DAta | National Center for Advancing Translational Sciences

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12988	NCATS-Supported Research Shows Potential for Altering Body Fat	Brown fat is tissue in the body that can burn large amounts of energy and generate heat. Scientists have been studying brown fat to treat obesity, but they have not found a practical, safe way to increase this fat or to make it from white fat, which stores energy. After seven days of the new browning process, human white fat tissue looks like brown fat. (Brian M. Gillette/Columbia University Photo) That is, until now: Researchers at Columbia University have discovered a new way to take white fat from a mouse, turn it into brown fat and return it to the mouse. Nicole Blumenfeld, lead author on the 2018 study, is a biomedical engineering Ph.D. student and a Precision Medicine Predoctoral Fellow supported by NCATS’ Clinical and Translational Science Awards Program hub at Columbia University. The new fat conversion process starts with removing some white fat and placing it in a liquid containing six different compounds. After three weeks, the tissue had the properties of brown fat. The team returned this newly brown fat to the mice, and eight weeks later, the tissue seemed to be working normally. The team also tried the process on human white fat tissue, which turned into what appeared to be brown fat. Although obese mice with converted brown fat did not lose more weight than mice who were not given more brown fat, the researchers hope future work will improve the process and lead to weight loss. This progress could set the stage for testing in humans and potentially a much-needed new treatment approach for obesity. Read more about this advance from Columbia University. Posted November 2018	CTSA Program-supported researchers at Columbia University have discovered a new way to take white fat from a mouse, turn it into brown fat and return it to the mouse.	/sites/default/files/columbia_brown_fat_1260x630.jpg	Research Shows Potential for Altering Body Fat	CTSA Program-supported researchers at Columbia University have discovered a new way to take white fat from a mouse, turn it into brown fat and return it to the mouse.	/sites/default/files/columbia_brown_fat_1260x630.jpg	Research Shows Potential for Altering Body Fat
13180	Rules for Participating in the Challenge	Innovators must be 18 years of age or older and may participate singly or as part of one or more teams. Teams are not limited in the number of members. Each team must designate a captain who must be a U.S. citizen or permanent resident who is responsible for all correspondence regarding this Challenge. Teams may also merge, collaborate, subdivide or otherwise organize themselves and their members as needed to prepare a solution for this Challenge. To be eligible to win a prize under this Challenge, an individual or entity: Shall have registered to participate in the Challenge under the rules promulgated by NIH as published in this notice; Shall have complied with all the requirements set forth in this notice; In the case of a private entity, shall be incorporated in and maintain a primary place of business in the United States, and in the case of an individual, whether participating singly or in a group, shall be a citizen or permanent resident of the United States. However, non-U.S. citizens and non-permanent residents can participate as a member of a team that otherwise satisfies the eligibility criteria. Non-U.S. citizens and non-permanent residents are not eligible to win a monetary prize (in whole or in part). Their participation as part of a winning team, if applicable, may be recognized when the results are announced. May not be a federal entity or federal employee acting within the scope of their employment; May not be an employee of HHS (or any component of HHS) acting in their personal capacity; Is employed by a federal agency or entity other than HHS (or any component of HHS), should consult with an agency ethics official to determine whether the federal ethics rules will limit or prohibit the acceptance of a prize under this Challenge; May not be a judge of the Challenge or any other party involved with the design, production, execution or distribution of the Challenge or the immediate family of such a party (i.e., spouse, parent, stepparent, child, or stepchild). Federal grantees may not use federal funds to develop their Challenge submissions unless use of such funds is consistent with the purpose of their grant award and specifically requested to do so due to the Challenge design and as announced on Challenge.gov. Federal contractors may not use federal funds from a contract to develop their submissions or to fund efforts in support of their submissions. Submissions must not infringe upon any copyright or any other rights of any third party. By participating in this Challenge, each individual (whether competing singly or in a group) and entity agrees to assume any and all risks and waive claims against the federal government and its related entities (as defined in the COMPETES Act), except in the case of willful misconduct, for any injury, death, damage or loss of property, revenue or profits, whether direct, indirect or consequential, arising from participation in this Challenge, whether the injury, death, damage or loss arises through negligence or otherwise. Based on the subject matter of the Challenge, the type of work that it will possibly require and an analysis of the likelihood of any claims for death, bodily injury, property damage or loss potentially resulting from Challenge participation, no individual (whether competing singly or in a group) or entity participating in the Challenge is required to obtain liability insurance or demonstrate financial responsibility in order to participate in this Challenge. By participating in this Challenge, each individual (whether competing singly or in a group) and entity agrees to indemnify the federal government against third-party claims for damages arising from or related to Challenge activities. An individual or entity shall not be deemed ineligible because the individual or entity used federal facilities or consulted with federal employees during the Challenge if the facilities and employees are made available to all individuals and entities participating in the Challenge on an equitable basis. By participating in this Challenge, each individual (whether participating singly or in a group) and each entity grants to NIH an irrevocable, paid-up, royalty-free nonexclusive worldwide license to reproduce, publish, post, link to, share and display publicly the submission on the web or elsewhere. Each innovator will retain all other intellectual property rights in their submissions, as applicable. NIH reserves the right, in its sole discretion, to (a) cancel, suspend or modify the Challenge and/or (b) not award any prizes if no entries are deemed worthy. Each individual (whether participating singly or in a group) or entity agrees to follow all applicable federal, state and local laws, regulations and policies. By participating in this Challenge, each individual (whether participating singly or in a group) warrants that he or she is the sole author or owner of or has the right to use any copyrightable works that the submission comprises, that the works are wholly original with the innovator (or is an improved version of an existing work that the innovator has sufficient rights to use and improve) and that the submission does not infringe any copyright or any other rights of any third party of which the innovator is aware. To receive an award, innovators will not be required to transfer their intellectual property rights to NIH, but innovators must grant to the federal government a nonexclusive license to practice their solutions and use the materials that describe them. This license must grant to the United States government a nonexclusive, nontransferable, irrevocable, paid-up, royalty-free license to practice or have practiced for or on behalf of the United States throughout the world any invention made by the innovators that covers the submission. In addition, the license must grant to the federal government and others acting on its behalf a fully paid, nonexclusive, irrevocable, worldwide license in any copyrightable works that the submission comprises, including the right to reproduce, prepare derivative works, distribute copies to the public and perform publicly and display publicly said copyrightable works. To participate in the Challenge, each innovator must warrant that there are no legal obstacles to providing the above-referenced nonexclusive licenses of the innovator’s rights to the federal government. Each individual (whether participating singly or in a group) and entity participating in this Challenge must comply with all terms and conditions of these rules, and participation in this Challenge constitutes each such innovator’s full and unconditional agreement to abide by these rules. Winning is contingent upon fulfilling all requirements herein. By participating in this Challenge, each individual (whether participating singly or in a group) agrees to allow NCATS to publicly display (e.g., on websites) solution abstracts, as submitted by innovators in the submission package. By participating in this Challenge, each individual (whether participating singly or in a group) assures NCATS that any data used for the purpose of submitting an entry for this Challenge competition, were obtained legally through authorized access to such data.			Rules for Participating in the Challenge			Rules for Participating in the Challenge
12946	CTSA Program Researchers Study Telepresence Robots to Help Chronically Ill Children Attend School	Translational Science Highlight Through its CTSA Program, NCATS enabled an early-stage investigator to assemble a multidisciplinary team of technology and child development experts to evaluate and advance the emerging field of telepresence, in which virtual inclusion and engagement potentially could have an impact on child health. A four-foot-tall robot equipped with a video camera and screen rolls into a classroom on two wheels. It is remotely controlled by a child who is at home because she is too sick to attend school in person. The robot enables her to be “telepresent” and therefore a more active participant in class and with her classmates, viewing lessons, asking questions and contributing to discussions in real time. These telepresence robots are increasingly making it possible for children with chronic illnesses to attend school virtually, sometimes for the first time in their lives. The robots also help children being treated for cancer or undergoing surgery to keep up with their classmates while recovering. However, there is little information about how well the robots improve learning and keep kids socially connected or on the impact they have on the classroom. With support through the NCATS Clinical and Translational Science Awards (CTSA) Program, a multidisciplinary team of researchers in education, informatics, cognitive sciences and pediatrics at the University of California, Irvine (UCI), is advancing this emerging field. Personal Experience Drives Professional Interest School of Education Work Group C: Noah, sixth grade, uses a Double robot to study with friends. (Carol Jean Tomoguchi Photo) The lead researcher on the project, Veronica Newhart, Ph.D., knows what it is like to take long breaks from school. As a child, she missed many days of school due to congenital heart defects. She found going back to class difficult for reasons far beyond catching up on her schoolwork. “You feel isolated from your friends, and when you finally come back, it is awkward because they don’t know what to say,” said Newhart, who is supported through a postdoctoral training grant from the UCI Institute for Clinical and Translational Science (ICTS), a CTSA Program hub. “It can be a little scary when classmates go missing for long periods of time and no one talks about why.” Fast forward a bit more than a decade: Newhart was working for the Department of Public Health and Human Services in Montana. There, she saw how telemedicine enabled rural patients to talk to a doctor and receive care virtually. Newhart was interested in how similar technologies could help sick children attend school. She began a Ph.D. program in the UCI School of Education and approached her mentor about studying this approach. “He was not doing this kind of research and did not have funding for it, but he supported my idea and encouraged me to take classes and make the connections I needed for the project,” Newhart said. This led to a first-of-its-kind case study, looking at why and how children with chronic health issues, ranging from suppressed immune systems to cancer, use telepresence robots. The study suggested that one of the most important aspects of the technology was helping kids feel more connected to their friends and teachers. In one case, a child with a failing heart had been homebound for 18 months while he awaited a heart transplant. His parents attributed his exhaustion — so severe he had even stopped engaging in conversations — to his illness. But after receiving the robot, he participated through an entire first day of school virtually. He soon began talking again and had much to say about his friends, teachers and homework, leading his parents and medical team to realize his previous level of fatigue was caused by depression due to isolation. Based on cases like this, Newhart predicts that virtual inclusion and engagement could improve pediatric health by providing the motivation children often need to take their medications and follow other treatment plans. She is building on her ongoing studies and working with a pediatrician at ICTS to determine how to measure health outcomes as part of a randomized clinical trial to test her theory. Robots Present Unique Challenges Newhart cautions that attending school virtually through telepresence robots is not for everyone. One child stopped using the robot and returned to homeschooling because other kids were bullying her. Newhart hopes to understand these kinds of issues further through her research, so that parents, teachers and doctors can make informed decisions about what is best for each child. Since the technology has moved rapidly from companies to consumers without formal study, there are no guidelines or best practices. To understand what does and does not work with the technology, Newhart talks not only to the child but also to classmates and teachers who interact with the robot at school. “You can place a robot in a classroom, but if no one is talking to it or selecting it for group work, then the child is not really fully immersed in the class,” Newhart said. “We need to study whether other children and teachers see and accept the robot as a traditional student and if the student participating by robot feels a sense of belonging in the classroom.” A New Interdisciplinary Field Finds a Home One of challenges in studying this emerging field, according to Newhart, is figuring out where her research fits more broadly. While completing her graduate work and looking to continue and expand it as a postdoctoral student, she realized it did not fit neatly into a specific area, which made it difficult to find the right job. But ICTS was a natural fit because she had connections through both the CTSA Program and the university. The postdoctoral TL1 training grant helped her continue and expand her case studies and assemble a team of experts, including her primary mentor for her postdoctoral training, Jacquelynne Eccles, Ph.D., a psychologist in the UCI School of Education. Veronica Newhart sits near a robot used for students to attend school. (Steve Zvlius/ University of California, Irvine Photo) “Veronica is at the cutting edge of linking educational issues into pediatrics,” Eccles said. “And through mentoring Veronica, I am now plugged into the CTSA Program, which is fantastic. It’s opened up a great opportunity to work with people in a clinical setting, which I would not have done otherwise.” Newhart’s secondary mentor is a social roboticist who will help determine which aspects of the robot can enable the child to make the best use of the technology and have the best outcomes. With the help of her mentors and collaborators, Newhart is building a national database of the services homebound children receive and use; no such database currently exists, and there is no consistency in the services children receive. She hopes the database will spur faster progress in this emerging field. Newhart also thinks the use of these robots to attend school virtually might have far-reaching implications for society. “Historically, these children couldn’t attend school, so serious illness was easier to ignore. I am really interested to see how society’s views on health may change if illness doesn’t disappear from the classroom. I am excited to see where this field goes.” Posted November 2018	CTSA Program researchers study and evaluate the use of robots in the classroom to help chronically ill children attend school.	/sites/default/files/robotics-ucirvine1_1260x630.jpg	Robots Help Ill Kids Attend School	CTSA Program researchers study and evaluate the use of robots in the classroom to help chronically ill children attend school.	/sites/default/files/robotics-ucirvine1_1260x630.jpg	Robots Help Ill Kids Attend School
12937	2018 CCIA Administrative Supplements Projects	CTSA Program External Reviewer Exchange Consortium Dissemination of an Online and Interactive Individualized Development Plan Tool to Advance Clinical and Translational Science Career Development Implementation Science Curriculum to Accelerate Translation in the CTSA Program Increasing Recruitment and Retention in Research through Participant Engagement at Fixed and Mobile Blood Donation Centers Online Learning Resources for Team Science and Community Engagement Social Networks to Map Team Science Using Barbershops to Engage Black Men in Research Across the CTSA Program CTSA Program External Reviewer Exchange Consortium University of California, Irvine Principal Investigator: Dan Cooper, M.D. Contact: icts@uci.edu Website: http://www.icts.uci.edu/national/cerec.php The CTSA Program External Reviewer Exchange Consortium (CEREC) is a collaborative effort among nine CTSA Program hubs (UC Irvine, The Ohio State University, University of Arkansas for Medical Sciences, Virginia Commonwealth University, Medical College of Wisconsin, University of Alabama at Birmingham, University of Washington, University of Southern California, and Harvard University) to exchange reviews of pilot project applications using qualified subject matter expert reviewers and removing conflicts of interest with pilots. CEREC will: Coordinate the review of each of the nine institutions’ pilot grant applications by qualified, unaffiliated faculty reviewers; Use a web-based portal (CEREC Central) that can be accessed by each CTSA Program partner hub to view proposals in real-time; Optimize the quality of scientific review for pilot projects; and Evaluate the efficiency of the CEREC peer-review exchange process model. This multi-CTSA Program hub peer-review exchange process model has the potential to be duplicated and disseminated throughout other CTSA Program networks to accommodate and enrich rigorous reviews of pilot projects funded through the CTSA Program. Dissemination of an Online and Interactive Individualized Development Plan Tool to Advance Clinical and Translational Science Career Development University of Pittsburgh UL1 Principal Investigator: Steven Reis, M.D. Contact Principal Investigator: Doris Rubio, Ph.D. The University of Pittsburgh, in partnership with Indiana University, University of Southern California and University of Pennsylvania, proposes enhancing and disseminating the University of Pennsylvania’s online and interactive tool to assist clinical and translational trainees to plan and discuss their career development goals with their mentoring teams. This Individual Development Plan (IDP) tool will: Track goal setting, deadlines, commitments and productivity through dashboard metrics; Maximize the user experience with interactive interfaces; Give trainees the opportunity to interact with and obtain real-time and continuous feedback from multiple mentors over time on CTSA-identified clinical and translational research competencies; and Monitor KL2 scholars and TL1 trainees continuously along the different stages of research training programs. This project will provide an effective tool to develop and manage an IDP that can be adopted at any institution’s internal trainee portal. The dissemination of this tool across the CTSA Program is expected to improve mentors’ interactions with their trainees or scholars and to facilitate the storing and tracking of career and clinical and translational research competency metrics. Implementation Science Curriculum to Accelerate Translation in the CTSA Program University of California, Los Angeles Principal Investigator: Steven Dubinett, M.D. The science of implementation and dissemination is an emerging, multidisciplinary field that aims to improve the relevance and uptake of research-based knowledge in real-world settings. This project proposes to disseminate curricular and course content and expertise in implementation science among six CTSA Program hubs — University of California (UC) Davis, UC Irvine, UC San Diego, UC San Francisco, and University of Southern California — with the goal of enhancing CTSA Program capacity in implementation science. The overarching aims are to: Increase the capability of CTSA Program hubs to train implementation science investigators; Develop a model for preparing health systems and public health agencies to apply implementation science methods; and Disseminate best practices in implementing enhanced, collaborative training in a multi-institutional CTSA Program network through publications, presentations, and sharing models and curricula. This project will support CTSA Program hubs in preparing researchers to develop effective interventions in “real-world” settings and to increase the readiness of leaders and key staff in local health systems and public health agencies to use these methods. Ultimately, this project will demonstrate how CTSA Program hubs can share expertise so that researchers and health care leaders have more success solving care delivery challenges that affect patients and populations. Increasing Recruitment and Retention in Research through Participant Engagement at Fixed and Mobile Blood Donation Centers University of California, San Diego Principal Investigator: Gary S. Firestein, M.D. The University of California, San Diego (UCSD), Medical College of Wisconsin and Stanford University hubs will partner to implement the use of both fixed and mobile blood donation centers as innovative sites to engage a greater number of participants in research projects and clinical trials. This approach to recruitment has been demonstrated to be effective at UCSD and is now being expanded to two additional hubs to reach potential participants who would not normally participate in research or clinical trials. This supplement will support: Partnerships between CTSA Program hubs and blood banks to implement fixed blood donation centers as clinical research sites; Expansion of the geographic reach of research projects or clinical trials to rural areas, immobile populations and places of business by utilizing mobile blood donation units as “mobile clinical trial centers” during regular and off hours; and Measurement of the impact on acceleration of translational research achieved from utilizing blood donation centers as satellite clinical research sites. The inability to recruit and retain the required participants in a research project or a clinical trial is a major bottleneck for translational science. This project has the potential to demonstrate the impact of an innovative way to encourage hard-to-reach and underserved communities to participate in research projects and clinical trials. Online Learning Resources for Team Science and Community Engagement Northwestern University Principal Investigator: Donald Lloyd-Jones, M.D., Sc.M. Website: https://www.teamscience.net/ Teamscience.net is the first comprehensive online, open-source learning tool about team science. Users can navigate through four learning modules that provide an introduction to team science and can participate in simulated challenges in behavioral, clinical and basic science teams. However, it has become increasingly clear that the software platform on which teamscience.net operates is outdated and that content needs a significant upgrade. Northwestern University, along with the University of Illinois at Chicago, will: Upgrade, expand, evaluate and disseminate the team science learning resource; Improve the user experience by converting the format from Flash to HTML5; and Build a new module in collaboration with local experts to address the needs of teams in community-engaged research. To enhance dissemination, a Shareable Content Object Reference Model-compliant learning management system (LMS) will be used. This project will allow other CTSA Program hubs to import the learning tool onto their own LMSs. This collaboration will lead to the dissemination of the enhanced team science e-learning resource across CTSA Program hubs and prepare the resource to be sustainable for the future. Social Networks to Map Team Science University of Florida Principal Investigator: David R. Nelson, M.D. The University of Florida and the University of Kentucky CTSA Program hubs will employ social network analysis to understand the pattern and determinants of scientific collaboration within and around CTSA Program hubs. Although CTSA Program hubs are increasingly encouraged to promote team science and collaborations within and between hubs, there is little consensus on what data and methods should be used to measure and evaluate the contribution of different CTSA Program hubs to team science in their respective academic institutions. This project will provide support for the University of Florida to disseminate their approach of social network analysis to the University of Kentucky to develop metrics and methods that can be used to inform the establishment of cross-hub collaborations. This collaborative effort will: Describe the scientific and collaborative profile of CTSA Program hubs as networks of research communities; Assess the impact of CTSA Program programmatic efforts on team formation; and Evaluate the effect of CTSA Program-induced collaborations on research productivity at both the team and individual levels. Network science methods will be used to identify cohesive research communities or clusters in the networks. This project has the potential to disseminate a blueprint for consistent monitoring and evaluation of impact of the CTSA Program on scientific collaborations and team science. Using Barbershops to Engage Black Men in Research Across the CTSA Program University of California, Los Angeles Principal Investigator: Steven M. Dubinett, M.D. This project will disseminate a novel intervention, from the University of California, Los Angeles (UCLA) hub to the Vanderbilt University Medical Center CTSA Program hubs, in which pharmacists partner with barbershops to test black patrons for high blood pressure, prescribe high blood pressure medications as appropriate, and follow up with participants at future haircut appointments to check that the medications are working and not causing problems (see story here). The project will: Identify a core group of stakeholders in the Vanderbilt CTSA Program hub and the Nashville community to build a network of barbershops to engage in health promotion and health research among black men; Establish an initial network of eight barbershop research sites in Nashville; Use the new Nashville barbershop network to execute a smaller version of the Los Angeles Barbershop Blood Pressure Study; and Develop a complete manual of operating procedures and training materials for all roles of clinical study (lead barber, clinical pharmacist, community physician champion, etc.). This project has the potential to demonstrate the impact of directly engaging communities and utilizing alternative health care delivery, through pharmacists, in nontraditional settings. This collaborative project, focusing on a novel community engagement approach, has the potential to be disseminated across the CTSA Program to include other underrepresented communities.			2018 CCIA Administrative Supplements Projects			2018 CCIA Administrative Supplements Projects
12940	2017 CCIA Administrative Supplements Projects	Developing Policies and Practices to Leverage Data Innovation to Promote Study Recruitment Enhancing CTSA Capacity Through Multi-Institutional Data Warehousing I-CorpsTM at NCATS Program Innovation Labs to Enhance CTSA Program Network Capacity Innovative Video Consenting for Precision Medicine Multi-CTSA Mini-Sabbatical Evaluation and Quality ImprovemeNt (SEQUIN) N-Lighten Network: A Federated Platform for Education Resource Sharing Regulatory Guidance for Academic Research of Drugs and Devices (ReGARDD) SPARCRequest©: An e-commerce Solution for Multisite Research and Clinical Trials Trial Finder Developing Policies and Practices to Leverage Data Innovation to Promote Study Recruitment Yale University Principal Investigator: Robert S. Sherwin, M.D. Contact: Tesheia Johnson Yale proposes to collaborate with the Rockefeller and Washington University CTSA Program hubs to disseminate an approach that Yale has implemented to enhance its recruitment to clinical trials through institutional change. The goal is for the three hubs to exchange scientific information regarding the implementation of: systems and models for patients to opt in or opt out of their data being used for recruitment to clinical trials and for clinical research, electronic IRB management systems, grants management platforms, and clinical research or trial management systems. The project will leverage both the research management strengths of each partnering hub and the institutional investments in technology platforms, educational resources and development of best practice standards at each institution. The exchange will focus on processes for expanding the participation in clinical and translational research by leveraging electronic health records and other technology, along with a translation and dissemination strategy that is likely to be transferable across the CTSA Program. A national framework could emerge that would aid each CTSA Program hub in applying modern informatics and common best practices to accelerate participant recruitment to clinical trials. Enhancing CTSA Capacity Through Multi-Institutional Data Warehousing University of California, Los Angeles Principal Investigator: Steven M. Dubinett, M.D. Contact: Doug Bell Modern scientific discoveries require larger populations of data, which are seldom available to individual institutions. Unfortunately, provisioning research data from federated systems requires data extraction from separate patient data warehouses at each institution, and the resulting data often are poorly normalized, with substantial data missing and with additional data on patients who are not actually comparable. This CTSA Program administrative supplement will fund the evaluation of the potential utility of the Big Healthcare Data Initiative for providing high-quality research data sets, with a particular focus on data that could simultaneously inform performance improvement and clinical science. Specifically, with the aid of this supplement, the project investigators will: Implement a data research prioritization process as a component of the governance process being established for a multi-institutional centralized data warehouse; Assess the results of provisioning data to address high-priority research questions from a multi-institutional centralized data warehouse in comparison with data extracted from single institution data warehouses, in terms of (a) completeness and accuracy, and (b) efficiency of effort; Implement corrections in data harmonization and data processing to address challenges identified from assessments of research data obtained from the centralized warehouse; and Disseminate lessons learned in implementing research data provisioning from a multi-institutional centralized clinical data warehouse through publications, presentations and open-source code sharing. The proposed supplement is in line with the CTSA Program mission, as it will enable investigators to evaluate the utility of a unified data warehouse for providing high-quality research data sets, disseminate lessons learned to the entire CTSA Program network and lay the foundation for more impactful, multi-CTSA Program hub research. The results of the proposed project will serve to guide data warehousing and data provisioning activities among the nation’s CTSA Program institutions, forming a foundation for more impactful translational research spanning multiple CTSA Program institutions. I-Corps at NCATS Program University of Alabama at Birmingham Principal Investigator: Robert P. Kimberly, M.D. Contact: Molly Wasko, Ph.D. Website: https://www.uab.edu/ccts/training-academy/innovation/i-corps This project is a collaborative effort among nine CTSA Program hubs: University of Alabama at Birmingham, Georgia Institute of Technology (part of the Emory University hub), Pennsylvania State University, Rockefeller University, University of California, Davis, University of Colorado Denver, University of Miami, University of Massachusetts, and University of Michigan. University of Alabama at Birmingham researchers aim to adapt and disseminate the existing National Science Foundation (NSF) Innovation Corps (I-CorpsTM) and I-CorpsTM at NIH programs to meet the needs of researchers and clinicians at academic medical centers. The overarching aims are: Develop a uniform, four-week curriculum that will be considered part of the official I-CorpsTM body of knowledge, specific to the commercialization of clinical and translational research discoveries; Build capacity locally and regionally across CTSA Program hubs through a regional Train-the-Trainer program; and Establish common metrics and an evaluation framework to assess the effectiveness and impact of the I-CorpsTM at NIH program across CTSA Program institutions. Like the NSF and NIH I-CorpsTM programs, this project prepares scientists and engineers to extend their focus beyond the university laboratory and accelerates the economic societal benefits of select basic research projects that are ready to move toward commercialization. Innovation Labs to Enhance CTSA Program Network Capacity University at Buffalo, State University of New York Principal Investigator: Timothy F. Murphy, M.D. Contacts: Timothy F. Murphy, M.D., and Larry Hawk, Ph.D. Website: http://www.buffalo.edu/innovationlabs.html An Innovation Lab is a promising and revolutionary means for constructing new interdisciplinary teams and stimulating novel research solutions across the CTSA Program consortium. Participants — along with a director, organizers, subject matter guides and Knowinnovation facilitators — communally explore a problem in space, generate a broad range of ideas and form transdisciplinary teams to pursue research projects. The Innovation Lab targets early-stage investigators who have limited networks and opportunities for collaboration and during an opportune time in their careers when this experience may launch their independent — yet interdisciplinary and collaborative — research programs. The project is a collaboration between the University at Buffalo and Vanderbilt University Medical Center CTSA Program hubs and the Knowinnovation facilitation team. The team will achieve the following specific aims: With ongoing input from multiple stakeholders (NCATS, CTSA Program hubs and Domain Task Forces) the team will develop, run and track the impact of two pilot Translational Workforce Development Innovation Labs (one at University at Buffalo and one at Vanderbilt University), and Evaluate the impact of the Innovation Labs in a randomized controlled that randomly assigns matched applicants to an Innovation Lab or a “treatment as usual” control group. At the conclusion of this project, the investigators will have demonstrated the effectiveness of an innovative approach to developing new and interdisciplinary teams of young investigators that are prepared to tackle challenges in translational science. Innovative Video Consenting for Precision Medicine University of California, Los Angeles Principal Investigator: Steven M. Dubinett, M.D. Contact: Arash Anaeim Revolutions in genomic and information technologies have created unprecedented opportunities to advance the diagnosis and treatment of disease across the entire spectrum of medicine. However, to fully accomplish these goals, it is essential to collect genomic and clinical data from a very large and diverse patient population in an ethical, informed manner without disrupting the clinical flow for patients, staff and providers in high-volume centers. This CTSA Program administrative supplement will strengthen collaboration among five CTSA Program hubs (US BRAID: University of California, Davis; University of California, Irvine; University of California, Los Angeles; University of California, San Diego; and University of California, San Francisco) for developing and applying novel approaches to informed consent, including the use of remote (telemedicine) consenting, in order to enable a diverse population of patients to have access to research participation. Specifically, with the aid of this supplement, the project will: Develop and pilot a revised video/electronic consenting approach; Validate and pilot test a tiered consenting process; Create 20 personalized video vignettes in support of biobanking consent; and Create a Community Advisory Board to enhance community outreach. This collaborative effort to enhance informed consent and foster recruitment is in line with CTSA Program goals of enhancing research methods and fostering communication among CTSA Program hubs to make clinical and translational trials more efficient. The project investigators will develop a novel consenting tool, determine best practices across five CTSA Program hubs, and ensure that the resulting developments are scalable across the entire network and beyond. Multi-CTSA Mini-Sabbatical Evaluation and Quality ImprovemeNt (SEQUIN) University of Alabama at Birmingham Principal Investigator: Robert P. Kimberly, M.D. Contact: Kenneth Saag, M.D. Website: https://clic-ctsa.org/opportunities_board/sequin This supplement will support the dissemination of mini-sabbaticals for KL2 scholars and TL1 trainees designed to enrich career development through experiences complementary to those offered at an investigator’s home institution. The CTSA Program hubs at the University of Alabama Birmingham, New York University and the University of Massachusetts have developed this program among their hubs and are now poised to disseminate this program across the entire CTSA Program through a collaboration with the CTSA Program Coordinating Center, based out of the University of Rochester. Specifically, this supplement will: Conduct a national formative evaluation of mini-sabbatical experiences at CTSA Program hubs; Use feedback from the evaluation to refine the initial preliminary report on mini-sabbatical “best practices” developed, based on experiences at the three CTSA Program hubs; and Build from existing offerings at the three CTSA Program hubs to catalog a national mini-sabbatical to connect CTSA Program scholars and trainees with optimal mini-sabbatical opportunities. The goal of these mini-sabbaticals is to acquire added competencies in specific areas of translational research, with the experience tailored to meet each investigator’s individual training needs. N-Lighten Network: A Federated Platform for Education Resource Sharing Ohio State University Principal Investigator: Rebecca D. Jackson, M.D. Contact: Rebecca D. Jackson, M.D. Researchers at Harvard University, Oregon Health & Science University and The Ohio State University CTSA Program hubs will develop educational resources, tools and technologies and make them available online to trainees, investigators and other members of the translational scientific team. Specifically, with the aid of this supplement, the project strives to: Undertake development and proof-of-concept experiments to create the foundation for a CTSA Program-wide federated education resource entitled the N-Lighten Network; Identify strategies that create value for CTSA Program hubs, educators and trainees to enhance utilization and engagement of N-Lighten for clinical and translational investigator education and career development; and Develop and pilot methodologies to evaluate educational resources based upon use and feedback from diverse trainees across the clinical and translational science spectrum from the two CTSA Program hubs and by clinical and translational science educators drawn from the Workforce Development Domain Taskforce and interested CTSA Program hubs. At its conclusion, the project will have demonstrated both the feasibility and value of a semantically indexed, federated platform of educational resources, providing the foundation of a CTSA Program-wide N-Lighten Network that can be applied to facilitate and complement the education and training of all members of the clinical and translational workforce. Regulatory Guidance for Academic Research of Drugs and Devices (ReGARDD) University of North Carolina at Chapel Hill Principal Investigator: John B. Buse, M.D., Ph.D. Contact: John B. Buse, M.D., Ph.D. Website: http://www.regardd.org/ While recent medical advances demand new regulatory guidance, few institutions have the breadth of expertise needed to address the unique issues arising from the expanding field of translational science. To that end, representatives of Duke University, the University of North Carolina at Chapel Hill and Wake Forest University CTSA Program hubs will expand an innovative platform, Regulatory Guidance for Academic Research of Drugs and Devices (ReGARDD). The platform is designed to share expertise and methodologies across institutions to provide researchers with the tools and resources necessary to find successful pathways from discovery to clinical implementation of new and innovative drugs, biologics, medical devices and therapies. Specifically, this supplement will enhance the collaborative ReGARDD program by: Expanding the content of the shared regulatory website to include educational resources that meet and support academic investigators’ regulatory needs; Developing the capabilities of the regional regulatory forum to assist academic researchers in navigating an increasingly complex regulatory environment; and Disseminating to the CTSA Program network an innovative approach to provide regulatory guidance, share expertise and address regulatory barriers to academic investigators involved in clinical and preclinical research. Combining the regulatory insight of three North Carolina CTSA Program hubs to share successful strategies and lessons learned could lead to the establishment of a robust, regional outreach program that would facilitate meaningful and fruitful collaborations among multiple stakeholders. SPARCRequest: An e-Commerce Solution for Multisite Research and Clinical Trials Medical University of South Carolina Principal Investigator: Kathleen T. Brady, M.D., Ph.D. Contacts: Leslie Lenert and Royce Sampson Websites: https://research.musc.edu/resources/sctr/research-resources/tools/sparcrequest MUSC SPARCRequest: https://sparc.musc.edu/ Videos: SPARCRequest Introduction: https://www.youtube.com/watch?time_continue=6&v=Yq7TcdzqAlA Using SPARCRequest: https://youtu.be/3sFdLhBlchYSPARCRequest Wiki: https://sparcrequest.atlassian.net/wiki/spaces/RD/overview Researchers at the Medical University of South Carolina will adapt, test, and deploy strategies derived from e-commerce solutions to promote greater collaboration and accelerate the conduct of multisite research and clinical trials within the CTSA Program network — particularly with the launch of the CTSA Program Trial Innovation Network. The electronic storefront program, called SPARCRequest©, aims to support inter-institutional ordering and budgeting of services and resources, as well as tracking of service fulfillment and invoicing. The Medical University of South Carolina CTSA Program hub, in collaboration with the University of Utah and the University of Iowa hubs, will achieve the following overarching aims: Develop a governance model to provide a structure for sustainability, decision-making and co-development across CTSA Program hub adopters and other stakeholders for open-source SPARCRequest©; Develop, implement, assess and disseminate open-source software that fosters adoption by other institutions, including continuous process improvement and collaborative project management; and Support the CTSA Program Trial Innovation Network to optimize efficiency by providing a platform for remote sharing of research resources and rapid multisite budget development. The goal of the project is to enhance multisite study conduct and realize systematic efficiencies through a collaboratively owned and cooperatively managed electronic marketplace for CTSA Program hubs to order, price and fulfill services and study assessments across the CTSA Program network. Trial Finder University of California, San Francisco Principal Investigator: Harold Collard, M.D. Contact: Harold Collard Website: https://clinicaltrials.ucbraid.org/ Failure to recruit adequate numbers of eligible and diverse participants, combined with the struggle to find investigators that have specific content expertise and experience, often results in lengthy delays and higher costs associated with clinical trials. To address these challenges, representatives of the five University of California CTSA Program hubs aim to help patients and community members easily discover actively enrolling trials and help sponsors and researchers open studies quickly by finding local collaborators. Specifically, with the aid of this supplement, the project investigators will help develop and launch: Trial Finder, a platform enabling the public to discover all currently enrolling clinical trials across the University of California CTSA Program network and beyond; and Trialist Search, a cross-institutional search tool that facilitates the identification of expert local investigators to collaborate in multisite clinical trials. While the initial efforts will focus on the University of California, Davis; the University of California, Irvine; the University of California, Los Angeles; the University of California, San Diego; and the University of California, San Francisco CTSA Program hubs, the ultimate goal will be to expedite trial recruitment by disseminating the Trial Finder and Trialist Search approach, software, technical support, and communications strategies across the CTSA Program network and beyond.			2017 CCIA Administrative Supplements Projects			2017 CCIA Administrative Supplements Projects
12976	NCATS Day 2018: Community Engagement Resources	Returning Individual Research Results to Participants: Guidance for a New Research Paradigm An ad hoc committee reviewed the current evidence on the benefits, harms, and costs of returning individual research results, while also considering the ethical, social, operational, and regulatory aspects of the practice. The resulting report offers a process-oriented approach to returning individual research results that considers the value to the participant, the risks and feasibility of return, and the quality of the research laboratory. Institute of Medicine (IOM) Recommendations for Returning Individual Research Results to Participants (PDF - 65KB) This document provides a summary and outlines the 12 recommendations made by the IOM in July 2018 on returning individual research results to participants. Community Engagement Studios: A Structured Approach to Obtaining Meaningful Input from Stakeholders to Inform Research Engaging communities in research increases its relevance and may speed the translation of discoveries into improved health outcomes. Many researchers lack training to effectively engage stakeholders, whereas academic institutions lack infrastructure to support community engagement. In 2009, the Meharry-Vanderbilt Community-Engaged Research Core began testing novel approaches for community engagement, which led to the development of the Community Engagement Studio (CE Studio). This structured program facilitates project-specific input from community and patient stakeholders to enhance research design, implementation, and dissemination. Developers used a team approach to recruit and train stakeholders, prepare researchers to engage with stakeholders, and facilitate an in-person meeting with both. A tool kit was developed to replicate this model and to disseminate this approach. MRCT Center Return of Individual Results to Participants Recommendations Document (PDF - 1.8MB) This November 2017 report outlines the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard findings and recommendations on returning individual results to participants. Patient vs. Community Engagement: Emerging Issues The value proposition of including patients at each step of the research process is that patient perspectives and preferences can have a positive impact on both the science and the outcomes of comparative effectiveness research. How to accomplish engagement and the extent to which approaches to community engagement inform strategies for effective patient engagement need to be examined to address conducting and accelerating comparative effectiveness research. Participants developed and refined a framework that compares and contrasts features associated with patient and community engagement. Although patient and community engagement may share a similar approach to engagement based on trust and mutual benefit, there may be distinctive aspects that require a unique lexicon, strategies, tactics, and activities.			NCATS Day 2018: Community Engagement Resources			NCATS Day 2018: Community Engagement Resources
12868	NCATS Scientists Prioritize Compounds to Advance Research on Mitochondrial Damage	October 10, 2018Mitochondria are tiny structures inside cells that produce the energy needed to carry out a cell’s daily biological tasks. But some environmental chemicals can damage mitochondria and lead to health issues such as heart disease, diabetes, cancer, and neurodegenerative disorders.Through the Toxicology in the 21st Century (Tox21) program — a collaborative effort among NCATS, the National Toxicology Program, the Environmental Protection Agency, and the Food and Drug Administration — scientists work to improve laboratory testing methods to identify toxic chemicals and predict their toxicity in humans. A primary focus is to find new and more efficient ways to evaluate thousands of compounds that could potentially damage mitochondria.Several years ago, Tox21 scientists combed through approximately 8,300 chemical compounds, finding 622 that potentially disrupted mitochondrial activity to varying degrees. The scientists used a format called high-throughput screening, which enabled them to test thousands of compounds at once, to examine the effects of the compounds on mitochondrial function.Three chemicals (FCCP, chlorfenapyr and pinacyanol) cause damage to the cell’s mitochondria. An enzyme then facilitates the recycling of the damaged mitochondria, as shown in the top right and bottom two panels. Normal cells are shown in the upper left panel. (Environmental Health Perspectives and Nuo Sun, Ph.D., Photo)“Using animal models to evaluate thousands of compounds would be expensive, inefficient and take many years to complete,” said Menghang Xia, Ph.D., a lead in the Systems Toxicology lab for the Tox21 program at NCATS. “We would like to prioritize these compounds and choose a few compounds in the end to study in other models and eventually generate a computational model that allows us to screen them more efficiently.”In a study published in Environmental Health Perspectives, Xia and her colleagues devised such an approach. They conducted tiers of assays, or tests, to identify and prioritize compounds according to their ability to disrupt mitochondrial activity. Using this strategy, scientists narrowed the list to 34 compounds and ultimately determined that four poorly characterized chemicals should be investigated in greater detail.Most of the assays were already in use but were modified for use in NCATS’ high-throughput research facility, enabling many assays needed for this analysis to be conducted in weeks. In comparison, most animal studies take months to complete.“This is the first time a combination of tests has been developed and used to flag chemicals that can potentially disrupt mitochondrial function, and, at the same time, also help us to understand how such disruptions occurred,” said co-author Anton Simeonov, Ph.D., scientific director of the NCATS Division of Preclinical Innovation.The tests were wide-ranging. For example, the first key screening test measured the effects of compounds on mitochondrial “membrane potential,” which can indicate the impact on a cell’s ability to generate and process energy. “The mitochondrial membrane potential is one of the best ‘canary in the coal mine’ tests for chemicals that could wreak havoc on mitochondria,” Simeonov said.Study co-authors with the National Toxicology Program examined how compounds’ effects on mitochondrial function could affect the development of a commonly used laboratory model, the roundworm, while FDA collaborators showed how compounds might affect needed oxygen levels in mitochondria. Researchers also studied how compounds’ toxic effects on mitochondria affected human neuronal stem cell activity and the levels of a protein that is associated with DNA damage and many different cancers.Xia noted that a similar approach can be used as a template for other large-scale toxicity studies. In addition, the use of human cells in initial tests could help make the approach more predictive in people.The researchers hope that computational scientists will use these data to generate predictive computer models. In the meantime, Xia and her colleagues would like to test — and unravel — how such compounds might affect genes that control mitochondrial activity.	NCATS scientists collaborated with federal agencies to develop an approach that enables researchers to prioritize environmental chemicals according to their ability to disrupt mitochondrial activity.	/sites/default/files/tox21_feature_1260x630.jpg	NCATS Scientists Advance Research on Mitochondrial Damage	NCATS scientists collaborated with federal agencies to develop an approach that enables researchers to prioritize environmental chemicals according to their ability to disrupt mitochondrial activity.	/sites/default/files/tox21_feature_1260x630.jpg	NCATS Scientists Advance Research on Mitochondrial Damage
12811	CTSA Program Supports Early Development and De-Risking of Innovative Heart Valve Technology	Translational Science Highlight NCATS’ Clinical and Translational Science Awards Program support enabled the early development and “de-risking” of an innovative device that may be more durable and help patients avoid complications of heart valve replacement. The aortic valve keeps blood flowing out of the heart to the rest of the body. Calcium deposits form on the valve with age, narrowing the valve opening and disrupting blood flow. Traditionally, replacing the aortic valve meant having open-heart surgery, a risky and invasive procedure. But in 2011, the Food and Drug Administration (FDA) approved the first device for a procedure called transcatheter aortic valve replacement (TAVR). For TAVR, a cardiologist makes a small cut somewhere else in the body, such as in the groin, and threads a catheter containing the replacement valve through a large blood vessel up to the heart, where the valve is set in place. The procedure is much less invasive than traditional open-heart surgery, and patients recover more quickly. However, patients who receive TAVR may have a higher risk of complications, such as blood clots on the heart valve, than people who have the valve replaced surgically. Arash Kheradvar, M.D., Ph.D., a biomedical engineer at the University of California (UC), Irvine, has an idea about why: Squeezing the replacement valve down to a size that fits through the artery in the groin appears to damage the valve and may make it easier for blood clots to form on its surface. With support from the NCATS Clinical and Translational Science Awards (CTSA) Program hub at UC Irvine, Kheradvar began developing a device called FoldaValve that folds differently to minimize or even avoid damage to the valve. Kheradvar hopes that FoldaValve will further lower risks for patients, increase the working lifespan of the replacement valve and make TAVR available to more people. Currently, TAVR is not approved for patients at lower risk from surgery or patients younger than 65, mainly because of concerns about the durability of the valve. Understanding Valve Damage FoldaValve, a replacement heart valve with leaflets attached. (KLAB: Kheradvar Research Group Photo) A replacement valve for TAVR consists of two parts. The leaflets, which flap open and shut with each heartbeat, are affixed to a stent that sits in the opening of the aorta. For the replacement valves currently on the market, the stent is compressed, or crimped, with the leaflets inside, just before the procedure. Before crimping, the replacement valve is often more than an inch across, yet it must fit into an artery that is less than half an inch across. “If you are going to significantly crimp these valves inside the stent, what will happen to the leaflets?” Kheradvar asked. He was a bioengineering graduate student at the California Institute of Technology when TAVR was being studied as an experimental procedure in the 2000s. He was studying how blood flows through heart valves. “Everybody was super excited, but I was thinking, ‘In its current form, this invention may be costing the durability of these valves.’” In a 2014 study, Kheradvar and his colleagues showed that crimping a valve’s delicate leaflets inside the stent causes irreversible damage. Since then, other researchers have reported several cases in which calcium deposits formed on TAVR valves within about two years. Another study revealed that blood clots seem to be more likely on valves that were placed via catheter. Kheradvar suspects that the damage to the leaflets makes it easier for clots to form. These clots may lead to stroke or other health problems if not treated in time, and damage to the leaflet can shorten the lifespan of the valve and subject patients to another replacement procedure. Working from the Outside In In 2011, with support through the CTSA Program, UC Irvine awarded Kheradvar a pilot grant, which he used to develop a different TAVR technology called FoldaValve. With this approach, the leaflets are extended outside the stent for the trip from the groin to the heart. The valve is designed so that the leaflets turn inside and start working when the stent is expanded. The CTSA Program pilot funding also helped Kheradvar secure a larger grant from the Wallace H. Coulter Foundation, which enabled him to develop a delivery system for FoldaValve. So far, the valve has been implanted successfully in animals. FoldaValve solves another problem with existing valve replacement systems: The calcium deposits on the diseased aortic valves form in random places, so it can be difficult to tell where exactly the valve should be placed. “For a conventional valve, when you implant it, you’re fitting a cylinder into a bed that is not circular, due to randomly deposited calcium,” Kheradvar said. “You get gaps between your stent and that calcium, which results in leaks around the valve.” Replacement heart valves solve this problem by adding a skirt, which is very effective. In addition to having a skirt, FoldaValve is designed so that the cardiologist can reposition the valve for optimal placement to avoid leaks. If the valve is not going to work at all — or if the patient feels unwell during the procedure — it can be refolded and removed. Additionally, FoldaValve’s unique folding makes it narrower than other valves used for TAVR, which means it should be safer for patients with thin, delicate arteries. Improving Imaging FoldaValve in action (KLAB: Kheradvar Research Group Photo) Using grant support from NIH’s National Institute of Biomedical Imaging and Bioengineering, Kheradvar is also working on improving imaging during the valve replacement process. Normally, a cardiologist guides the valve using fluoroscopy, a kind of x-ray imaging that shows a continuous video of the action inside the body. In contrast, Kheradvar has mounted a tiny ultrasound probe on the catheter — something that has previously been done to position stents in the arteries that supply blood to the heart muscle. “When you see the catheter under the x-ray, it’s like you’re standing on the street and a car passes by,” Kheradvar said. “But if you have an ultrasound system on your catheter, it is like you are driving the car.” Mohammad Sarraf, M.D., a cardiologist at the University of Alabama at Birmingham, is working with Kheradvar to help further refine and test FoldaValve. Sarraf routinely performs TAVR with the two existing FDA-approved replacement valve systems, and he said that having more options on the market would be useful. “We’re learning from our patients and their complications,” he said. “It’s difficult to say that one valve system is best for all patients. Having three or four TAVR systems on the market will give us more tools to serve our patients better.” Looking Ahead Kheradvar has formed a company to further develop FoldaValve. He is currently raising private funding to move the technology forward and ensure safety and efficacy. He hopes to implement the first human trials of the valve in Europe and eventually get approval for the device from both the European Union regulatory agency and the FDA. “This project demonstrates how CTSA Program support of innovative ideas can lead to new technologies that benefit patients,” said Michael G. Kurilla, M.D., Ph.D., director of the NCATS Division of Clinical Innovation. “A small infusion of CTSA Program funding seven years ago may eventually have a big impact: a better valve replacement for patients.” “Everything starts from something,” Kheradvar said. “I’m thankful for the early CTSA Program funding, because it was crucial to securing additional funds and moving forward with the development.” Posted October 2018	CTSA Program support enabled the early development and “de-risking” of an innovative device that may help patients avoid complications of heart valve replacement.	/sites/default/files/FoldaValveSkirt_1260x630.jpg	CTSA Program Supports Early Development of Heart Valve Technology	CTSA Program support enabled the early development and “de-risking” of an innovative device that may help patients avoid complications of heart valve replacement.	/sites/default/files/FoldaValveSkirt_1260x630.jpg	CTSA Program Supports Early Development of Heart Valve Technology
13159	NCATS ASPIRE Design Challenges: Solution Submission Instructions and Template	Instructions Solution Due Dates: 12:00 p.m. ET December 31, 2018 - 12:00 p.m. ET May 31, 2019. Please use the template below to format your submission. NCATS refers to participants in the NCATS ASPIRE Design Challenges as “innovators” because all solutions will require highly innovative approaches to achieve success. Registration Process for Participants To participate in any of the NCATS ASPIRE Design Challenges, every innovator, whether an individual or member of a team, must first register. Innovators may access the registration and submission platform at Challenge.gov by searching for the following challenges: NCATS ASPIRE Design Challenge 1: Integrated Chemistry Database for Translational Innovation in Pain, Opioid Abuse Disorder and Overdose NCATS ASPIRE Design Challenge 2: Electronic Synthetic Chemistry Portal for Translational Innovation in Pain, Opioid Abuse Disorder and Overdose NCATS ASPIRE Design Challenge 3: Predictive Algorithms for Translational Innovation in Pain, Opioid Abuse Disorder and Overdose NCATS ASPIRE Design Challenge 4: Biological Assays for Translational Innovation in Pain, Opioid Abuse Disorder and Overdose NCATS ASPIRE Design Challenge 5: Integrated Solution for Translational Innovation in Pain, Opioid Use Disorder and Overdose To submit a solution on Challenge.gov, please paste the project summary into the “Description” box. Detailed solutions should be created using the word template below and must be uploaded as word documents to Challenge.gov. When submitting a solution, at the bottom of the submission page: Check the first box (“Hide the contents of my submission from all others on Challenge.gov. By checking this box, you will hide your submission and all associated files from public view. Only the agency challenge managers will see this content”). Do not check the second box (“Show associated solution files: Check this box if you have made your solution public and also want to share its associated files”). By leaving this box unchecked, project summaries will be publicly available, but only NCATS will have access to your uploaded complete solution. All innovators submitting solutions must agree to the terms & conditions. Please review the detailed rules and information and then check the “agree to terms & conditions” box while submitting a solution on Challenge.gov. Submission Requirements Solutions must: Be written in English and observe all page limits, page dimensions (8.5 x 11 inches), font size (11 point or greater), and margins (1-inch). (The template that follows meets these requirements.) Include 4 required sections Any material that exceeds stated page limits will be considered supplemental and will be used at the reviewers’ and judges’ discretion. Innovators must not use HHS’s logo or official seal or the logo of NIH or NCATS in the submissions and must not claim federal government endorsement. Please divide the submission into the 4 sections indicated in the template below. Template Section 1 Cover Page (1 page; this does not count toward the 4- and 12-page limit, for Challenges 1 - 4 and Challenge 5, respectively.) Please include the following details in the cover page: The lead innovator’s name and position in institution/organization/company List of all team members’ names and affiliations Indicate the name of the Challenge you are entering A project summary of 300 or fewer words that clearly states the advantages and novelties of the proposed solution. Note: the project summary must also be pasted into the description box at Challenge.gov. Section 2 Description of the Proposed Solution (4- and 12-page limit for Challenges 1 - 4 and Challenge 5, respectively.) Please include the following sections and content in the description of the proposed solution. Background/Significance Include background and describe any existing methods or technologies that would be used, combined or built based on the proposed design. Cite references to peer-reviewed articles that support the proposed solution (see “REFERENCES” below). Describe the tools, technologies and protocols that would be needed to develop the proposed solution. Clearly state how the proposed solution would advance discovery and development of novel treatments for pain, opioid use disorder and overdose. Innovation and Team Include an “innovation statement” that discusses the advantages and potential pitfalls of the proposed approach, and how and why combining technologies or protocols may provide advantageous results; highlight cross-discipline integration of approaches. Describe the ability of the individual or team to execute the proposed solution. If the team consists of multiple experts residing in different locations, include a brief statement to describe how the team was structured and how exchange of knowledge, ideas, and solutions was facilitated among team members. Research Design and Methods Include preliminary data, if applicable. Provide an overview of the design. Describe methods and analyses used, including any new methodology used and why it represents an improvement over the existing ones. Describe any strategy to establish feasibility and address the management of any high-risk aspects of the proposed design. Discuss the way in which the results will be collected, analyzed and interpreted. Include estimated timeframes, supporting precedents and any special resources that would be needed. List potential difficulties and limitations and how these could be overcome or mitigated If applicable, address protections of human subjects, and compliance with policies related to use of human stem cells, biosafety issues and use of technologies covered by patents or other intellectual property protection. Please review the Judging Criteria for the Challenge(s) you selected and address the criteria in your submission. Section 3 Biographical Sketches (5-page maximum; this does not count toward the 4- and 12-page limit for Challenges 1 - 4 and Challenge 5, respectively.) For each individual, whether participating solely or as a member of a team, a biographical sketch of relevant experience and expertise, including applicable publications, must be included. You may use the NIH Bibliographic Sketch format (see https://grants.nih.gov/grants/forms/biosketch.htm.) Pease provide sufficient evidence of your technical competence and describe skills and experiences that are relevant to the challenge. Section 4 References (Include only the most relevant citations; this section does not count toward the 4- and 12-page limit for Challenges 1 - 4 and Challenge 5, respectively.) Please use APA style for citations and references.			Solution Submission Instructions and Template			Solution Submission Instructions and Template
13162	ASPIRE Design Challenge 5: Integrated Solution for Translational Innovation in Pain, Opioid Use Disorder and Overdose	Summary of NCATS ASPIRE Design ChallengesSummary of NCATS ASPIRE Design Challenge 5: Integrated Solution for Translational Innovation in Pain, Opioid Use Disorder and OverdoseHow to EnterDates and DeadlinesThe IC’s Statutory Authority to Conduct the ChallengeSubject of the Challenge CompetitionConcurrent Companion NCATS ASPIRE Design ChallengesRegistration Process for InnovatorsThe PrizeEvaluation and Winner SelectionBasis upon Which Submissions Will Be EvaluatedSummary of NCATS ASPIRE Design ChallengesThe National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH), is inviting novel design solutions for A Specialized Platform for Innovative Research Exploration (NCATS ASPIRE) Design Challenges as part of the NCATS ASPIRE Program. The goal of the NCATS ASPIRE Design Challenges is to reward and spur innovative and catalytic approaches toward solving the opioid crisis through development of (1) novel chemistries, (2) data mining and analysis tools and technologies, and (3) biological assays that will revolutionize discovery, development and preclinical testing of next-generation, safer and non-addictive analgesics to treat pain, as well as new treatments for opioid use disorder (OUD) and overdose. The first phase of these prize competitions is implemented through a suite of concurrent companion Design Challenges that comprises separate Challenges for each of four areas — chemistry database, electronic laboratory knowledge portal for synthetic chemistry, algorithms and biological assays — and an additional Challenge for a combined solution to at least two Challenge areas. At this stage, innovators are expected to submit designs, not final products or prototypes.NCATS envisions following these Design Challenges with a follow-on but distinct final Reduction-to-Practice Challenge, which will aim to invoke further scientific and technological development of the model system. Winners of the Design Challenges will be invited to present their designs so that, in the envisioned follow-up Reduction-to-Practice Challenge, an open competition, teams will be able to form multidisciplinary collaborations to advance and integrate the most feasible and promising approaches to the multiple Challenges into a single integrative platform. Innovators will be invited to demonstrate final solutions.The NCATS ASPIRE Design Challenges are part of NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative will bolster research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative.NCATS refers to participants in the NCATS ASPIRE Design Challenges as “innovators,” because all solutions will require highly innovative approaches to achieve success. Innovators should clearly state how and why the proposed solution would provide significant advances over currently available tools. Innovators may choose to compete in one or more individual Challenges to address a single area (Challenges 1-4) or propose a combined solution for at least two Challenge areas (Challenge 5).Back to topSummary of NCATS ASPIRE Design Challenge 5: Integrated Solution for Translational Innovation in Pain, Opioid Use Disorder and OverdoseChallenge 5 aims to reward and spur the design of innovative, comprehensive solutions to the opioid crisis through innovative approaches that integrate solutions to at least two Challenge areas (Challenges 1-4: Integrated Database, Electronic Synthetic Chemistry Portal, Predictive Algorithms and Biological Assays, respectively) into a single platform.The goal of this Challenge is to converge solutions to at least two Challenge areas (Challenges 1-4: Integrated Database, Electronic Synthetic Chemistry Portal, Predictive Algorithms and Biological Assays, respectively) from the very beginning into an Integrated Solution. As with the individual NCATS ASPIRE Design Challenges, an Integrated Solution is expected to incorporate each of the requirements and desired features as detailed in the individual Challenge areas. This Challenge requires submission of only a detailed description of the design of the integrated solution, not the final working integrated solution. In addition, while individual components may be operating from different locations, the functionality and degree of integration of the components in the Integrated Solution will be evaluated. It is anticipated that this Challenge would require a large, multi-expert team that is likely to be in multiple locations. Hence, a plan should be included that describes how the team will be structured and how the exchange of knowledge, ideas and implementation of solutions will be facilitated among the participating sites.Evaluation criteria that reviewers will be asked to address are specified below.Back to topDates and DeadlinesSolutions must be submitted to Challenge.gov by NOON Eastern Time on May 31, 2019. The Challenge begins: December 31, 2018 Submission period: December 31, 2018-May 31, 2019Judging period: June 17, 2019-August 2, 2019Winners announced: August 2019For further information send an email to NCATSASPIREChallenge@mail.nih.gov.Back to topThe IC’s Statutory Authority to Conduct the ChallengeThe general purpose of NCATS is to coordinate and develop resources that leverage basic research in support of translational science and to develop partnerships and work cooperatively to foster synergy in ways that do not create duplication, redundancy and competition with industry activities (42 USC 287(a)). In order to fulfill its mission, NCATS supports projects that will transform the translational process so that new treatments and cures for diseases can be delivered to patients faster by understanding the translational process in order to create a basis for more science-driven, predictive and effective intervention development for the prevention and treatment of all diseases. NCATS is also conducting this Challenge under the America Creating Opportunities to Meaningfully Promote Excellence in Technology, Education, and Science (COMPETES) Reauthorization Act of 2010, 15 U.S.C. 3719. In line with these authorities, this Challenge(s) will lead to innovative designs for developing technology to revolutionize discovery, development and preclinical testing of new and safer treatments of pain, opioid use disorder (OUD), and overdose; the result will be generalizable tools that will be widely available to fill longstanding gaps that have impeded the marriage of basic and translational sciences.Back to topSubject of the Challenge CompetitionChallenge 5. Integrated Solution for Translational Innovation in Pain, Opioid Use Disorder and Overdose. The goal of this Challenge is to converge solutions to at least two component Challenge areas (Challenges 1-4: Integrated Database, Electronic Synthetic Chemistry Portal, Predictive Algorithms and/or Biological Assays, respectively) from the very beginning into an Integrated Solution. As with the individual NCATS ASPIRE Design Challenges, an Integrated Solution is expected to incorporate each of the requirements and desired features as detailed in the individual Challenge areas. In addition, while individual components may be operating from different locations, the functionality and degree of integration of the components in the Integrated Solution will be evaluated. This Challenge requires submission of only a detailed description of the design of the integrated solution, not the final working integrated solution. It is anticipated that this Challenge would require a large, multi-expert team that is likely to be in multiple locations. Hence, a plan should be included that describes how the team will be structured and how the exchange of knowledge, ideas and implementation of solutions will be facilitated among the participating sites.Component Area 1 relates to the design of an open-source, controlled-access database that incorporates all currently available chemical, biological and clinical data of known opioid- and non-opioid-based analgesics, drugs of abuse and drugs used to treat drug abuse.Component Area 2 relates to the design of a next-generation open source electronic lab notebook (eLN) that collects, organizes and analyzes data relevant to the chemical synthesis and analyses of known opioid- and non-opioid-based analgesics, drugs of abuse and molecules used to treat drug abuse into an electronic laboratory knowledge portal for synthetic chemistry (electronic synthetic chemistry portal; eSCP).Component Area 3 relates to the design of open-source, advanced machine learning algorithms that would facilitate the discovery of novel, efficacious and non-addictive analgesics and/or treatments for drug abuse by utilizing the data collected in open-source databases (Challenge area 1), eSCPs (Challenge area 2), and biological assays (Challenge area 4).Component Area 4 relates to the design of novel, physiologically relevant biological assays that accurately replicate the safety profile and effectiveness of existing drugs to treat addiction and/or overdose and that can be reliably used in predictive risk assessments of new analgesics or drugs to treat addiction and/or overdose and/or be able to anticipate the degree of addictiveness of an analgesic prior to clinical testing.Back to topConcurrent Companion NCATS ASPIRE Design ChallengesNCATS has recently explored the development of A Specialized Platform for Innovative Research Exploration (ASPIRE) to aid in the discovery and development of novel and effective treatments while at the same time making the process faster and more cost-effective. The NCATS ASPIRE Program aims to develop and integrate automated synthetic chemistry, biological screening and artificial intelligence approaches in order to significantly advance our understanding of the relationship between chemical and biological space and enable further access into biologically relevant chemical space. The platform will utilize currently available knowledge to develop innovative algorithms and predict and synthetize novel structures capable of interacting with specific targets; enable small-scale synthesis of the predicted molecules; and incorporate in-line, rapid biological testing of the molecules. Any new data obtained through this process would then be fed back into the system to further improve design, synthesis and biological characteristics of molecules.Over 25 million people in the United States experience pain every day (2012 National Health Interview Survey data) and need safe, addiction-free treatments to alleviate their suffering. This clinical demand is of tremendous importance given that overprescribing of opioids for managing acute and chronic pain has fueled the current epidemic of opioid use disorder and overdose deaths, and the effectiveness of opioids for long-term pain management is being questioned. Safe, effective and non-addictive drugs (small molecules and biologics) to treat pain, mitigate addiction and reverse overdose are key to addressing the opioid crisis. Given failures and limitations of previous drug development efforts, drugs that recognize novel targets, have novel structures and can be identified in human-based, physiologically relevant in vitro systems are needed. To advance the NCATS ASPIRE Program and reward and spur innovative solutions to the development of new drugs for pain, addiction and overdose, NCATS is issuing this Challenge and concurrent companion Challenges to highly collaborative innovators interested in designing novel approaches that would lead to efficacious and non-addictive pain treatments and/or novel treatments for addiction and overdose.The ultimate goal of the NCATS ASPIRE Program is development of a platform that a wide spectrum of scientists can use to advance their translational science relevant to development and preclinical testing of new and safer treatments of pain, opioid use disorder (OUD) and overdose. Furthermore, it is essential that the approaches described and proposed here are applicable to any translational problem.Challenge 1: Integrated Chemistry Database for Translational Innovation in Pain, Opioid Use Disorder and Overdose rewards and spurs innovative solutions to the design of an open-source, controlled-access database that incorporates all currently available chemical, biological and clinical data of known opioid- and non-opioid-based analgesics, drugs of abuse and drugs used to treat drug abuse.Challenge 2: Electronic Synthetic Chemistry Portal for Translational Innovation in Pain, Opioid Use Disorder and Overdose rewards and spurs innovative solutions to the design of a next-generation open-source electronic lab notebook (eLN) that collects, organizes and analyzes data relevant to the chemical synthesis and analyses of known opioid- and non-opioid-based analgesics, drugs of abuse and molecules used to treat drug abuse into an electronic laboratory knowledge portal for synthetic chemistry (electronic synthetic chemistry portal; eSCP).Challenge 3: Predictive Algorithms for Translational Innovation in Pain, Opioid Use Disorder and Overdose rewards and spurs innovative solutions to the design of open source, advanced machine learning algorithms that would facilitate the discovery of novel, efficacious and non-addictive analgesics and/or treatments for drug abuse by utilizing the data collected in open source databases (Challenge area 1), eSCPs (Challenge area 2) and biological assays (Challenge area 4).Challenge 4: Biological Assays for Translational Innovation in Pain, Opioid Use Disorder and Overdose rewards and spurs innovative solutions to the design of novel, physiologically relevant biological assays that accurately replicate the safety profile and effectiveness of existing drugs to treat addiction and/or overdose and that can be reliably used in predictive risk assessments of new analgesics or drugs to treat addiction and/or overdose and/or be able to anticipate the degree of addictiveness of an analgesic prior to clinical testing.Note: Each component of Challenge 5 (above) is also available as an individual Challenge at Challenge.gov.Back to topRegistration Process for InnovatorsInnovators may access the registration and submission platform in one of the following ways:Access www.challenge.gov and search for “NCATS ASPIRE Design Challenge”Back to topThe PrizeAmount of the Prize; Award-Approving Official. The total prize purse is $500,000. Up to five (5) winners will be selected. NIH reserves the right to cancel, suspend and/or modify this Challenge at any time through amendment to this notice. In addition, NIH reserves the right to not award any prizes if no solutions are deemed worthy. The Award Approving Official will be Christopher P. Austin, M.D., Director of the National Center for Advancing Translational Sciences (NCATS).Payment of the Prize. Prizes awarded under this competition will be paid by electronic funds transfer and may be subject to federal income taxes. HHS/NIH will comply with the Internal Revenue Service withholding and reporting requirements, where applicable.Matching Requirement. A for-profit private entity solver (innovator) receiving a prize under this Challenge must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018. Such a winner(s) will be required to demonstrate that matching funds and/or in-kind contributions were committed to achieve the winning solution. Such a winner(s) must identify the source and amount of funds used to meet the matching requirement or describe how the value for in-kind contributions was determined.Back to topEvaluation and Winner SelectionBasis upon Which Winners Will Be Selected. A panel of federal and non-federal reviewers, with expertise directly relevant to the Challenge, will evaluate the solutions based on feasibility and ability to achieve the criteria listed below. The solutions and evaluation statements from the technical panel will then be reviewed by federal employees serving as judges, who will select the Challenge winners, subject to the final decision by the Award Approving Official. The NCATS will provide feedback from the technical experts and judges to the winners and non-winners on their respective submissions.The points assigned to each set of evaluation criteria are guidelines from NCATS to suggest which scientific milestones are of emphasis and interest to the Center. All winners are highly encouraged to participate in future NCATS ASPIRE Reduction-to-Practice Challenges that NCATS is planning. Only complete submissions will be reviewed.Submission Requirements and TemplateInstructions for submission: Please format the proposal using the Submission Template and submit it to Challenge.gov as a PDF. Brief instructions on the submission process can be found below. Detailed instructions are provided in the submission template.Back to topBasis upon Which Submissions Will Be EvaluatedChallenge 5. Integrated Solution for Translational Innovation in Pain, Opioid Use Disorder and Overdose. The goal of this Challenge is to converge component areas 1, 2, 3 and 4 (Integrated Database, Electronic Synthetic Chemistry Portal, Predictive Algorithms and Biological Assays, respectively) from the very beginning into an Integrated Solution. As with the individual NCATS ASPIRE Design Challenges, an Integrated Solution is expected to incorporate each of the requirements and desired features as detailed in the individual Challenge areas. In addition, while individual components may be operating from different locations, the functionality and degree of integration of the components in the design of the Integrated Solution will be evaluated. It is anticipated that this Challenge would require a large, multi-expert team that is likely to be in multiple locations.Judging criteria:Evaluation Criterion 1: Overall Impact and Innovation (30 points)How innovative is the proposed combined solution overall?What is the potential impact of the proposed solution on the development of novel treatments for pain, opioid use disorder (OUD) and/or overdose?What are major strengths and weaknesses of the combined solution proposed?Are the proposed solutions to the Challenge areas well integrated and synergistic?How likely is it that the integrated solutions can be successful in addressing the multiple Challenge areas and be successful in the Reduction-to-Practice phase?Does the team represent an outstanding group of innovators with a wide spectrum of expertise that can tackle multiple problems simultaneously?Did the team identify potential roadblocks and suggest additional expertise they would utilize to facilitate resolutions?Evaluation Criterion 2: Design of Individual Components (up to 200 points total- up to 50 points for each single component)Each single component of an integrated solution will be evaluated as indicated below:Component 1: Integrated Chemistry Database for Translational Innovation in Pain, Opioid Use Disorder and OverdoseSub-Criterion 1: Impact and Innovation (20 points)Given that innovation is considered using a groundbreaking or paradigm-shifting approach or using existing approaches in an innovative way, to what degree is the proposed design innovative, creative and original?How feasible is the proposed approach, and what is the likelihood of the approach to succeed?Has the innovator or team of innovators demonstrated that appropriate expertise was utilized during development of the design?If team members are at different locations, how well was exchange of knowledge, ideas and solutions facilitated among team members?To what extent does the proposed solution provide the required information necessary for development of novel treatments and therapies for pain, drug addiction and/or overdose?Sub-Criterion 2: Data Complexity, Accuracy, and Interconnectivity (20 points)How well does the database design integrate multiple data sources?Are all the data annotated by source/reference?How well is structural and functional variability/complexity of currently available pain drugs, opioids and treatments for addiction and overdose represented in the database?Do the collected data meet the FAIR requirements (findable, accessible, inter-operable, and reusable: https://www.nature.com/articles/sdata201618)?How well have the innovators defined standards for data types, format, quality, curation, annotation, and common data elements so that data sets are mineable and comparable?Is adequate online back-end infrastructure such as storage and cloud computing capability available?To what extent have the innovators developed a framework for enabling meaningful comparisons across heterogeneous data sets, including individual and population comparisons at the intra- and interspecies levels?Have the innovators designed tools to harmonize disparate data formats?Sub-Criterion 3: Data Accessibility (10 points)Will all study materials, data and procedures be made broadly available and readily accessible to the research community (e.g., are plans for transitioning the database to be publicly accessible included in the solution)?Have the innovators designed a web portal front-end or complete API that enables clear and easy management and retrieval of data and tools and is accessible to the general scientific community across a variety of platforms?How well is the database design documented with a broad extensible format that allows for broader contextual relationships?Have the innovators proposed appropriate tools for batch data retrieval to allow independent computation of the data on the user end?How well have the innovators designed strategies for data curation and updates (e.g., how will new data be incorporated)?Does the solution adequately address how it will remain compliant with data privacy regulations, specifically those that are obtained from human subjects?Component 2: Electronic Synthetic Chemistry Portal for Translational Innovation in Pain, Opioid Use Disorder and OverdoseSub-Criterion 1: Impact and Innovation (20 points)To what extent is the proposal innovative? That is, to what extent does it involve a novel eSCP design or an approach that significantly upgrades and appropriately modifies an existing eLN?Has the innovator or team of innovators demonstrated that appropriate expertise was utilized during development of the design?If team members are at different locations, how well was exchange of knowledge, ideas and solutions facilitated among team members?Have the innovators consulted potential user laboratories with regard to the kind, depth and breadth of data the users desire to have in an eSCP, data standards and formats?How well have innovators optimized the molecular design capabilities of the portal to advance the highest quality hypothetical attributes of target molecules and their proposed synthetic execution plan?To what extent will the data collected enable further mechanistic understanding that is essential to control and optimize chemical reactions so that byproducts are reduced, yields are increased and reaction specificities are improved?Is the eSCP designed to utilize high-quality data from both positive and negative experiments for future discovery and development of novel structures and chemistries of relevance to the treatment of pain and opioid use disorder?Have the innovators adequately described how the eSCP’s application will be demonstrated in laboratories in the envisioned follow-up NCATS ASPIRE Reduction-to-Practice Challenges?While the focus of this Challenge is on pain-related drugs, to what extent is the eSCP designed to be adaptable to collect any kind of chemical and biological data relevant to any future translational Challenge?Are all deposited data, including chemical structures, in a format that can be easily accessible to advanced machine learning algorithms and/or applications?Sub-Criterion 2: Data Collection, Analysis and Integration (20 points)How well does the eSCP pare reaction information to include precise, unambiguous ontological annotation and reaction role descriptors (e.g., solvent, catalyst, other specific additive roles, etc.)?How well is this information organized — for example, is this information organized in a manner to provide comprehensive reaction analytics (similar but not limited to breakdown of reaction types represented; most commonly used reagents and catalysts; time related patterns associated with reaction development, including reaction networks that summarize typical reaction steps and reaction pathway associations with common intermediates or final targets)?Are reactions atom mapped or sequenced in a manner to allow use in retrosynthetic applications or reaction templating?How does the proposed solution permit the broad-scope assessment of the database around the technology or methodology used (e.g., C-H activation, photochemistry, etc.) or highlight the overreliance on specific transformations (e.g., Suzuki reaction)?How effectively and intuitively are the data collected and presented during the work process?How extensible are the data structures (e.g., possible to collect more than one measurement in a set of conditions or parameters)?How rigorously is reaction information parsed and annotated?What chemical representation and data storage standards are used?How precisely and systematically is reaction ontology being captured?What provisions are included for executing reaction analytics (similar but not limited to top reagents used that week with total amount used; rank order listing of reaction types run, by yield or popularity; number of new compounds synthesized/registered, etc.)?How well does the solution provide a customizable analytics dashboard to follow any number of metrics across the entire eSCP (similar but not limited to total reactions that day, total users active, number of compounds submitted to biological assays, etc.)?How is chemical yield information captured?How are reaction entry errors captured and corrected?How well is reagent selection and inventory management integrated?How well is parallel experimentation implemented?What methods exist for importing and exporting chemical information as well as reaction design and execution criteria, and what data formats are supported?How efficiently can experiments be designed, entered and annotated?What provisions exist for applying custom business rules (e.g., requirements for initiating or closing out an experiment)?How well can the eSCP be controlled by or operated from another application (i.e., is a fully documented API or CLI provided)?How well are experimental success and failures tracked?To what extent does the eSCP facilitate validation and reproducibility of experimental data?How are upgrades to the modular eSCP expected to be applied?How well can the eSCP integrate chemical data with those from biological screening assays?What rigor is applied to the capture and storing of data, and what tools are provided to examine the data integrity? (That is, are reagents appearing in the right rows in a consistent fashion? Can the eSCP distinguish or make alerts when solvents, reagents or catalysts are omitted? Is reagent container identification included or captured? Are the data well ordered such that when the same reagent shows up in multiple reactions, it shows up in the same relevant row in the database?)What methodology is present in the eSCP to allow for a plug-and-play template format that can be used to record, extract and report the data?How easy is it to extract the data from the eSCP document and record in database tables with appropriate metadata suitable for mining and analysis with advanced machine learning applications?How well does the eSCP integrate retrosynthetic tools, machine learning and computational chemistry tools in a manner that facilitates future upgrades and additional links to bioassay data and related chemical structure and synthesis information?Sub-Criterion 3: Accessibility and User-Friendliness (10 points)Is this an open-source eSCP solution?How appealing are user interfaces, and how well are they designed for intuitive use?How well does the eSCP facilitate intra- and inter-laboratory connectivity and intra- and inter-laboratory reproducibility?To what degree is the eSCP’s interface user-friendly and in a form that reduces training and increases user acceptance?How well are non-routine documentation options included in the eSCP (for example, tables, textboxes, formulas, etc.)?Is the eSCP remotely accessible? (e.g., off-site computers or mobile devices)Does the eSCP include documentation and management of laboratory chemical/sample inventory, equipment management, usage and label printing and barcodes?How well is the problem of multiple terminologies dealt with? For example, are dictionaries included?Component 3: Predictive Algorithms for Translational Innovation in Pain, Opioid Use Disorder and OverdoseSub-Criterion 1: Impact and Innovation (20 points)Given that innovation is considered using a groundbreaking or paradigm-shifting approach or using existing approaches in an innovative way, to what degree is the proposed design innovative, creative and original?To what extent is the proposed approach feasible, and how high is its likelihood to succeed?Has the innovator or team of innovators demonstrated that appropriate expertise was utilized during development of the design?If team members are at different locations, how well was exchange of knowledge, ideas and solutions facilitated among team members?Have the innovators established their own initial training datasets that can be used to demonstrate the algorithms’ functionality on the set?Does the training data set include structurally diverse compounds?To what extent have the innovators demonstrated why/how the proposed solution can outperform existing algorithms?How well has the proposed solution demonstrated its ability to provide critical information necessary for the development of novel treatments and therapies for pain, drug/addiction and/or overdose?Sub-Criterion 2: Algorithm Design Functionality and Implementation (20 points)How well are the algorithms documented for completing a task on a training set and making predictions on a new set of compounds? (Are the steps precisely stated?)To what extent are the algorithms implemented with open-source codes/packages or commercial software packages?Have the innovators provided a web portal or tool/platform that is accessible to research community to run the proposed algorithms and generate predictions on their compounds of interest?How well have the innovators explained how their algorithms meet the criteria of precision, uniqueness, finiteness, definiteness, input, output and effectiveness?How well can the algorithms identify structural and/or functional similarities in a diverse set of molecules?How well can the algorithms identify specific signatures that may be associated with addiction?How well can the algorithms compare the mechanism of action between multiple drugs and identify structural/functional similarities between them?How successful are the algorithms in identifying structurally diverse drugs with similar pharmacological effect?To what degree can the algorithms provide additional context for drug activity that can be used to identify or anticipate off-target effects?Sub-Criterion 3: Record of Innovation (10 points)How well have the innovators demonstrated experience with creating solutions that:Connect across multiple computational modeling and simulation tools and frameworks;Evaluate and adjust models based on new data as the data become available; andEvaluate and adjust models based on the successes or failures of predicting phenomena observed in humans and, where biologically justified, in animals?Component 4: Biological Assays for Translational Innovation in Pain, Opioid Use Disorder and OverdoseSub-Criterion 1: Impact and Innovation (20 points)To what degree is the proposed assay creative, original and biologically relevant?To what extent is the assay design feasible? Does it have a high likelihood of success?To what extent is the proposed solution innovative, and how high is its potential to significantly improve the state of science?To what extent will the proposed assay accelerate discovery, development and preclinical testing of new and safer treatments of pain and/or opioid use disorder (OUD) and overdose?To what extent are novel concepts, approaches, methodologies and technologies proposed or are existing approaches applied to the design in a novel way?To what extent does the proposed assay incorporate cross-disciplinary techniques (e.g., cell biology, imaging, electronics, engineering, etc.)?Is the proof-of-concept data using currently available pain drugs, drugs of addiction and/or addiction/overdose treatments proposed?How well does the assay(s) demonstrate biological and physiological relevance to a specific application (pain, addiction or OUD)?Sub-Criterion 2: Model System and Assay Design (20 points)How physiologically relevant is the proposed model system that is being assayed?To what extent is the assay designed and amenable for validation taking into consideration the target being studied using appropriate drugs/compounds and controls?Are the appropriate cell types co-cultured in the model system at physiological ratios? What is the origin of the cells, and how relevant are the cell types to the model system?What is the assay’s readout (e.g., biochemical, fluorometric, phenotypic), and is this sufficient to maximize the value of the assay?How long will it take to perform the assay in full? Is the timing of the assay appropriate? (What is an assay’s development cycle time?)How many technical replicates will the assay support?Can the assay be multiplexed?Are secondary/specificity/selectivity assays proposed to confirm the initial data?What are instrumental, computational and data storage requirements?Sub-Criterion 3: Assay Robustness, Reproducibility and Scalability (10 points)How well does the proposal describe plans to assess inter- and intra-laboratory utility, transferability and reproducibility?How well are the protocols described? Are the protocols sufficiently clear and detailed to facilitate inter- and intra-laboratory utility and reproducibility?Is the assay designed to minimize bias — for example, are the cells seeded, differentiated and cultured manually?Are appropriate experiments proposed that will address the stability of the assay components and reagents?To what extent are the data collection and analysis automated?To what degree could the assay be integrated with other Challenge(s) in a subsequent reduction-to-practice phase?Evaluation Criterion 3: Integration, Adaptability, User-Friendliness and Accessibility (20 points)How well is each of the single components (Integrated Database, Electronic Synthetic Chemistry Portal, Predictive Algorithms and/or Biological Assays) integrated in the overall solution?What are major strengths and weaknesses of the overall solution proposed?Which component(s) are the most and least developed?How likely is it that any weaknesses in the approach/design can be successfully addressed?To what degree is the proposed solution adaptable to future translational problems, beyond those focusing on treatments of pain, opioid use disorder (OUD) and overdose?To what degree are the basic principles amendable to additional and/or new translational questions?How user-friendly are the proposed individual components and the integrated platform as a whole?Are there possibilities to further simplify the proposed approaches/processes in the subsequent Reduction-to-Practice phase?To what extent are there features incorporated or planned to be incorporated that would allow remote access to the platform?To what is extent is the team strongly focused on user-friendliness and dedicated to simplifying the solution for eventual use by non-expert scientists?Back to top			Aspire Design Challenge 5			Aspire Design Challenge 5

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