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| 15645 | Reflecting on a Remarkable 2019 | Your browser does not support JavaScript or it is not enabled.hr.fancy { overflow: visible; /* For IE */ padding: 0; border: none; border-top: medium double #333; color: #333; width: 66%; text-align: center; } hr.fancy:after { content: "§"; display: inline-block; position: relative; top: -0.9em; font-size: 1.5em; padding: 0 0.25em; background: white; } .card { /* Add shadows to create the "card" effect */ box-shadow: 0 4px 8px 0 rgba(0,0,0,0.2); transition: 0.3s; } /* On mouse-over, add a deeper shadow */ .card:hover { box-shadow: 0 8px 16px 0 rgba(0,0,0,0.2); } .modalBodyText { text-align: left; } area { cursor: pointer; } .verticalScroll { overflow-y: scroll; } December 26, 2019Christopher P. Austin, NCATS director, looks back on an exciting year of accomplishments. Watch his video message.Highlights of NCATS' Accomplishments in 2019By joining forces with a diverse set of partners, we advanced the conversation on important issues to accelerate scientific progress. Collaboration is integral to our approach for breaking down barriers in the translational science process, as illustrated in these highlights from 2019. View the slideshow. | NCATS Year in Review - 2019 | NCATS Year in Review - 2019 | ||||||
| 15513 | A Promising Step in the Fight Against Lethal Childhood Brain Cancers | Confocal micrograph of diffuse intrinsic pontine glioma (DIPG) cells, grown from patient cells, in culture. (Shawn Gillespie, Monje Lab, Stanford Medicine)November 20, 2019Scientists find promising drug combination against lethal childhood brain cancersStudies in cell and animal models reveal insights into cancer cells’ vulnerability that could lead to new strategies against brain cancersResearchers have devised a new plan of attack against a group of deadly childhood brain cancers collectively called diffuse midline gliomas (DMG), including diffuse intrinsic pontine glioma (DIPG), thalamic glioma and spinal cord glioma. Scientists at the National Institutes of Health, Stanford University, California, and Dana-Farber Cancer Institute, Boston, identified a drug pair that worked together to both kill cancer cells and counter the effects of a genetic mutation that causes the diseases.The researchers showed that combining the two drugs – panobinostat and marizomib – was more effective than either drug by itself in killing DMG patient cells grown in the laboratory and in animal models. Their studies also uncovered a previously unrecognized vulnerability in the cancer cells that scientists may be able to exploit to develop new strategies against the cancer and related diseases. The results were published November 20 in Science Translational Medicine.Matrix screening delivers insights, increases optionsDMGs are aggressive, hard-to-treat tumors that represent the leading cause of brain cancer-related death among U.S. children. DMGs typically affect a few hundred children a year between ages 4 to 12; most children die within a year of diagnosis. Most cases of DMG are caused by a specific mutation in histone genes. Histones are protein complexes in the cell nucleus. DNA wraps around histones to form chromatin, which packages DNA in the nucleus. How DNA winds and unwinds around histones is influenced by enzymes, including histone deacetylases. These enzymes add or remove chemical tags, which indirectly controls if genes are turned on or off.In an earlier study, Stanford neuro-oncologist Michelle Monje. M.D., Ph.D., and her colleagues showed that panobinostat, which blocks key histone deacetylase enzymes, could restore the DIPG histone function to a more normal state. While panobinostat is already in early clinical testing in DIPG patients, its usefulness may be limited because cancer cells can learn to evade its effects. So Monje’s team wanted to identify other possible drugs – and combinations of them – that could affect the cancer.“Very few cancers can be treated by a single drug,” said Monje, a senior author of the study who treats children with DIPG and other diffuse midline gliomas. “We’ve known for a long time that we would need more than one treatment option for DIPG. The challenge is prioritizing the right ones when there are thousands of potential options. We’re hopeful that this combination will help these children.”Monje and the National Cancer Institute’s (NCI) Katherine Warren, M.D., now at Dana-Farber Cancer Institute and Boston Children’s Hospital, collaborated with Craig Thomas, Ph.D., and his colleagues at the NIH’s National Center for Advancing Translational Sciences (NCATS). Thomas and his team used NCATS’ drug screening expertise and matrix screening technology to examine drugs and drug combinations to see which ones were toxic to DIPG patient cells.NCATS’ robotics-enabled, high-throughput screening technologies enable scientists to rapidly test thousands of different drugs and drug combinations in a variety of ways. Scientists can examine the most promising single drugs and combinations, determine the most effective doses of each drug and learn more about the possible mechanisms by which these drugs act.The NCATS researchers first studied the effects of single approved drugs and investigative compounds on DIPG cell models grown in the laboratory from patient cells. They focused on agents that could both kill DIPG cells and cross the brain’s protective blood-brain barrier, a necessity for a drug to be effective against DIPG in patients. The team then tested the most effective single agents in various combinations.“Such large, complex drug screens take a tremendous collaborative effort,” said Thomas, also a senior study author. “NCATS was designed to bring together biologists, chemists, engineers and data scientists in a way that enables these technically challenging studies.”While there were multiple, promising outcomes from these screens, the team focused on the combination of histone deacetylase inhibitors (like panobinostat) with drugs called proteasome inhibitors (such as marizomib). Proteasome inhibitors block cells’ normal protein recycling processes. The panobinostat-marizomib combination was highly toxic to DIPG cells in several models, including DIPG tumor cell cultures that represented the main genetic subtypes of the disease and mice with cells transplanted from patient tumors. The combination also reduced tumor size in mice and increased their survival. A similar response was found in spinal cord and thalamic DMG models developed from cells grown in culture from patient cells.Mechanisms at playThe screening studies also provided important clues to the ways the drugs were working. Building on these data, the collaborative team subsequently conducted a series of experiments that showed the DIPG cells responded to these drugs by turning off a biochemical process in the cell’s mitochondria that is partly responsible for creating ATP, which provides energy to cells. The drug combination essentially shuts down tumor cell ATP production.“The panobinostat-marizomib drug combination exposed an unknown metabolic vulnerability in DIPG cells,” said first author Grant Lin, Ph.D., at Stanford University School of Medicine. “We didn’t expect to find this, and it represents an exciting new avenue to explore in the development of future treatment strategies for diffuse midline gliomas.”Plans are underway for clinical trials of the drug combination and of marizomib alone.“Many drugs that we test have multiple effects on DIPG cells,” said Warren, a senior study author. “Panobinostat, for example, inhibits a specific enzyme, but it has other mechanisms working in tumor cells that may contribute to its effectiveness. We’re still trying to understand the various Achilles heels in these cancer cells. This work is an important step in translating our preclinical data into patients.”Monje stressed the panobinostat-marizomib combination might be an important component of a multitherapy strategy, including approaches that harness the immune system and those that disrupt factors in the tumor microenvironment that the glioma cells depend on to grow. Like Warren, Monje emphasized the need to better understand how drugs target and impact the DIPG cells’ vulnerabilities.“Our work with NCATS showed the need to gather more preclinical data in a systematic, high-throughput way to understand and prioritize the strategies and agents to combine,” Monje said. “Otherwise we’re testing things one or two drugs at a time and designing clinical trials without preclinical data based on hypothesized mechanisms of action. We want to move past this guesswork and provide preclinical evidence to guide clinical decisions and research directions.” Lin added, “The idea is to get as many effective tools as possible to work with that can have an impact on patients.”The research was funded by Alex’s Lemonade Stand Foundation, Izzy’s Infantry Foundation, McKenna Claire Foundation, Unravel Pediatric Cancer, Defeat DIPG Foundation, ChadTough Foundation, N8 Foundation, Kortney Rose Foundation, Cure Starts Now Foundation and the DIPG Collaborative, Sam Jeffers Foundation, Lyla Nsouli Foundation, Abbie’s Army Foundation, Waxman Family Research Fund, Virginia and D.K. Ludwig Fund for Cancer Research, National Institute for Neurological Disorders and Stroke (R01NS092597) and NIH Director’s Common Fund (DP1NS111132), Maternal and Child Health Research Institute at Stanford, the Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood Diseases, The DIPG All-In Initiative and the NCATS and NCI intramural programs.About the National Center for Advancing Translational Sciences (NCATS): NCATS conducts and supports research on the science and operation of translation — the process by which interventions to improve health are developed and implemented — to allow more treatments to get to more patients more quickly. For more information about how NCATS is improving health through smarter science, visit https://ncats.nih.gov.About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.NIH…Turning Discovery Into Health® | A Promising Step in the Fight Against Lethal Childhood Brain Cancers | A Promising Step in the Fight Against Lethal Childhood Brain Cancers | ||||||
| 15477 | Collaboration to Enhance Naloxone Distribution in Rural Areas | CONsiDER Project Team Opioid misuse in the United States has reached pandemic proportions and represents a significant public health problem, with rural areas being disproportionately affected. To address this health crisis, a range of strategies are being implemented, including the use of naloxone, an opioid antagonist medication. Pharmacists are the most accessible health care providers in rural and medically underserved areas, and recent legislative efforts in many states have increased access to naloxone through statewide standing orders and pharmacist prescriptive authority. Nevertheless, multiple barriers still hinder effective pharmacy-based naloxone distribution. To address this translational gap, The University of New Mexico Clinical and Translational Science Center (CTSC) (PrincipaI Investigator: Richard Larson, M.D., Ph.D.; Project Co-Directors: Ludmila Bakhireva, M.D., Ph.D., M.P.H., and Theresa Cruz, Ph.D.) led a collaborative Project CONsiDER with Clinical and Translational Science Award (CTSA) Program hubs at Tufts University (Thomas Stopka, Ph.D., M.H.S.) and the University of Minnesota (Laura Palombi, Pharm.D., M.P.H., M.A.T., AE-C) to develop an innovative and sustainable model to increase the dispensing of naloxone by community pharmacists practicing in rural and underserved areas. The UNM CTSC became interested in leading this research because New Mexico has one of the highest rates of opioid overdose in the country. Additionally, New Mexico is a largely rural state, ranking fifth in size among the 50 states, with a total population of 2.1 million. New Mexico is also ethnically diverse, with a population that is 49.1% Hispanic and 10.9% American Indian. The UNM CTSC partnered with the University of Minnesota and Tufts University Clinical and Translational Science Institutes because of their aligned interests in addressing the opioid epidemic in rural areas. The study focused on dissemination and implementation science, which addresses a T3 “translational gap” between scientific discovery and routine practice. The goal was to improve public health by improving the health care delivery system in rural communities. Specifically, we aimed to increase naloxone dispensing by pharmacists by adapting an evidence-based intervention to the local context in New Mexico, Minnesota and Massachusetts, and then implementing the intervention, which focused on pharmacist training regarding naloxone and naloxone dispensing. We first engaged community stakeholders in each state, including community pharmacists, the state Departments of Health, the state Boards of Pharmacy and professional organizations. These partners collaborated with us to identify core elements of the pharmacy education materials, as well as state-specific modifications (e.g., information about state pharmacy laws regarding naloxone dispensing) to bolster local relevance to pharmacy staff and customers. Their input informed the adaptation and implementation of the intervention in different contexts. We then pilot tested the intervention at community pharmacies in each state. The training focused on pharmacological information regarding naloxone, communication skills, strategies for reducing stigma and guidance regarding how to operationalize naloxone dispensing. The trainings were conducted in person, at the pharmacy, with a follow-up visit to address site-specific implementation challenges. It captured both pharmacists and pharmacy technicians and included staff- and patient-oriented materials. Baseline and follow-up surveys were conducted with participating staff to assess changes in naloxone distribution, as well as changes in attitudes, self-efficacy and intent with regard to naloxone distribution. Several challenges were encountered during the study, including staff turnover, need to secure management support for participation, travel distances for the research teams, variable work schedules for participants and time for participation. The research team employed several strategies to mitigate these challenges. A pharmacist on the research team sought regional approval from pharmacy chain managers for the program. Additionally, the team engaged pharmacy students to help with pharmacy operations at training sites under the guidance of a College of Pharmacy preceptor. This allowed the pharmacy to continue functioning while pharmacists and technicians participated in the training. The team also needed to be flexible regarding when to conduct the trainings to fit into pharmacy schedules. Lastly, although travel distances to rural areas remain a barrier to intervention implementation, several strategies are recommended to mitigate the challenge. These include training pharmacist trainers in different regions of the state, developing online materials to supplement the in-person training and training multiple pharmacies in a region on the same trip. Although there was some variability by state, overall accomplishments of the project included establishing the feasibility of implementation in rural communities, increasing knowledge and self-efficacy regarding naloxone and naloxone dispensing, and minimizing stigma associated with opioid overdose prevention (Figure 1). Preliminary results also indicate substantial increase in naloxone dispensing post-intervention in participating sites. Pharmacists participating in the study also reported on the benefits of the intervention. One participant, addressing the communication skills component of the training, stated, “I think the training made me rethink how to address naloxone with patients.” Another pharmacist commented, “I really enjoyed the role play. It helped me apply information in a realistic way.” Pharmacists also noted the importance of including technicians in the trainings, because technicians play a leading role in interactions with pharmacy customers. Because of the successful outcomes of the pilot study, the New Mexico Department of Health is supporting the New Mexico research team in the dissemination and evaluation of the intervention throughout the state. This model demonstrates a successful testing of a novel intervention via the CTSA network followed by a statewide dissemination supported by local agencies. This multistate collaborative approach among three CTSA Program hubs directly addressed NCATS’ goal of “a more integrated and collaborative national network.” By leveraging the resources of the CTSA Consortium, the CONsiDER Project developed a robust implementation model tested in differing contexts (e.g., differing naloxone policies, unique opioids, differential access to care, and varied population demographics) that is scalable throughout the country through the CTSA consortium. For questions about the CONsiDER Project and training materials, please contact Dr. Ludmila Bakhireva at lbakhireva@salud.unm.edu or Dr. Theresa Cruz at thcruz@salud.unm.edu. | The University of New Mexico CTSC led Project CONsiDER has developed a sustainable model to increase the dispensing of naloxone in rural and underserved areas, see details. | Collaboration to Enhance Naloxone Distribution in Rural Areas | The University of New Mexico CTSC led Project CONsiDER has developed a sustainable model to increase the dispensing of naloxone in rural and underserved areas, see details. | Collaboration to Enhance Naloxone Distribution in Rural Areas | ||||
| 15489 | Addressing Health Disparities and Improving Rural Health | Figure 1. Location of clinics in the WWAMI region The Institute of Translational Health Sciences is strongly committed to addressing health disparities and improving rural health across the Washington, Wyoming, Alaska, Montana and Idaho (WWAMI) region. A key mechanism for this work is the effort of the WWAMI region Practice and Research Network (WPRN), which supports collaboration between primary care practices and academic researchers on research that improves the health and well-being of patients in their communities and enhances primary care clinical practice. The WPRN is a practice-based research network of more than 80 primary care clinics across 34 organizations in the five-state WWAMI region. These clinics include community health centers, private and academically affiliated practices, and government-operated clinics—49 of which are rural serving, 30 are Community Health Centers or Federally Qualified Health Centers, and 21 are Critical Access Hospital–affiliated rural health clinics. These clinics are spread throughout the WWAMI region, which covers 27% of the land mass of the United States and includes vast rural areas with both minority and underserved populations [Figure 1]. The University of Washington’s School of Medicine serves the WWAMI region, with more than 95% of acceptances coming from applicants in the region. The WPRN was formed in this environment in partnership with the WWAMI region educational programs in the Department of Family Medicine, specifically the Family Medicine Residency Network (FMRN). Programs in the FMRN were interested in increasing their research activities, and the WPRN provided an opportunity for regional practices and residency sites to participate and collaborate in translational research. WPRN Annual Meeting Because medical needs in rural areas are largely met by primary care, to improve the health of rural communities it is critical to engage the primary care practices that serve them. With this goal in mind, the WPRN developed a research model that includes site clinical research champions supported by a coordinating center that facilitates participation by small rural practices. The WPRN has focused on geographic diversity in an effort to ensure that rural health needs are recognized and that rural populations can participate in cutting-edge research. The WPRN coordinating center has recruited diverse champions and focused on engagement strategies that can succeed in resource-limited rural settings. Multiple opportunities for inclusion are incorporated, ranging from annual meetings, a survey research panel, and engagement projects that focus on issues driven by the community. With this infrastructure and these relationships, within the past 10 years, the WPRN has been able to support more than 80 projects, 60 publications and 200 grant applications related to rural health. One of the most visible successes from this work is the development of Data QUEST, a shared electronic health record network containing data from more than 150,000 patients. These patients span more than 500 providers and 25 clinics, 60% of which are rural or rural-serving and support observational studies and pragmatic clinical trials. Another major accomplishment is Team-Based Safe Opioid Prescribing, a research project that implemented the Six Building Blocks Program approach for more selective and cautious opioid prescribing for chronic non-cancer pain across 20 rural health clinics. The Six Building Blocks Program provides a roadmap for redesigning and improving a clinic’s management of patients who are on long-term opioid therapy for chronic pain. This program began as an observational study of best practices that then developed into an intervention rigorously tested in rural practices that has been widely disseminated. The number of patients using long-term opioid therapy decreased by 14% over 15 months in the Six Building Blocks clinics—from 2,065 to 1,776. Additionally, the proportion of patients on high-dose opioids (≥ 100 MED daily) decreased 20% within the program, from 11.8% to 9.6%. Clinicians and staff across the rural-serving clinics enrolled in Six Building Blocks reported that the program improved their work-life experience and their ability to provide high-quality care. They reported increased confidence and comfort in providing care, enhanced collaboration and teamwork, and improved relationships with patients. The Six Building Blocks program is now being disseminated regionally and nationally, with dozens of practices impacting thousands of patients through grants and contracts with the National Institute on Drug Abuse, the Washington State Department of Health, the Agency for Healthcare Research and Quality and the Olympic Community of Health. WPRN Annual Meeting In achieving its success, the WPRN has surmounted a number of barriers, none so difficult as the wide distances between primary care practices. To prevent geographic limitations from causing issues with clinic integration and engagement, the WPRN makes heavy use of telework strategies to foster and maintain a high level of engagement across the network. The WPRN also hosts an annual full-day conference in Seattle to bring site champions together face-to-face, conducts webinars to onboard new studies across the network, and—most importantly—ensures that all research results are returned to the clinics for studies on which they have collaborated. Another common barrier to inclusion of remote care facilities in research is combating the expectations of urban researchers. Frequently, resource-rich research institutions assume incorrectly that rural centers will be unable to carry out research for budgetary or feasibility reasons. Strategies implemented through the WPRN, including novel remote recruitment plans and virtual focus groups, have shown that this presumption need not be the case. Misconceptions about the capacity and quality of rural research centers are a significant roadblock for many institutions that attempt to conduct research on rural health and heath disparities. The WPRN has shown over the years that rural communities and practices are accomplished in their own right and are not simply to be considered as smaller versions of urban communities and practices. Rural settings have their own ecosystems and contexts that are critical to understand and consider when conducting collaborative research. Strong relationships and bidirectional partnerships make this work possible. It cannot be stressed enough that translational research should not be unidirectional; the academic institution does not always bring discovery to rural communities. There is an enormous amount of innovation in rural communities, and Clinical and Translational Science Award (CTSA) Program hubs have the opportunity and the obligation to identify those health innovations, empower researchers in the field, and provide tools and resources so that each CTSA can perform research with rural communities, rather than on rural communities. To learn more about the Institute of Translational Health Sciences, please visit www.iths.org. For more information about the WWAMI region Practice and Research Network, please visit www.iths.org/community/partners/crn/wprn/. For more information on the Six Building Blocks Program, please visit www.improvingopioidcare.org. | The WPRN is a practice-based research network of more than 80 primary care clinics across 34 organizations in the Washington, Wyoming, Alaska, Montana and Idaho (WWAMI) region. | Addressing Health Disparities and Improving Rural Health | The WPRN is a practice-based research network of more than 80 primary care clinics across 34 organizations in the Washington, Wyoming, Alaska, Montana and Idaho (WWAMI) region. | Addressing Health Disparities and Improving Rural Health | ||||
| 15486 | The Rural Health Research Support Network | Evidence is lacking on best practices for community-engaged translational research in rural communities with underserved, multiethnic and vulnerable populations. Living in rural America is associated with health disparities that are not seen in urban areas (e.g., higher rates of accidental injury, cardiovascular disease, cancer and suicide).1 Rural populations are poorer and have less access to health care and mental health services. According to the U.S. Census Bureau, 19% of the country’s population is rural.2 In New Mexico, however, 60% of the population lives in rural communities. Furthermore, 30 out of the 33 counties are designated Health Professional Shortage Areas.3 These vulnerable rural populations need to be represented in clinical and translational research, but methods to engage rural providers and community populations in translational research are not well defined. Rural health disparities affect people across the nation; the Rural Health Research Support Network (RHRSN) was developed to have a broader impact than focusing solely on New Mexico. This network includes multiple Clinical and Translational Science Award (CTSA) Program hubs across the United States with a goal of building research collaborations to address rural health priorities and accelerate clinical and translational research best practices in rural communities. The network aims to deliver rapid-response, best-practice methodology to conduct translational research in rural, underserved, multiethnic populations. The objective of the RHRSN is to support multisite studies in rural populations, test best practices for rural community engagement, and disseminate lessons learned to the larger CTSA collaborative and the public. Current core partners in the RHRSN are the Universities of New Mexico, Kansas, Kentucky, North Carolina, and Utah. Housed at the UNM Clinical and Translational Science Center (CTSC), the RHRSN program manager and national point of contact coordinates the committee and committee meetings, responds to inquiries, facilitates network collaborations, and serves as the research manager for local RHRSN projects. The network offers numerous services to assist with multisite rural health research, including consultation and training, connecting with communities, integrating special populations, mixed-methods data collection and analysis, capacity building, information dissemination, project management, research coordination, regulatory support, medical and laboratory tasks, and Spanish-English interpretation and translation. As expected, working with numerous institutions and people presents challenges. In the beginning of the network, the RHRSN program manager at the UNM CTSC. had to coordinate busy schedules, align visions, and determine services and associated fees. Now that the network and service core are established, the administrative lead for the RHRSN continues to experience difficulty in reaching out to investigators who may be interested in using RHRSN; identifying projects that work for multiple researchers with different interests, disciplines, schools and regions; coordinating busy schedules; and identifying and receiving funding. RHRSN Project Team The network has had notable successes. Twenty faculty and staff members nationwide are involved in the oversight of network activities and developing partnerships and expanding rural health research across our states. Through these key players, the RHRSN has received expressions of interest in potential collaborations from more than 60 researchers from across our network universities and beyond. Five other projects associated with the RHRSN are in development that will study diabetes prevention, cancer survivorship, social determinants of health, opioid stewardship and precision medicine. The first RHRSN feasibility project is being implemented across four states, looking at Acceptance and Commitment Therapy as a behavioral approach to treating chronic non-cancer pain and reducing chronic opioid use. North Carolina PI Jacquie Halladay, M.D., M.P.H., says, “The needs of rural citizens and the medical practices that serve them are great and often unique. With the many pressing issues of the day, we must continue to work collaboratively to understand how to enhance outcomes for people living in rural settings. The network infrastructure allowed us to engage in a pilot project across four CTSA Program hubs…This allowed for the creation of many new processes in an applied manner. For instance, we were able to learn how to use a single Institutional Review Board [IRB] (the first one at UNM), how to enhance our skills in file sharing, and use of survey instruments using REDCap. The pilot work has taught us many important lessons that should enhance our efficiency at conducting a larger multisite effectiveness trial.” The RHRSN network encourages collaboration with more investigators, CTSA Program hubs and universities. If you are interested in learning more about RHRSN or connecting with the network, please visit our website and email the RHRSN Program Manager, Heidi Rishel Brakey, at hrishelbrakey@salud.unm.edu. The RHRSN network looks forward to working with you! References National Rural Health Association: www.ruralhealthweb.org/about-nrha/about-rural-health-care U.S. Census Bureau (2010). American Fact Finder. Urban and Rural; Universe: Total population; 2010 Census Summary File 1. factfinder2.census.gov. Kaufman, A., W. Powell, C. Alfero, et al. 2010. “Health Extension in New Mexico: An Academic Health Center and the Social Determinants of Disease.” Ann Fam Med 8 (1): 73–81. | The Rural Health Research Support Network | The Rural Health Research Support Network | ||||||
| 15483 | Peer-based Retention Of people who Use Drugs in Rural Research | PROUD-R2 Research Team The Peer-based Retention Of people who Use Drugs in Rural Research (PROUD-R2) study addresses the epidemics of opioid prescribing, injection drug use, overdose and infectious disease transmission in rural America. Investigators in Ohio, Oregon and Kentucky had been working on local projects funded by the National Institute on Drug Abuse’s National Rural Opioid Initiative. Over time, they recognized commonalities in their states’ rural experiences with the opioid epidemic and the challenges of recruiting and retaining people in rural areas for research participation. The team sought to leverage the tightknit relationships and social connectivity of rural communities as an untapped resource for increasing access to drug use treatment interventions in rural America. Challenges in recruitment and retention are common in substance use research, particularly in rural communities, and threaten the validity of clinical trials. The PROUD-R2 study tests strategies to improve the retention of people who use drugs (PWUD) in research in rural communities, and fosters participation of rural participants into clinical trials. Historically, research methods to study PWUD were crafted in urban settings and cannot simply be imported to rural communities, which differ demographically, socioculturally and in infrastructure. The study aims to identify optimal strategies for retaining people with opioid use disorder in clinical research in rural America. This study leverages the National Rural Opioid Initiative infrastructure in rural Oregon and Appalachian Kentucky and Ohio, using existing study pathways to recruit PWUD in rural settings. In rural settings, people who use drugs or who are in recovery can successfully reach and engage their peers in treatment, but their potential to improve participation and retention in clinical trials is largely unexplored. The PROUD-R2 study tests an innovative peer-retention approach that combines elements of peer navigator models for outreach with the structure of peer recruitment (i.e., respondent-driven sampling) to improve study retention. Study participants, who are recruited from the three states’ existing National Rural Opioid Initiative studies, are randomized to one of two arms: One group receives the standard strategy for study retention (i.e., outreach from the research staff by text message and phone call reminders); the other group watches a brief training video on how to encourage friends and people with whom they use drugs to stay engaged in the study (i.e., retention training) and receives incentives for helping to keep people in the study. Through qualitative interviews, discrete choice experiments, and follow-up surveys at six and 12 months following enrollment, PROUD-R2 explores perceptions of research participation and retention, assesses preferences and willingness to participate in future clinical trials, and examines the impact of the peer intervention on retention. Each study site collaborates with local staff and local community advisory boards comprised of people with direct experience of the current opioid epidemic. The peer retention training video—where peers serve as actors—was developed by Comagine Health, a health care consulting firm, with input from the community advisory boards. PROUD-R2 also benefits from collaboration with Dr. Hannah Cooper of Emory University and Dr. Vivian Go at The University of North Carolina at Chapel Hill, who oversee qualitative data collection and analysis. The first year of the project laid the groundwork for a successful three-state collaboration. Study teams in Oregon, Kentucky and Ohio harmonized their data collection instruments and locator forms, established a data coordinating center, and conducted a formative quantitative survey to sharpen the focus of the intervention. A national training is scheduled to bring the study teams together in person to standardize data collection procedures and study retention strategies. PROUD-R2 recognizes the power of peers to connect with PWUD. Peers can build rapport and trust with people who use drugs as they discuss the personal and societal benefits of participating in clinical trials. A quote from one of the study’s participants sums up the potential impact of peers and overarching goal of our project: “…if I went to treatment I would much rather talk to someone that's been there, done that, than to talk to someone that's never experienced what I've experienced. You know, someone that knows where I'm coming from. Instead of someone trying to teach me about what I've already been through and has no idea.” In the coming years, PROUD-R2 will continue to discover how to improve retention of difficult-to-reach populations in rural areas of the country most impacted by opioid use disorder. | The Peer-based Retention Of people who Use Drugs in Rural Research (PROUD-R2) study addresses the epidemics of drug use and infectious disease transmission in rural America. | Peer-based Retention Of people who Use Drugs in Rural Research | The Peer-based Retention Of people who Use Drugs in Rural Research (PROUD-R2) study addresses the epidemics of drug use and infectious disease transmission in rural America. | Peer-based Retention Of people who Use Drugs in Rural Research | ||||
| 15480 | Addressing Diseases of Despair in a Rural Community | Andrea Murray, Community-Engaged Research Project Manager, leads a discussion to collect qualitative data in the second phase of Penn State’s Translation of Despair and Healthcare project. Penn State Clinical and Translational Science Institute is working to understand the effects of social and economic issues on health in rural communities. These issues have contributed to a decline in American life expectancy. Many rural Pennsylvania communities are experiencing unique challenges related to the health of residents. Deaths related to heart and liver diseases, diabetes, accidental opioid overdose, and suicide are rising in American small towns. These are referred to as “diseases of despair.” Research suggests that diseases of despair are related to social and economic conditions. For example, Pennsylvania has seen the peak and decline of several industries, including coal and steel. “We want to learn more about how diseases like depression and substance abuse develop because of these social and economic conditions,” Lawrence Sinoway, M.D., principal investigator and director of the institute, said. “We want to learn how they affect the communities that surround us and understand whether we can predict who will develop these diseases. Most importantly, can we treat and prevent them?” Sinoway developed an interest in this topic after the release of a paper by economists Case and Deaton (PNAS, 2015), who helped propose the concept of diseases of despair. The institute secured an administrative supplement (NOT-TR-18-18-022) from NCATS for a pilot program. This program identified hot spot communities with higher rates of disease of despair diagnoses in Pennsylvania and will now learn what factors may be contributing to these diseases to develop potential interventions. The institute partnered with Highmark Health Enterprise Analytics Data Science Research to identify hot spots for further analysis to determine potential interventions. The Data Science Research Group, a part of Highmark Health insurance company, supported the project through its expertise in machine learning and artificial intelligence. “Our partnership with Highmark Health was essential to the success of our efforts,” Sinoway said. “They identified trends in their commercial insurance, Affordable Care Act, Medicare and Medicaid plans that we incorporated into Penn State datasets acquired through a variety of related efforts.” The findings of this work include the following: Rates of diseases of despair were significantly higher in 2018 than they were in 2009 for both men and women across nearly every age group. The odds of having a disease of despair diagnosis in 2018 were 7.4 times higher among Medicaid members than among members of other types of plans. Rising rates of diseases of despair are driven not only by substance-related disorders. The rate of alcohol-related disorders has increased significantly among women ages 18–74 and among men ages 35 and older. The rates of diagnosis of suicide ideation/behaviors have significantly increased for both men and women of all age groups. Among those younger than age 35, the incidence of suicide ideation/behavior diagnoses has tripled. Neighborhood-level socioeconomic indicators are extremely valuable in predicting which areas are likely to experience high rates of diseases of despair. These findings can ultimately guide targeted prevention and intervention efforts. “We have seen great value in collaborating with Penn State to understand and address the challenges facing rural communities,” Curren Katz, Ph.D., director of data science research at Highmark Health, said. “Both Highmark and Penn State have a deep interest in improving health care for members and patients. Our partnership has enhanced understanding and will help improve health in the communities we serve.” A second phase of the project, led by Danny George, MS.c., Ph.D., associate professor of humanities and public health sciences and a co-investigator on the project, is working with health care professionals and community organizations in the hot spot communities to explore what contributors to poor health are missed and why. Understanding how clinics and organizations can adapt to this emerging health crisis and what opportunities exist for better training will be explored through focus groups. “This problem is particularly troubling in poorer rural areas, such as Appalachia,“ George said. “These communities have suffered, for example, from decades of loss of industry, loss of social safety nets, reduced union membership, stagnant wages, reduced access to higher education and the infiltration of opioid drugs.” Jennifer Kraschnewski, M.D., M.P.H., associate professor of medicine and public health sciences, and a co-investigator on the project, helped identify local partnerships both within and outside the health system. “Rural Pennsylvania has been particularly impacted by these diseases,” Kraschnewski said. “Our Clinical and Translational Science Institute is eager to partner with our surrounding rural communities to address the rising rate of diseases of despair.” The institute is currently exploring additional projects and initiatives to build on this initial research. “This is important work,” Sinoway said. “These are issues that affect our friends, families and neighbors. Penn State is positioned to work with our neighboring communities and health systems to have a positive effect on these challenges.” References Anne Case, Angus Deaton. Rising midlife morbidity and mortality, US whites. Proceedings of the National Academy of Sciences Dec 2015, 112 (49) 1 | Penn State Clinical and Translational Science Institute is working to understand the effects of social and economic issues on health in rural communities. | Addressing Diseases of Despair in a Rural Community | Penn State Clinical and Translational Science Institute is working to understand the effects of social and economic issues on health in rural communities. | Addressing Diseases of Despair in a Rural Community | ||||
| 15474 | The Appalachian Translational Research Network | The Appalachian region encompasses 205,000 square miles with more than 25 million residents. The region stretches from New York to Mississippi, including all of West Virginia and parts of Alabama, Georgia, Kentucky, Maryland, North Carolina, Ohio, Pennsylvania, South Carolina, Tennessee and Virginia. Nearly half of the region is rural, and many rural Appalachian counties experience severe hardship, including high rates of poverty, high unemployment, struggling educational systems and limited health infrastructure.1 Coinciding with these hardships are health disparities that are among the worst in the nation. Appalachian communities have the highest rates of mortality in the United States for seven of the 10 leading causes of death—heart disease, cancer, chronic obstructive pulmonary disease, injury, stroke, diabetes and suicide—not to mention the highest rates of highest rates of death due to drug overdose.1,2 Although residents of most U.S. counties have experienced an increase in life expectancy in recent decades, this has not been the case in many Appalachian counties. In fact, since 1980 there has been a decrease in life expectancy for residents of Central Appalachian Kentucky. Recognizing that a team approach was critical to addressing the significant health challenges of their respective Appalachian populations, the Center for Translational Science Award (CTSA) Program hubs of the University of Kentucky and The Ohio State University formed the Appalachian Translational Research Network (ATRN) in 2010. The ATRN has since expanded to include CTSA Program hubs from the University of Cincinnati, Pennsylvania State University and Wake Forest University, as well as West Virginia University, which is funded with an Institutional Development Award for Clinical and Translational Research (IDeA-CTR). Two CTSA-affiliated universities, Marshall University and Ohio University, are also ATRN members. Currently representing eight member institutions from across multiple states, the ATRN continues to expand its membership with the goal of having representation from universities across the expanse of Appalachia. Under the guidance of an executive leadership team and with representation from each member institution, the ATRN facilitates inter-institutional sharing of research expertise, experiences and resources to promote improved health in our Appalachian communities. To support synergy, the leadership team meets monthly to share general information, discuss opportunities for collaboration and plan future collaborative opportunities. A quarterly ATRN newsletter is published and disseminated widely to anyone with interest who signs up to receive it, regardless of institutional affiliation. The newsletter serves to spotlight ATRN members’ research activities, funding opportunities, and inter-institutional training and seminar opportunities. Each newsletter also showcases Appalachian community partners. Also important to supporting synergy is the Network’s annual Summit. Hosted each year by a different member institution, the ATRN Summit provides a venue for disseminating findings from scientific investigations supported through the ATRN, as well as other research relevant to Appalachia. The Summit provides a forum for investigators to network, not only with scientists from other ATRN-affiliated universities, but with community members who are also invited to participate and who find in the Summit a forum to disseminate information and evidence relevant to the health of their communities. Another key component of the Summit is the opportunity for scientific development. Predoctoral and postdoctoral students, as well as early career investigators across the member institutions who are interested in research relevant to Appalachian health issues, are encouraged to present their research and, in turn, receive feedback and guidance from more seasoned investigators. Foundational to the continuing stability and growth of the network, the ATRN leadership has developed organizational bylaws. Furthermore, all ATRN activities are guided by our vision statement, “Health equity across Appalachia,” and mission statement, “To improve health outcomes across Appalachia by fostering collaborative inter-institutional and community-academic research partnerships.” Responsive to our mission, we support multiple research initiatives. Among these is an inter-institutional pilot program. With funding provided by ATRN member institutions, we issue an annual Request for Applications to support collaborative research involving investigators from two or more ATRN institutions. Through this annual pilot program we have funded multiple studies over the years, resulting in a return on investment of $19:$1 (Figures 1 and 2). More recently, a Community-Academic Partnership pilot program has been implemented to support research that engages investigators from two or more ATRN member institutions in partnership with community organizations from their respective sites. Pivotal to the success of the ATRN is the support provided by NCATS and the National Institute of General Medicine, as well as the principal investigators of the member institutions’ funded CTSA and IdeA-CTR centers and affiliated universities. As a result of this investment, the ATRN is able to continue to promote research collaborations and to enhance synergy across ATRN institutions to positively impact health across Appalachia. For more information about the ATRN, please contact Gia Mudd-Martin, Ph.D., M.P.H., R.N. at Gia.Mudd@uky.edu. References 1 PDA, Inc., The Cecil G. Sheps Center for Health Services Research, and the Appalachian Regional Commission. Health Disparities in Appalachia. Published August 2017. www.arc.gov/assets/research_reports/Health_Disparities_in_Appalachia_August_2017.pdf. Accessed October 1, 2019. 2 East Tennessee State University and NORC at the University of Chicago. Issue Brief: Health Disparities Related to Opioid Misuse in Appalachia. Practical Strategies and Recommendations for Communities. Published April, 2019. www.arc.gov/assets/research_reports/HealthDisparitiesRelatedtoOpioidMisuseinAppalachiaApr2019.pdf. Accessed October 1, 2019 | The Appalachian Translational Research Network is the supported by NCATS to promote research collaborations in order to positively impact health across Appalachia. | The Appalachian Translational Research Network | The Appalachian Translational Research Network is the supported by NCATS to promote research collaborations in order to positively impact health across Appalachia. | The Appalachian Translational Research Network | ||||
| 15330 | NIH funds new <i><b>All of Us</b></i> Research Program genome center to test advanced sequencing tools | A HudsonAlpha team member prepares samples for DNA analysis. (HudsonAlpha Institute for Biotechnology)October 18, 2019HudsonAlpha awarded $7 million to expand national health dataset with uncharted genetic variants.The All of Us Research Program has selected the HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, to evaluate the use of leading-edge DNA sequencing technologies that could someday improve diagnosis and treatment of many diseases, both common and rare. The National Center for Advancing Translational Sciences (NCATS) is funding the project with $7 million over one year. All of Us and NCATS are parts of the National Institutes of Health.“All of Us will provide one of the world’s most robust platforms for precision medicine research, with a broad range of data to drive new discoveries,” said Eric Dishman, All of Us director. “Through this partnership with NCATS, we’ll be able to offer approved researchers an even greater depth of genetic information than originally planned, making the resource even more valuable for them and the diverse communities we seek to help.”With this award, HudsonAlpha will use long-read whole genome sequencing technologies to generate genetic data on about 6,000 samples from participants of different backgrounds. Long-read sequencing analyzes DNA in larger segments than standard (short-read) sequencing technologies, exposing genetic variations that may otherwise go undetected. These variations include different types of alterations to the genetic structure, such as duplication, deletion or rearrangement of the building blocks that uniquely make up one’s genome and set it apart from others. Everyone has thousands of these genetic variations, most with little known effect. However, researchers are learning more about how some genetic variants underlie certain health conditions or, conversely, increase disease resistance. Understanding the genetic underpinnings of health and disease will help researchers identify more targeted interventions in the future.This project will allow researchers to better determine the value of long-read sequencing and its strengths and limitations in exploring more elusive parts of the genome. Combined with the 1 million whole genome sequences the program already plans to deliver over the next several years, this additional infusion of genetic information will provide the research community with the largest collection of genomic structural variation data and clinical data ever produced.“Because long-read sequencing can reveal genetic changes associated with rare diseases, this project is an opportunity to assess and potentially refine the technology for advancing research across the many diseases for which there is no treatment,” said Christopher P. Austin, M.D., NCATS director. “This project illustrates the power of data and technology to accelerate the translation of knowledge into improved health.”The HudsonAlpha team, led by Shawn Levy, Ph.D., brings significant experience in large-scale sequencing projects and in genetic studies on inherited disorders as well as complex conditions, including autism, diabetes, cancer, schizophrenia, degenerative neurological disease and amyotrophic lateral sclerosis (ALS).“We look forward to collaborating with the other All of Us genome centers and the rest of the consortium on this exciting effort,” said Dr. Levy. “Contributing long-read sequencing data to reveal additional structural variants will enable the scientific community to study human diversity on a tremendous scale. Appreciating the impacts of all types of genetic variation will further unravel the genetic, environmental and behavioral influences of health.”About the All of Us Research Program: The mission of the All of Us Research Program is to accelerate health research and medical breakthroughs, enabling individualized prevention, treatment, and care for all of us. The program will partner with one million or more people across the United States to build the most diverse biomedical data resource of its kind, to help researchers gain better insights into the biological, environmental, and behavioral factors that influence health. For more information, visit www.JoinAllofUs.org and www.allofus.nih.gov.About the National Center for Advancing Translational Sciences (NCATS): NCATS conducts and supports research on the science and operation of translation—the process by which interventions to improve health are developed and implemented—to allow more treatments to get to more patients more quickly. For more information about how NCATS is improving health through smarter science, visit ncats.nih.gov.About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov. | NIH funds new All of Us Research Program | NIH funds new All of Us Research Program | ||||||
| 15298 | Questions and Answers About OTA-19-009 | Administrative How do applicants find this funding opportunity announcement (FOA) in ASSIST? When are applications due? Are open source licenses, such as Affero Public Licenses or GNU Public Licenses, compliant with respect to Data and Software Sharing? Should applicants who plan to coordinate with other programs submit a support letter with assurances regarding coordination? If applicants provide a list of collaborators and references who may verify a history of collaborative scientific efforts, is there additional value in obtaining more detailed support letters from prior collaborators? Should a bibliography be included? If so, is it part of the two-page limit for the project plan? Should applications be uploaded into ASSIST as a single PDF? Can NCATS provide more information regarding the reviewers and their background with the Translator program? What criteria will the reviewers use? Is there a font requirement for figure legends? Under "Application Content", the FOA lists five topics that should be addressed in the Summary Vision Statement. What instructions will reviewers be given with regard to these topics? In addressing the Summary Vision Statement topics, is there any disadvantage or prohibition with addressing these topics in other sections of the application if that alternate organization is clearer? Do applicants need to submit sub-award paperwork for the first submission Can a researcher apply in collaboration with an NIH Intramural Research Program scientist? If so, does he or she need a letter of support from the NIH scientist? When applying in ASSIST, if the answer to question #8 regarding Human Subjects involved is “yes” (not a clinical trial), do applicants need to add the optional human subjects form, or will this information be requested at a later time? May existing Clinical and Translational Science Awards (CTSA) Program awardees submit competitive proposals on their own, without having been part of the previous phases and prototypes. Is there another group with whom such grantees should talk about partnering on a proposal? Where can applicants find guidelines for the Data Sharing and Collaboration Plan above and beyond the instructions found in the FOA? Do applicants need to include sections (e.g., Sharing Model Organisms or Genome-Wide Association Studies)not involved in the proposed project? Are applicants required to submit letters of support from the PI and Co-PI if the PI and Co-PI are from the applicant institution? How does NCATS define "collaborator" with regards to Letters of Support? As subcontractors we use contractors that will contribute to the proposed project. Do those contractors also need to provide a letter of support to the submitting institution, or can we speak to their contributions in our letter as the sub-award site? What is the page limit for Letters of Support? Regarding font sizing, a set of NIH guidelines say that although the font size for the proposal should be 11 pt, “Smaller text in figures, graphs, diagrams and charts is acceptable, as long as it is legible when the page is viewed at 100%.” We would like to reduce the font size used in our tables to 10 pt. Can you verify that this is permissible here? Is there a page limit on the personnel table? Where should literature references be included in the application, and should they be provided in PDF format? If an applicant institution plans to provide a Letter of Support that indicates the institution’s efforts and the efforts of its contractors, do the contractors need to submit separate Letters of Support or may the institution submit one Letter of Support encompassing the collective efforts of the institution and its affiliates? If an application includes any large tables, may a 10-pt. font be used in those tables? Milestones and/or Budget As a reminder to all applicants, the budget and budget detail is not weighted in the review process. If additional information is required it will be requested in pre-award negotiation. Are applications expected to provide milestones and/or detailed budgets for the $50k “continuation” after the (successful) prototype presentation? The Project Milestones section asks for annual milestones and associated costs (per milestone) in up to three pages. Should this include both the segment 1 and segment 2 milestones, or just segment 2? How should the one-page budgets for each segment be formatted? Is the total award project period for both first and second award segment periods combined up to five years? Is there any specific period limit for each award segment period? If an applicant’s direct costs fall outside of the expected range, should the applicant submit the application with an out-of-range budget, or should the applicant adjust the direct costs to fit the expected range? What is the duration of the first budget segment (fixed cost of $34,000 and the additional $50,000)? Will the second funding segment be 12 months in duration? Do the expected budget ranges stated in the FOA include the funds provided in the first funding segment? Should applicants submit budgets and work plans beyond 2020 since the FOA indicated an award project period of up to five years? Will applicants have to submit a separate application for the second funding segment? Is there a preference for how a second funding segment budget section is submitted? Will answers be provided to questions sent in for NOT-TR-19-028? Should applicants propose milestones that are appropriate for that full first funding segment Since the prototype presentations by first segment awardees will occur half-way through the first funding segment, is the expectation that applicants will have completed 50% of their first segment milestones? Is a budget breakdown required for the $50K component? Page 10-11 only seem to request a breakdown for the $34K direct costs of segment 1 and then also for segment 2 with no mention of the $50K component. In one section of the Q&A it indicates to provide a detailed budget for only for segment 2 and in another section it indicates to provide a detailed budget only for the first year of funding. Is my understanding correct that the milestone section should have the detailed budget for segment 2 and the budget section should include the detailed budget for the first year of funding? Is it permissible to ask for hardware/dedicated servers or will NCATS provide Amazon Web Services (AWS) or equivalent cloud services? Should applicants budget $50,000 in Segment 1 or Segment 2? Personnel Under personnel, it states, “While there is no minimum effort level required for the principal investigator (PI) or multiple principal investigators (MPIs), due to the intensive nature of this program, after the first segment of the award, a minimum of two team members with a minimum of 50% effort each is expected. Do not include salaries here. For the first segment, please indicate which personnel will be involved and their level of effort during that period.” Does this indicate that the PIs/MPIs are expected to be at a minimum of 50% effort, or just two team members? For a funded, multiple-MP application (one prime award with multiple sub-awards), will all PIs, co-PIs and MPIs be recognized in the Notice of Award (NoA) and in the Research Portfolio Online Reporting System (RePORT)? Does NCATS require detail of the personnel proposed? Should this be included as application content for Personnel, Budget or both? For the first funding segment, should only one PI be involved, or should the full team be included from the beginning? If an applicant would like to submit to multiple components, may he or she identify resources as key on multiple, separate applications? Are NIH intramural scientists with an interest in this field eligible to apply? How can they participate? Are applicants required to include information on each team member (i.e., what they're going to contribute, why they're the right person for the work, etc.) as part of the budget justification? Is such information necessary, and/or should this be worked into the personnel table? Components - General Where do user interface/interactive components from current Translator initiatives fit into the FOA component framework? How can applicants reuse/build on the Subject Matter Expert graphs and demonstrator diseases that have been studied and elaborated during the feasibility assessment phase? What framework does NCATS envision for the sustainability of Translator knowledge sources (old and new)? Is an application about modeling knowledge in Translator for subsequent data loading a priority for a knowledge provider? Is there a list of data types that are required for submission, or do the applicants propose a set of attributes? Do private data need to be provided, or can public data be used? Is there a specified list of clinical data/attributes that should be included? Are cancer data permissible? What is the definition of artificial intelligence (AI)-ready? The FOA states that Knowledge Providers will be domain-specific and that Autonomous Relay Agents will need to traverse this federated system of Knowledge Providers. Is this a requirement of Autonomous Relay Agents? Or, is this an example only? Would a large knowledge graph that an Autonomous Relay Agent queries be an acceptable application? Are there technical requirements on Knowledge Providers and Autonomous Relay Agents, in terms of interfaces that must be implemented or technologies that must be used? Alternatively, will all requirements be determined by the Standards and Reference Implementation component? Some applicants may be having difficulty deciding which component is the best fit for their group. What guidance can NCATS provide for making this decision? The FOA lists several objectives for each program component. Is an application for a given component required to address every stated objective? Will different data types that only pertain to cancer but are not applicable to other diseases be admissible? How will existing user interfaces (UIs) be included in the program? Does NCATS expect a page on Previous Work Examples only for Applicants for the Translator Standards and Reference Implementation component? Components - Knowledge Providers If there is a knowledge type that currently does not exist from the Translator feasibility stage, how do we best integrate the new knowledge type? As an exploratory component? Should applicants with data from multiple scientific domains submit separate applications for each knowledge provider? Is there an expectation that a funded knowledge provider will create an application program interface (API) to allow other services access? Is that expected to happen during the first segment of the project? Can a knowledge provider application focus on scalable technologies and approaches or should knowledge providers focus on a specific domain? Components - Autonomous Relay Agents With respect to the scale and scope of Autonomous Relay Agents, will the Autonomous Relay System call an individual Autonomous Relay Agent and expect that Autonomous Relay Agent to perform end-to-end question answering? Or, is it acceptable to restrict the scope of individual Autonomous Relay Agents (e.g., enrichment of a gene list or filtering knowledge graphs by select criteria)? Are Autonomous Relay Agents defined by the interface that they implement, by some definition of their function, or simply by the idea that they will plug into an as-yet-undefined larger system (i.e., the Autonomous Relay System)? Is there a role for User Interfaces in the Autonomous Relay Agents components, either to pose queries, interpret results or collect user input mid-query? Or, will the User Interface be strictly within the domain of the Autonomous Relay System? Are autonomous relay agents expected to work with any knowledge provider? Is it possible that interactive Autonomous Relay Agent components intended for use by system developers to achieve specific software-development objectives (e.g., quality assurance), but not intended to be "the Translator user interface", are in scope for an Autonomous Relay Agent component application? Components - Standards and Reference Implementation Presumably, the Standards and Reference Implementation component is intended to function largely as a governance body, a technical research and development body, or an implementation body. However, is there a particular emphasis? If the Standards and Reference Implementation component is primarily governance related, what sort of prototype would be appropriate? It's hard to imagine a prototype for the Standards and Reference Implementation component. Can NCATS provide guidance? Administrative How do applicants find this funding opportunity announcement (FOA) in ASSIST? Applicants who are having ASSIST issues need to make sure that they are using OTA-19-009. When are applications due? Applications must be submitted through NIH’s ASSIST site by 5 p.m. local time on Nov. 15, 2019. Are open source licenses, such as Affero Public Licenses or GNU Public Licenses, compliant with respect to Data and Software Sharing? Yes. All software and other tools used for this project must be open source and publicly available at the time of application, and all software created during the project period must be made publicly available through program-directed source code repositories. Any software or library license leveraged by Translator tool(s) must support free and open source software development for the development phase as well as general production use. Should applicants who plan to coordinate with other programs submit a support letter with assurances regarding coordination? If an applicant’s plan is not reliant or dependent on the other program, a support letter is not required at the time of submission. Letters of support for all collaborators/other significant contributors, consultants and sub-award sites should be provided. If applicants provide a list of collaborators and references who may verify a history of collaborative scientific efforts, is there additional value in obtaining more detailed support letters from prior collaborators? No. Letters from former collaborators and references that are written for the sole purpose of endorsement should not be included and will not be considered during review. A list of previous collaborators (limited to one page) who may be contacted as references as to the applicants’ history of collaborative work on large-scale projects should also be included, as applicable. Should a bibliography be included? If so, is it part of the two-page limit for the project plan? The bibliography is optional and will not count against the page limit. Should applications be uploaded into ASSIST as a single PDF? Yes. Please submit all application content as a single text-readable PDF. Can NCATS provide more information regarding the reviewers and their background with the Translator program? The review of the written applications will be similar to a study section review panel in that it will be primarily composed of non-federal scientists. The reviewers are external to the program and NCATS. The Translator program will provide an orientation for the reviewers to conduct their evaluations independently. There will not be a meeting and NCATS is not seeking consensus. NCATS will make the first segment awards after the initial review, assessing the evaluation criteria including complementarity. This review will drive the results of the first segment awards. For the second funding segment, the prototype reviews will be conducted by NCATS. What criteria will the reviewers use? The reviewers will utilize the Program Component evaluation criteria and the Additional, Shared Evaluation Criteria found on page 8 of the FOA. Is there a font requirement for figure legends? All pages should be Arial 11-pt., single-spaced with 1-in. margins. Figure legends should be legible to reviewers. Under "Application Content", the FOA lists five topics that should be addressed in the Summary Vision Statement. What instructions will reviewers be given with regard to these topics? The Summary Vision Statement should summarize the content of the full application and will not be evaluated independently. Reviewers will be asked to evaluate applications using all materials provided by the applicant. In addressing the Summary Vision Statement topics, is there any disadvantage or prohibition with addressing these topics in other sections of the application if that alternate organization is clearer? Applicants should include a single page describing the summary vision statement. Applicants may also choose to expand upon these topics in other sections of the application. Do applicants need to submit sub-award paperwork for the first submission? Applicants who plan to include a partnering organization (collaborator/subcontract/subaward) should include this information in the application. If the partnering organization is key to the success of the activity proposed, a letter of support from the partnering organization should be included. The budget section does not require separate budget documentation from partnering organizations. The budget details should provide enough information for reviewers to understand the relationship between the funds being requested and proposed milestone activity. If any specific detailed budget documentation is required it will be requested during the pre-award negotiation. Can a researcher apply in collaboration with an NIH Intramural Research Program scientist? If so, does he or she need a letter of support from the NIH scientist? Intramural scientists are eligible to apply. Letters of support for all collaborators/other significant contributors, consultants and sub-award sites should be provided. If an applicant’s plan is not reliant or dependent on the other program, a support letter is not required at the time of submission. When applying in ASSIST, if the answer to question #8 regarding Human Subjects involved is “yes” (not a clinical trial), do applicants need to add the optional human subjects form, or will this information be requested at a later time? At this stage, answer “No” regarding Human Subject involvement. Should human subjects be involved at a later stage, information would be requested at that time. May existing Clinical and Translational Science Awards (CTSA) Program awardees submit competitive proposals on their own, without having been part of the previous phases and prototypes. Is there another group with whom such grantees should talk about partnering on a proposal? This is a full and open competition. Therefore, existing CTSA grantees may submit a competitive application with or without a partnering organization. Where can applicants find guidelines for the Data Sharing and Collaboration Plan above and beyond the instructions found in the FOA? Do applicants need to include sections (e.g., Sharing Model Organisms or Genome-Wide Association Studies)not involved in the proposed project? Applicants must include (in a single page) a plan for data sharing and a collaboration plan, which should address the requirement for open-source code deposition for the project. The plan needs to address only relevant data types and collaborations. Are applicants required to submit letters of support from the PI and Co-PI if the PI and Co-PI are from the applicant institution? If the PI and Co-PI are from the applicant institution, letters of support would not be necessary. How does NCATS define "collaborator" with regards to Letters of Support? Letters of support should be provided for anyone outside of the applicant institution who commits time or resources to the applicant institution’s project in a manner that would significantly impact the outcome of the proposed project. Successful applicants will work in a highly collaborative culture to build upon the work completed during the feasibility phase of the program. As subcontractors we use contractors that will contribute to the proposed project. Do those contractors also need to provide a letter of support to the submitting institution, or can we speak to their contributions in our letter as the sub-award site? Yes, collaborators include significant contributors, consultants and sub-award sites and Letters of Support should be provided. What is the page limit for Letters of Support? There is no page limit for letters of support. Regarding font sizing, a set of NIH guidelines say that although the font size for the proposal should be 11 pt, “Smaller text in figures, graphs, diagrams and charts is acceptable, as long as it is legible when the page is viewed at 100%.” We would like to reduce the font size used in our tables to 10 pt. Can you verify that this is permissible here? All pages should be Arial 11-pt., single-spaced with 1-in. margins. Figure legends should be legible to reviewers. Is there a page limit on the personnel table? There is no page limit. Where should literature references be included in the application, and should they be provided in PDF format? Please include literature references at the end of the application and submit the entire document as a single, text-readable PDF. If an applicant institution plans to provide a Letter of Support that indicates the institution’s efforts and the efforts of its contractors, do the contractors need to submit separate Letters of Support or may the institution submit one Letter of Support encompassing the collective efforts of the institution and its affiliates? Letters of support should be provided for anyone outside of the submitting institution (i.e., significant contributors, consultants and sub-award sites) committing time or resources to the project in a manner that would significantly impact the outcome of the proposed research. The applicant institution may submit the Letters of Support separately or collectively. NIH will advise applicant institutions if additional information is required. If an application includes any large tables, may a 10-pt. font be used in those tables? Yes. Applications may employ 10-pt. Arial in tables. Milestones and/or Budget As a reminder to all applicants, the budget and budget detail is not weighted in the review process. If additional information is required it will be requested in pre-award negotiation. Are applications expected to provide milestones and/or detailed budgets for the $50k “continuation” after the (successful) prototype presentation? The first segment has two parts with two different fixed price funding amounts ($34,000 or $35,500 plus $50,000 restricted). The $50,000 continuation of the first segment may be used to support preparation and participation in the kick-off meeting in late April including travel costs and for work during milestone and budget negotiations for the second funding segment. Release of these funds will be contingent upon the success of the applicant’s prototyped software presentation. If necessary, milestones for this period may be negotiated prior to release of the restricted funds. Awardees who do not receive invitations for the second award segment will not attend the kick-off meeting and the restricted funds will be de-obligated and returned to NCATS. The Project Milestones section asks for annual milestones and associated costs (per milestone) in up to three pages. Should this include both the segment 1 and segment 2 milestones, or just segment 2? While project milestones for the proposed project period and estimated costs associated with these milestones should be included, a detailed budget breakdown should be included for only segment 2. How should the one-page budgets for each segment be formatted? There is no specific format required for the budget submission. In the First Segment Award Milestones and Budget section, provide a two-page description of specific milestones to be completed during the first segment in order to demonstrate the value of the project’s expected contributions to Translator through prototyped software, along with all associated costs (total cost per milestone). NCATS will provide a fixed award of $34,000 in direct cost funds for this period. Applicants whose PIs have not received funding for work related to a Translator project in the past will receive an additional $1,500 direct costs (for a fixed total of $35,500 in direct cost funds) to defray the expenses associated with traveling to Bethesda, Maryland to present their prototype software in person. In the Project Milestones section, applicants should provide a description of annual milestones for the remainder proposed project period and associated costs (total cost per milestone) in up to three pages. While project milestones for the proposed project period and estimated costs associated with these milestones should be included for the full project period, a detailed budget breakdown should include only the first year of funding. Please note it is a requirement for applicants to submit a description of annual milestones and associated costs in the milestone section. The preference for the budget section is to be broken down by year. Is the total award project period for both first and second award segment periods combined up to five years? Is there any specific period limit for each award segment period? The duration of the first and second funding segments together will be up to 12 months. The full project period is up to five years. The first funding segment will be approximately four months. If an applicant’s direct costs fall outside of the expected range, should the applicant submit the application with an out-of-range budget, or should the applicant adjust the direct costs to fit the expected range? Budget ranges for the second segment were provided as a guide. There is no required minimum or maximum budget amount. Budgets for the second segment award must reflect the actual needs of the proposed project. What is the duration of the first budget segment (fixed cost of $34,000 and the additional $50,000)? The first funding segment will be approximately four months. In order to demonstrate the value of the project’s expected contributions to Translator through prototyped software, along with all associated costs (total cost per milestone). NCATS will provide a fixed award of $34,000 in direct cost funds for this period. Additionally, recipients of the first funding segment award will receive a restricted amount of $50,000 direct cost for continuation upon the success of the applicant’s prototype software presentation. If necessary, milestones for this period may be negotiated prior to release of the restricted funds. These funds may be used to support preparation and participation in the kick-off meeting in late April including travel costs and for work during milestone and budget negotiations for the second funding segment. Will the second funding segment be 12 months in duration? No. The duration of the first and second funding segments together will be up to 12 months. Do the expected budget ranges stated in the FOA include the funds provided in the first funding segment? No. The expected budget ranges are the direct costs NCATS is anticipating for the second funding segment, separate from the first segment funding. Should applicants submit budgets and work plans beyond 2020 since the FOA indicated an award project period of up to five years? While project milestones for the proposed project period and estimated costs associated with these milestones should be included, a detailed budget breakdown should include only the first year of funding. Will applicants have to submit a separate application for the second funding segment? The application should encompass the entire five-year project period with project milestones and estimated costs associated with these milestones. Is there a preference for how a second funding segment budget section is submitted? Please note that applicants are required to submit a description of annual milestones and associated costs. NCATS prefers that applicants break down the budget section by year. Will answers be provided to questions sent in for NOT-TR-19-028? The Translator team will provide anonymized questions and answers. Updates will be provided as questions are received; so, please check back here frequently. Should applicants propose milestones that are appropriate for that full first funding segment? The application should encompass the entire five-year project period with project milestones and estimated costs associated with these milestones. Since the prototype presentations by first segment awardees will occur half-way through the first funding segment, is the expectation that applicants will have completed 50% of their first segment milestones? The first segment has two parts with two different fixed price funding amounts ($34,000 or $35,500 plus $50,000 restricted). The application should include a two-page description of specific milestones to be completed during the first segment in order to demonstrate the value of the project’s expected contributions to Translator through prototyped software, along with all associated costs (total cost per milestone). Because the amounts provided for the first funding segment are fixed, the milestones will need to be associated with these fixed amounts. The milestones and associated costs should clearly identify which milestones are anticipated to be covered through each portion of the first segment. Is a budget breakdown required for the $50K component? Page 10-11 only seem to request a breakdown for the $34K direct costs of segment 1 and then also for segment 2 with no mention of the $50K component. A budget breakdown is not required for the $50,000 continuation. The first segment has two parts with two different fixed price funding amounts ($34,000 or $35,500 plus $50,000 restricted). The application should include a two-page description of specific milestones to be completed during the first segment in order to demonstrate the value of the project’s expected contributions to Translator through prototyped software, along with all associated costs (total cost per milestone). Because the amounts provided for the first funding segment are fixed, the milestones will need to be associated with these fixed amounts. The milestones and associated costs should clearly identify which milestones are anticipated to be covered through each portion of the first segment. The $50,000 continuation of the first segment may be used to support preparation and participation in the kick-off meeting in late April including travel costs and for work during milestone and budget negotiations for the second funding segment. In one section of the Q&A it indicates to provide a detailed budget for only for segment 2 and in another section it indicates to provide a detailed budget only for the first year of funding. Is my understanding correct that the milestone section should have the detailed budget for segment 2 and the budget section should include the detailed budget for the first year of funding? Correct. The duration of the first and second funding segments together will be up to 12 months. Is it permissible to ask for hardware/dedicated servers or will NCATS provide Amazon Web Services (AWS) or equivalent cloud services? NCATS will provide AWS or equivalent cloud services for the development phase. Should applicants budget $50,000 in Segment 1 or Segment 2? The first segment has two parts with two different fixed-price funding amounts ($34,000 or $35,500, plus $50,000 restricted). The $50,000 continuation of the first segment may be used to support preparation and participation in the kick-off meeting in late April, including travel costs and for work during milestone and budget negotiations for the second funding segment. Personnel Under personnel, it states, “While there is no minimum effort level required for the principal investigator (PI) or multiple principal investigators (MPIs), due to the intensive nature of this program, after the first segment of the award, a minimum of two team members with a minimum of 50% effort each is expected. Do not include salaries here. For the first segment, please indicate which personnel will be involved and their level of effort during that period.” Does this indicate that the PIs/MPIs are expected to be at a minimum of 50% effort, or just two team members? There is no minimum effort level required for the PI or MPIs on an application. A minimum effort of 50% is expected for any two team members. For a funded, multiple-MP application (one prime award with multiple sub-awards), will all PIs, co-PIs and MPIs be recognized in the Notice of Award (NoA) and in the Research Portfolio Online Reporting System (RePORT)? Yes. All applicants designated as Program Director/Principal Investigator (PD/PI) on a funded Multiple PD/PI application will be included in the NoA and NIH RePORT system. Applicants with multiple PIs are encouraged to submit an MPI Leadership Plan at the time of submission through the ASSIST program. However, the role type “co-PI” is not used by the NIH; therefore, individuals designated in that manner would not be included in either the NoA or RePORT. Please note that while multiple individuals may be named as Principal Investigator on a single application, any given investigator may be named as Principal Investigator on only one application. Does NCATS require detail of the personnel proposed? Should this be included as application content for Personnel, Budget or both? In the personnel section, please provide a table listing all personnel, including all to-be-named personnel, role on the project and percent of effort to be committed. While there is no minimum effort level required for the PI or MPIs, due to the intensive nature of this program, after the first segment of the award, a minimum of two team members with a minimum of 50% effort each is expected. Do not include salaries here. For the first segment, please indicate which personnel will be involved and their level of effort during that period. A detailed breakdown in the budget section is not required at the time of application submission. For the first funding segment, should only one PI be involved, or should the full team be included from the beginning? The application should describe your personnel for the full project period, but levels of effort may vary throughout the project. If an applicant would like to submit to multiple components, may he or she identify resources as key on multiple, separate applications? Yes. While there is no minimum effort level required for the PI or MPIs, due to the intensive nature of this program, after the first segment of the award, a minimum of two team members with a minimum of 50% effort each is expected. Please remember that an individual may be named as the PI on a single application; however, any given investigator may only be named as the PI on one application. Are NIH intramural scientists with an interest in this field eligible to apply? How can they participate? Intramural scientists are eligible to apply. NCATS will engage potential unfunded collaborators from within and outside NIH after awards have been issued. Are applicants required to include information on each team member (i.e., what they're going to contribute, why they're the right person for the work, etc.) as part of the budget justification? Is such information necessary, and/or should this be worked into the personnel table? In the personnel section of the application, include a CV or NIH biosketch for each of the key personnel who have committed to participating in the project if it is awarded. In the context of this program, it is especially important to highlight contributions of personnel to existing open source projects, standards and initiatives, as well as evidence of ability to work collaboratively. In the personnel section, please provide a table listing all personnel, including all to-be-named personnel, role on the project and percent of effort to be committed. While there is no minimum effort level required for the PI or MPIs, due to the intensive nature of this program, after the first segment of the award, a minimum of two team members with a minimum of 50% effort each is expected. Do not include salaries here. For the first segment, please indicate which personnel will be involved and their level of effort during that period. Components - General Where do user interface/interactive components from current Translator initiatives fit into the FOA component framework? Development of the Translator user interface is not included in the scope of the FOA. How can applicants reuse/build on the Subject Matter Expert graphs and demonstrator diseases that have been studied and elaborated during the feasibility assessment phase? The feasibility assessment phase demonstrated that Translator can accelerate translational research efforts in a manner that is fully transparent and open source. The next phase will continue to fill gaps in data and knowledge used, reduce Translator’s dependence on manual analysis, and increasing the breadth of data and speed with which users are able to uncover meaningful results to inform or generate hypotheses. What framework does NCATS envision for the sustainability of Translator knowledge sources (old and new)? The work funded through this FOA will be open source and publicly available; therefore, such resources could be further supported by any interested party. Is an application about modeling knowledge in Translator for subsequent data loading a priority for a knowledge provider? Applicants should address each of the program component objectives. In addition to reviewing the component objectives, using the component evaluation criteria also may provide more clarity. NCATS strongly encourages all applicants to closely review the component and shared evaluation criteria. Is there a list of data types that are required for submission, or do the applicants propose a set of attributes? Efforts during the feasibility phase resulted in an API standard known as the Reasoner Standard API. Like current knowledge providers (see the list of Translator knowledge providers at smart-api.info for examples), awardees should expect that their services will be invoked by other Translator tools, such as autonomous relay agents, at all stages of the program. Do private data need to be provided, or can public data be used? Data sharing is essential for expedited translation of research results into knowledge, products and procedures to improve human health; consequently, all software and other tools used for this project must be open source and publicly available at the time of application. Furthermore, all software created during the project period must be made publicly available through program-directed source code repositories. Any software or library license leveraged by Translator tool(s) must support free and open source software development for the development phase as well as general production use. Is there a specified list of clinical data/attributes that should be included? Knowledge Providers will seek out, integrate and provide high-value, AI-ready data sources within a specific scope of knowledge relevant to Translator. All components will aid in the planning and implementation of data and software standards for Translator. As an example of the integration of underutilized data, three major academic healthcare institutions within the Translator program created open clinical knowledge sources (Columbia Open Health Data, from Columbia University; Integrated Clinical and Environmental Exposures Service, from University of North Carolina; and Clinical Profiles, from Johns Hopkins University) to draw on patient data from electronic health records without compromising patient privacy and enabled incorporation of clinical knowledge into basic research knowledge graphs. This is only one example of the power of removing barriers to data integration and allowing for connections between seemingly incongruous sources of data. Efforts during the feasibility phase resulted in an API standard known as the Reasoner Standard API. Like current knowledge providers (see the list of Translator knowledge providers at smart-api.info for examples), awardees should expect that their services will be invoked by other Translator tools, such as autonomous relay agents, at all stages of the program. Are cancer data permissible? NCATS focuses not on specific diseases, but on what is common among them. Data types that are applicable across different diseases would be valuable for Translator. What is the definition of artificial intelligence (AI)-ready? AI-ready data are consumable by the autonomous relay agents and autonomous relay system. Efforts during the feasibility phase resulted in an API standard known as the Reasoner Standard API. Like current knowledge providers (see the list of Translator knowledge providers at smart-api.info for examples), awardees should expect that their services will be invoked by other Translator tools, such as autonomous relay agents, at all stages of the program. The FOA states that Knowledge Providers will be domain-specific and that Autonomous Relay Agents will need to traverse this federated system of Knowledge Providers. Is this a requirement of Autonomous Relay Agents? Or, is this an example only? Would a large knowledge graph that an Autonomous Relay Agent queries be an acceptable application? Autonomous Relay Agents are tools used to determine which Knowledge Providers to invoke when a query is made of the system, identify the most relevant and robust information from their responses and help to guide further iterations within the Autonomous Relay System. Autonomous Relay Agents will generate, retrieve and synthesize knowledge provided from Knowledge Providers by employing novel analytic approaches that enable Translator to address challenging translational research questions. Applicants should address each of the program component objectives. In addition to reviewing the component objectives, using the component evaluation criteria also may provide more clarity. NCATS strongly encourages all applicants to closely review the component and shared evaluation criteria. Are there technical requirements on Knowledge Providers and Autonomous Relay Agents, in terms of interfaces that must be implemented or technologies that must be used? Alternatively, will all requirements be determined by the Standards and Reference Implementation component? Awardees should utilize current Translator standards (https://github.com/NCATS-Tangerine/kgx). Awardees of all components will aid in the planning and implementation of data and software standards for Translator. The standards will apply to all components of the Translator architecture including the reference and production implementations. Some applicants may be having difficulty deciding which component is the best fit for their group. What guidance can NCATS provide for making this decision? In addition to reviewing the component descriptions, using the component evaluation criteria also may provide more clarity. NCATS strongly encourages all applicants to closely review the evaluation criteria to determine which component would be the best fit. The FOA lists several objectives for each program component. Is an application for a given component required to address every stated objective? Applicants should address each of the program component objectives. In addition to reviewing the component objectives, using the component evaluation criteria also may provide more clarity. NCATS strongly encourages all applicants to closely review the component and shared evaluation criteria. Will different data types that only pertain to cancer but are not applicable to other diseases be admissible? At this stage in the program, disease-specific data types would be a lower priority. How will existing user interfaces (UIs) be included in the program? While the development of the central Translator UI is out of scope for this FOA, interfaces required to support user interaction to catalog compelling use-cases may be used. However the results that are returned through these interfaces will need to be compliant with the current Translator standards. Does NCATS expect a page on Previous Work Examples only for Applicants for the Translator Standards and Reference Implementation component? Yes. Applicants for the Translator Standards and Reference Implementation component only should include a detailed description of prior open-source, enterprise software developed by members of the proposed project team, including links to current versions of such software, as well as previous examples of developing and implementing software and/or data standards (e.g., participation in ISO or W3C standards) that is no more than two pages Components - Knowledge Providers If there is a knowledge type that currently does not exist from the Translator feasibility stage, how do we best integrate the new knowledge type? As an exploratory component? Knowledge Providers will seek out, integrate and provide high-value AI-ready data sources within a specific scope of knowledge relevant to Translator. Knowledge Providers are encouraged to integrate knowledge from the same or closely related domains to enable new insights. Should applicants with data from multiple scientific domains submit separate applications for each knowledge provider? Not necessarily. Applicants who intend to use a common platform to onboard and integrate data from multiple domains may submit a single application. Is there an expectation that a funded knowledge provider will create an application program interface (API) to allow other services access? Is that expected to happen during the first segment of the project? Efforts during the feasibility phase resulted in an API standard known as the Reasoner Standard API. Like current knowledge providers (see the list of Translator knowledge providers at smart-api.info for examples), awardees should expect that their services will be invoked by other Translator tools, such as autonomous relay agents, at all stages of the program. Can a knowledge provider application focus on scalable technologies and approaches or should knowledge providers focus on a specific domain? The focus should be on a domain. Applicants who intend to use a common platform that could be used to onboard and integrate data from multiple domains would be allowed. Components - Autonomous Relay Agents With respect to the scale and scope of Autonomous Relay Agents, will the Autonomous Relay System call an individual Autonomous Relay Agent and expect that Autonomous Relay Agent to perform end-to-end question answering? Or, is it acceptable to restrict the scope of individual Autonomous Relay Agents (e.g., enrichment of a gene list or filtering knowledge graphs by select criteria)? Knowledge Providers accommodate a variety of analytical approaches (including extrapolation, expansion, filtering and machine learning) to support the exploration of knowledge and generation and hypotheses. Autonomous Relay Agents are developing strategies that can be applied more generally/broadly to integrate knowledge from many different domains for distilling relevant information from multiple providers and articulating the impact of the proposed approach to the overall success of returning relevant, quality responses to the Autonomous Relay System. The Autonomous Relay System will iterate across Autonomous Relay Agents to return the most relevant and highest quality potential responses. Are Autonomous Relay Agents defined by the interface that they implement, by some definition of their function, or simply by the idea that they will plug into an as-yet-undefined larger system (i.e., the Autonomous Relay System)? Autonomous Relay Agents are developing strategies that can be applied more generally/broadly to integrate knowledge from many different domains for distilling relevant information from multiple providers and articulating the impact of the proposed approach to the overall success of returning relevant, quality responses to the Autonomous Relay System. Autonomous Relay Agents may call multiple knowledge providers. The Autonomous Relay System will iterate across Autonomous Relay Agents to return the most relevant and highest quality potential responses. Is there a role for User Interfaces in the Autonomous Relay Agents components, either to pose queries, interpret results or collect user input mid-query? Or, will the User Interface be strictly within the domain of the Autonomous Relay System? Development of the Translator user interface is not included in the scope of the FOA. Are autonomous relay agents expected to work with any knowledge provider? While the Knowledge Providers will support depth of knowledge within a limited scope of biology, the autonomous relay agents should adroitly handle the integration of knowledge from multiple Knowledge Providers and thus multiple different domains of biomedical knowledge. Is it possible that interactive Autonomous Relay Agent components intended for use by system developers to achieve specific software-development objectives (e.g., quality assurance), but not intended to be "the Translator user interface", are in scope for an Autonomous Relay Agent component application? The goal is to have an agent that is autonomous. We will not support the development of a user interface and expect awardees to use existing tools and derivative reports to achieve specific software-development objectives (e.g., quality assurance) and metrics. Components - Standards and Reference Implementation Presumably, the Standards and Reference Implementation component is intended to function largely as a governance body, a technical research and development body, or an implementation body. However, is there a particular emphasis? If the Standards and Reference Implementation component is primarily governance related, what sort of prototype would be appropriate? The Standards and Reference Implementation component will further the program through a collaborative determination of standards and implementation of a reference system. Applicants should address each of the program component objectives. In addition to reviewing the component objectives, using the component evaluation criteria also may provide more clarity. NCATS strongly encourage all applicants to closely review the component and shared evaluation criteria. It's hard to imagine a prototype for the Standards and Reference Implementation component. Can NCATS provide guidance? The prototype for the Standards and Reference Implementation component should complement the written application, including the transition from prototype presented to production implementation, given that other consortium members will provide input after awards are made. | Questions and Answers About OTA-19-009 | Questions and Answers About OTA-19-009 |
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