adult or pediatric populations in the context of obesity prevention, but also family-based interventions. Dr. Hunter reiterated that all studies are eligible for NIMHD funding, provided they are conducted in a health-disparate population.
Dr. Regina Simms mentioned that she also benefited from the LRP, but her grant was not renewed. She asked for clarification about whether it would be advantageous to represent herself as an independent or mentored researcher in the application, and she asked at what level a researcher is considered independent. Dr. Hunter replied that it is always helpful to partner with consultants and experts. She advised the mentored approach.
Another recipient of the LRP said it was very useful for keeping him financially stable during his time as a junior faculty member. He noted, however, that those working for the U.S. Department of Veterans Affairs (VA) are not eligible because it is part of the Federal government. He then asked a question about basic and applied research sections: Are those grants reviewed by special-emphasis panels based on the scientific expertise that is required? Dr. Hunter said that these grants are reviewed internally and are not sent to NIH’s Center for Scientific Review (CSR).
Another participant asked whether it is necessary to have funded research at the time of application. Dr. Hunter explained that applicants need preliminary data to use as the basis for the research plan. A participant who received the LRP said that at the time that he applied, he had full funding already, but the funding expired during the LRP period.
Dr. Hunter clarified that applicants are eligible only if the loan represents more than 20 percent of the applicant’s income. A participant asked whether there are LRPs for those who do not meet the 20-percent eligibility criteria. Dr. Hunter said that such programs do exist.
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