Human-Based New Approach Methodologies for Biomedical Research

Submission period: Open until 01/11/24 11:59 PM EST

Challenge types: #Ideas #Analytics #visualizations #algorithms #Scientific #Biomedical #Biomedicine #Models #simulation #CellFree #molecular #physiology

Total cash prizes:$1,000,000

Application Portal: Challenge.Gov

Subject of the Challenge:

Seize this unprecedented opportunity to redefine biomedical research. Collaborate, innovate, and develop transformative methodologies that resonate with human biology, transcending traditional approaches. Your innovations will pave the way for human-based research solutions that can transform how safety and efficacy studies and human disease modeling can be conducted. Envision a future where multiscale mathematical models, AI-driven approaches, and intricate cell-based constructs coalesce to revolutionize our understanding of health and disease. With $1,000,000 in prizes, the NIH is seeking your ideas that will help demonstrate new ways of conducting basic research, uncovering disease mechanisms, and translating knowledge into products and eventually into practice.

Background

The 21st century has been a time of expeditious technological advancement, with increasing use of new and evolving methodologies including, but not limited to, gene editing approaches, artificial intelligence (AI), multiscale mathematical approaches, tissue engineering approaches, and novel chemistry, sensing, and imaging technologies that are enabling new ways to conduct science. These technologies and other advances hold tremendous promise in understanding fundamental biology and advancing human health. Additionally, these technologies drive innovation in scientific methodologies themselves, opening doors to new scientific approaches.

The NIH Common Fund recognizes the pivotal moment we are in, a juncture where rapid technological advancement meets the pressing need for New Approach Methodologies (NAMs). Twenty-first-century technological advancements have ushered in unparalleled scientific progress, not only transforming the way we approach scientific inquiries but broadening our horizons, offering tools that could potentially replace or complement traditional models in certain areas, expand research laboratory capabilities, and potentially translate into improving human health in new ways. While animal models currently remain indispensable for research, there is a growing realization that alternative models, such as microphysiological systems and digital models, could offer unique advantages. They could provide key insights into human biology and answer complex biomedical questions with greater precision. However, human-based NAMs are relatively young in the field of biomedical research and must advance to be truly transformative. Current in vitro models do not recapitulate or emulate all the complexity of physiologic and pathophysiologic processes and cellular networks in disease. The in silico and biophysical models are limited in accurately predicting complex biological processes and clinical symptoms. The journey towards realizing the full potential of these NAMs demands collaboration across disciplines. This is an endeavor where biologists, engineers, data scientists, and many other experts can unite their expertise to create innovative solutions with relevance to human biology.

The evolution from traditional to modern methodologies is not only about technological progression. It reflects a broader shift in the biomedical landscape influenced by economic and regulatory developments. The cost-effectiveness of new methods, combined with regulatory encouragement, has amplified the momentum toward innovative research approaches. Additionally, the fusion of diverse fields — from computational sciences to engineering — with biomedical research is enabling a more holistic approach, redefining the boundaries of what is possible. This interdisciplinary synergy is central to the promise of NAMs, underscoring the importance of collaboration in pioneering solutions that could redefine our understanding of human biology. Amid this transformation, the scientific community stands on the brink of a new era, driven not just by the quest for knowledge but by the aspiration to reshape the very fabric of biomedical research.

The NIH is embarking on the bold, difficult, and necessary mission to develop and deploy an integrated set of NAMs that is human-based and would ultimately enable their use in precision medicine across the lifespan. The NIH Common Fund is hosting this challenge as part of the strategic planning process. The NIH Common Fund has the goal of catalyzing the development, standardization, validation, and use of human-based NAMs that will transform basic, translational, and clinical sciences. The goals would be: 1) to model and understand human health and disease outcomes across diverse populations; 2) to develop NAMs that provide insight into disease and specific biological processes; 3) to validate the use of NAMs that will support standardization and regulatory acceptance, and 4) to complement or replace existing traditional models and enhance the efficiency and effectiveness of biomedical research.

The Challenge

This challenge seeks to propel the development and refinement of human-based NAMs. ?While traditional?models continue to be vital to advancing scientific knowledge, NAMs offer unique strengths that, when utilized correctly or in combination, can expand the toolbox for researchers to answer previously difficult or unanswerable biomedical research questions: https://grants.nih.gov/grants/policy/air/alternatives

Solutions must include next-generation innovation in in vitro, in silico, or in chemico approaches to emulate human biology or integrations thereof. Solutions must demonstrate substantial advancement from the current state-of-the-art technologies.

Challenge participants will submit a 15-page whitepaper demonstrating:

Innovation in In Vitro Modeling: Develop advanced human-derived, cell-, or tissue-based models that represent human physiological and pathophysiologic processes across the lifespan. These models should replicate intricate biological reactions and architectural structures, thereby serving as effective platforms for testing, analysis, and prediction. Some capabilities of these solutions are (but are not limited to):

• Demonstrate the ability to model the complexities of human population diversity.
• Catalyze the development of NAMs of sufficient complexity to address a more complicated context of use that is not attainable by current NAM models, such as vascular, neural, immune, and/or microbiome components.
• Incorporate complex immune function in microphysiological Systems (MPS) for emulating immune-related pathways and environmental triggers in inflammatory and autoimmune conditions.
• Standardize functional assays to assess the physiological relevance of the models.
• Utilize patient-derived cells or tissues to develop personalized models.?
• Use gene-editing techniques like CRISPR to introduce specific mutations into your in vitro models to study disease mechanisms.

Powering In Silico Models and Simulations: Harness the capabilities of computational tools to create models that can simulate biological responses. These in silico models, backed by robust algorithms, should be capable of analyzing complex datasets, predicting possible outcomes, and aiding in decision-making processes in biomedical research. Some capabilities of these solutions are (but are not limited to):

• Simulate health and model key disease states or pathological changes (e.g., chronic inflammation, mitochondrial dysfunction, mutation accumulation, etc.)
• Develop the ability for real-time incorporation of real-world clinical data and insights to fine-tune simulations, improving their predictive accuracy.
• Utilize generative models to design synthetic biological systems or pathways for robust testing and validation.
• Demonstrate the ability to model the diversities of the human population.
• Develop computational models that can accurately simulate metabolic reactions in cells, providing insights into disease pathways.
• Develop virtual clinical trial approaches that use simulations to predict how human populations might respond to a new drug or treatment, enabling informed clinical trial designs.

Exploration of In Chemico Systems: Venture into the realm of cell-free systems that allow researchers to study molecular interactions outside the confines of cellular environments. These systems should provide a clear window into the intricate interactions of molecules, enabling precise studies without cellular interference. Some capabilities of these solutions are (but are not limited to):

• Ability to capture and control dynamic epigenetic, biochemical, and genetic changes.
• High-throughput assays to query biologically relevant molecular properties.
• Incorporate advanced analytical methods to assess the full range of metabolic and proteomic changes in reaction conditions.
• Include cell-free expression systems as alternatives to production of biologics including those with non-natural functionalities.
• Implement nanotechnology to manipulate molecular interactions at an incredibly small scale.

NAM Integration: The challenge emphasizes integration of NAMs, either across models or into other platforms. The idea is to create a cohesive solution that leverages multiple methodologies for a comprehensive insight into human biology. Some examples of these solutions are (but are not limited to):

• Development of patient or population-level digital twins with other NAMs
• Integration of NAMs with diagnostic platforms for informed decision-making in the clinical setting (i.e., learning healthcare systems)
• Integration of AI/machine learning (ML) with other NAMs to develop predictive models
• Integrated AI and in chemico NAMs that can capture the vast complexities (e.g., socioeconomic status, diet, chemical exposure, social media interactions, etc.) in the environment around individuals and populations (i.e., exposome).?
• Multi-tissue MPS coupled with AI-based governing tools and in chemico monitoring components to rapidly evaluate and adjust MPS parameters to model an individuals’ unique physiology and pathophysiology.
• Implement AI-based decision support systems that can perform real-time analysis of data from various NAMs to assist clinicians and researchers in making more informed decisions.

Each submission should contain a detailed explanation of the proposed methodology's design, its potential applications, and most importantly, the rationale for its effectiveness. It is crucial to elucidate the challenges that could be encountered during the development phase, the strategies employed to overcome them, and the innovations introduced. Any datasets included should align with ?FAIR principles, ensuring they are easily findable, accessible, interoperable, and reusable. If AI or ML models are employed, their design, accuracy metrics, and utility should be clearly detailed. To address these hurdles, the transformative NAMs proposed under this initiative must demonstrate substantial advancement compared to current approaches in challenge areas by developing innovative and integrative approaches that, for example, emulate/mimic complex biological structures/processes. Solutions should further enable the study of human-based NAMs to advance human relevance in biomedical research. For this challenge competition, solutions that include small animal models and other non-mammalian species will be considered out of scope.

Examples of general challenge areas for all NAMs in need of testable and feasible solutions include, but are not limited to:

• Representing diversity in human populations in modeling disease or health outcomes (e.g., diverse genetic ancestries, age groups, sex as a biological variable [SABV], socioeconomic status, health disparities, social determinants of health [SDOH])
• Modeling complex human physiology (e.g., #pregnancy, #development, metabolic, immune, neurosensory, age-related changes) and characterizing long-term, systemic, and developmental health effects of environmental and drug exposures (i.e., DOHaD)
• Areas of high need for alternative models (e.g., #rare #diseases, rare #cancer , #psychiatric #disorders, #ophthalmology, #pediatrics, #aging, #reproductivehealth, #infectiousdiseases, #neuroscience, and #behaviorresearch)
• Testing in complex systems for non-clinical data needed for first-in-human or first-in-population trials (e.g., dose-ranging, toxicology)
• Developing, standardizing, and manufacturing of platforms for in vitro, in chemico, and in silico approaches and the integration of such platforms for advancing NAMs for regulatory acceptance
• Validation and standardization of NAMs to enable robust, reliable, and reproducible research
• Global harmonization across the many stakeholders (e.g., academia, industry, regulatory agencies) for widespread use and adoption of NAMs

While the introduction of a novel methodology is a significant advance, this challenge seeks more than just innovation. It aims to find solutions that bridge existing gaps in biomedical research to improve human health. Winning entries will not only showcase a novel approach but will also support its potential impact in the real world. A thorough understanding of human biology, the relevance of the innovation in the current research landscape, and its scalability are factors that will be pivotal in the evaluation process. In essence, the challenge is not just about proposing a solution, but about influencing the foreseeable future of biomedical research.

Statutory Authority to Conduct the Challenge: The NIH Common Fund is a component of the NIH budget which is managed by the Office of Strategic Coordination, Division of Program Coordination, Planning, and Strategic Initiatives, Office of the Director. Common Fund programs address emerging scientific opportunities and pressing challenges in biomedical research that no single NIH Institute or Center (IC) can address on its own but are of high priority for the NIH as a whole [42 U.S.C. 282a(c)(1)]. The NIH Office of the Director is conducting this challenge under the America Creating Opportunities to Meaningfully Promote Excellence in Technology, Education, and Science (COMPETES) Reauthorization Act of 2010, as amended [15 U.S.C. § 3719]. This Challenge is consistent with and promotes the agency’s mission by catalyzing the goal-driven development of innovative tools and technologies with the potential to enhance human health.

Award Approving Official: The Award Approving Official will be the Director of the Office of Strategic Coordination within the Division of Program Coordination, Planning, and Strategic Initiatives in the NIH Office of the Director.

Payment of the Prize: Prizes awarded under this Challenge 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. All entities (institutions, universities, companies, etc.) participating in this Challenge are encouraged, but not required, to request and obtain a free Unique Entity ID, if they have not already done so, via SAM.gov as this will expedite prize payment. Additional information can be found at https://sam.gov/content/entity-registration. NIH reserves the right, in its sole discretion, to (a) cancel, suspend, or modify the Challenge, or any part of it, for any reason, and/or (b) not award any prizes if no submissions are deemed worthy.

Timeline

11/07/23 09:00 AM EST: Open for Submissions - Challenge Launch

01/11/24 11:59 PM EST: Submission Deadline

01/12/24 09:00 AM EST: Judging Begins

02/29/24 11:00 AM EST: Winners Announced

Prizes

Total cash prizes

$1,000,000

Prize description

Up to twenty proposals that are judged to best meet the requirements will be awarded up to $50,000 each. The total prize purse for this challenge is $1,000,000.

Rules

Eligibility requirements

Eligibility rules: To be eligible to win a prize under this Challenge, a Participant (whether a Team or an Entity) —

a. Shall have registered to participate in the Challenge under the rules promulgated by the National Institutes of Health (NIH) as published in this announcement.

b. Shall have complied with all the requirements set forth in this announcement.

c. In the case of an Entity, shall be incorporated in and maintain a primary place of business in the United States. In the case of a Team, the Team Leader 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 or Entity 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 or Entity, if applicable, may be recognized when the results are announced.

d. Shall not be a federal entity or federal employee acting within the scope of their employment.

e. Shall not be an employee of the Department of Health and Human Services (HHS, or any other component of HHS) acting in their personal capacity.

f. Who 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.

g. Shall 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).

h. Shall be 18 years of age or older at the time of submission.

Rules

Participation Rules: Participation Rules: (1) Federal grantees and recipients of cooperative agreements or other transaction (OT) awards are eligible to participate in the Challenge but may not use Federal funds from a grant award, cooperative agreement, or OT award to develop their Challenge submission or to fund efforts in support of their Challenge submission unless use of such funds is consistent with the purpose, terms, and conditions of the grant award, cooperative agreement, or OT award. Each Participant (whether participating as a Team or Entity) intending to use Federal grant, cooperative agreement, or OT award funds must register for and participate in the Challenge as an entity on behalf of the awardee institution, organization, or entity. If a winning Participant uses Federal grant, cooperative agreement, or OT award funds to participate in the Challenge, the prize must be treated as program income for purposes of the original grant, cooperative agreement, or OT award in accordance with applicable Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards [2 CFR § 200]. Participants using Federal grant, cooperative agreement, or OT award funds to participate and/or report prize funding as program income (for winning Participants) should coordinate with the awarding official at the federal awarding agency. (2) Federal contractors may not use federal funds from a contract to develop their Challenge submissions or to fund efforts in support of their Challenge submissions. (3) By participating in this Challenge, each Participant (whether participating as a Team or an Entity) agrees to assume any and all risks and waive claims against the federal government and its related entities, 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. (4) Based on the subject matter of the Challenge, the type of work that it will possibly require, as well as an analysis of the likelihood of any claims for death, bodily injury, property damage, or loss potentially resulting from Challenge participation, no Participant (whether participating as a Team or an Entity) participating in the Challenge is required to obtain liability insurance, or demonstrate financial responsibility, or agree to indemnify the federal government against third party claims for damages arising from or related to Challenge activities in order to participate in this Challenge. (5) A Participant (whether participating as a Team or an Entity) shall not be deemed ineligible because the Participant used federal facilities or consulted with federal employees during the Challenge if the facilities and employees are made available to all Participants participating in the Challenge on an equitable basis. (6) By participating in this Challenge, each Participant (whether participating as a Team or an Entity) warrants that they are 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 Participant (or is an improved version of an existing work that the Participant 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 Participant is aware. (7) By participating in this Challenge, each Participant (whether participating as a Team or an Entity) grants to the NIH a nonexclusive, nontransferable, irrevocable, paid-up license to utilize the full contents of the submission for the purposes of informing the design of ongoing or future programs or activities supported by NIH. Additionally, each Participant selected to win a prize award under this Challenge grants to the NIH an irrevocable, paid-up, royalty-free nonexclusive worldwide license to reproduce, publish, post, link to, share, and display publicly the Title, Executive Summary, and Plain Language Summary components of the submission on the web or elsewhere. Each Participant will retain all other intellectual property rights in their submissions, as applicable. To participate in the Challenge, each Participant must warrant that there are no legal obstacles to providing the above-referenced nonexclusive licenses of the Participant’s rights to the federal government. To receive an award, Participants will not be required to transfer their intellectual property rights to NIH, but Participants must grant to the federal government the nonexclusive licenses recited herein. (8) Each Participant (whether participating as a Team or an Entity) agrees to follow all applicable federal, state, and local laws, regulations, and policies. (9) Each Participant (whether participating as a Team or an Entity) participating in this Challenge must comply with all terms and conditions of these rules, and participation in this Challenge constitutes each such Participant’s full and unconditional agreement to abide by these rules. Winning is contingent upon fulfilling all requirements herein. (10) As a condition for winning a cash prize in this Challenge, each Participant (whether participating as a Team or an Entity) that has been selected as a winner must complete and submit all requested winner verification and payment documents to NIH within 7 business days of formal notification. Failure to return all required verification documents by the date specified in the notification may be a basis for disqualification of a cash prize winning submission. (11) By participating in this Challenge, each Participant (whether participating as a Team or an Entity) irrevocably grants to NIH the right to the use of their name, affiliation, city and state, and likeness or image for the purposes of publicity releases and any other promotion of this Challenge.

Judging

Basis Upon Which a Winner Will be Selected: Submissions will first undergo an administrative triage step to review solver eligibility to compete in this Challenge as well as submission completeness and applicability of scope. Complete and applicable submissions from eligible solvers will then be evaluated by a panel composed of scientific and technological experts using the Judging Criteria listed below. A Judging Panel composed of federal employees will review these evaluations and select the winners, pending final decisions by the Award Approving Official. NIH will not make Participants’ evaluation or judging results available to Participants or the public.

• Understanding of the Problem / Scientific Rationale: Explanation of why a novel or improved NAM is needed, potential roadblock(s) to its development, and appropriate solutions are clearly identified. - 30%
• Team: Interdisciplinary expertise of the team or entity submitting the idea. - 10%
• Feasibility: How well the use of NAMs predict outcomes in humans. Soundness of the verification/validation strategy. - 20%
• Innovation: Novelty and innovation of the proposed idea. - 20%
• Potential Impact: Potential impact on strategic planning, advancing use of NAMs in the specified challenge areas, and the potential for the model’s application across multiple areas. - 20%

How to enter

Challenge participants should consist of multidisciplinary teams of experts who are appropriate for their proposed solution. Submit an entry describing the specific challenge area(s), what their proposed solution will address, why a novel or improved NAM is needed, and how it will address the challenge area(s). Submissions will also consist of detailed descriptions of the participant’s team composition and expertise, efficacy of the proposed new approach methodology, scientific rationale, novelty of the idea, and its potential impact. Participants may submit proposed solutions to more than one NAM but must do so with separate proposals that independently address each of the NAMs challenges. To be eligible for an award, your submission must, at minimum:

• Sufficiently satisfy the minimum Judging Criteria requirements.
• Thoughtfully address the Submission Form questions.
• Be scored higher than your competitors!

See the Rules section for specific team/entity eligibility information. Registration and Submission Process: The official challenge announcement for the Complement-ARIE (Complement Animal Research In Experimentation) Challenge can be found on Challenge.gov at https://www.challenge.gov/?challenge=Complement-ARIE. The Challenge registration and submission process is administered by HeroX, a challenge platform and management provider under contract with the NASA Center of Excellence for Collaborative Innovation on behalf of NIH. All interested Participants must register on the official challenge portal by going to https://www.herox.com/Complement-ARIE by the registration deadline on January 11, 2024. Upon registering, participants will be required to identify whether they are registering as either of the following: as an independent Team (i.e., registering as a group of individuals competing together but not on behalf of an established organization, institution, or corporation) or as an Entity (i.e., registering as a group of individuals competing together on behalf of a legally established organization, institution, or corporation). Participants will need to provide the name, affiliation, and contact information of all individuals competing in this Challenge as part of a Team or on behalf of an Entity. All Participants will also be required to acknowledge whether federal funding will be used in the development of the Challenge submission (see Participation Rule 1). All Participants must certify they have read, understand, and agree to abide by the official eligibility rules, participation rules, and requirements for the Challenge as stated in this announcement.

• For Teams: Each participating Team is required to identify a Team Leader who will register and submit on behalf of the Team members. The Team Leader is responsible for all communications with the Challenge sponsors and, in the event of winning a cash prize, will be paid the prize in full. To be eligible to receive a cash prize, the Team Leader must be a citizen or permanent resident of the United States. In the event that a dispute regarding the identity of the Team Leader who actually submitted the entry cannot be resolved to NIH’s satisfaction, the affected submission will be deemed ineligible.
• For Entities: Each participating Entity is required to identify a Point of Contact who will register and submit on behalf of the Entity. The Point of Contact is responsible for all communications with the Challenge sponsors. In the event of winning a cash prize, the prize will be paid directly to the Entity, not to the Point of Contact. To be eligible to receive a cash prize, the Entity must be incorporated in and maintain a primary place of business in the United States. As stated in the Participation Rules, Participants intending to use Federal grant, cooperative agreement, or other transaction (OT) award funds must register for and participate in the Challenge as an Entity on behalf of the awardee institution or organization. In the event that a dispute regarding the identity of the Point of Contact who actually submitted the entry cannot be resolved to NIH’s satisfaction, the affected submission will be deemed ineligible.

Submission Requirements: On the challenge submission website, participants will complete the following fields in their submission form. Submission fields in the form have character limits that will total 15 pages for their entire submission.

• Eligibility Review: Multiple questions to determine the eligibility of the team/entity submitting, as well as confirmation that the team/entity meets and accepts all rules to participate in the challenge.
• Executive Summary: Provide a concise summary of your proposed solution, emphasizing its significance and innovation. Note that the winners’ Executive Summary section will be shared publicly. (approx. 0.75 pages)
• Plain Language Summary: Provide a summary of your submission that can be easily understood by a general audience. Capture the essence of your technical work in a manner that is accessible to those without specialized knowledge in the field. Think of it as explaining your work to someone without a technical background, ensuring that the main ideas and impacts are clear. This summary will be made public for winners and used for broader dissemination and to inform the public about the contributions and significance of your work. (approx. 0.5 pages)
• Challenge Area(s) Addressed: Select the specific challenge area your proposed solution targets either:Complex in vitro human-derived cell- or tissue-based modelsIn silico multi-scale systemsIn chemico cell-free systems, orIntegrated NAMs (with associated FAIR datasets and AI-engines, if applicable)
• Understanding of the Problem: Explain why a novel or improved NAM is needed, potential roadblocks, and solutions identified. (approx. 3 pages)
• Team Composition & Expertise: Provide details about your team, emphasizing interdisciplinary expertise. (approx. 0.75 pages)
• Approach for the Proposed NAM: Describe the technical specifications of the NAM in detail and discuss challenges that may arise in its development. Discuss how well the proposed NAM will predict outcomes in humans and describe the strategy to verify its predictive validity. (approx. 3 pages)
• Scientific Rationale: Provide a clear explanation, scientific rationale, and evidence base for your proposed solution. (approx. 1.5 pages)
• Novelty of the Idea: Highlight the novelty and innovation of your proposed idea. (approx. 3 pages)
• Potential Impact: Describe the potential impact of your idea on advancing the use of NAMs in the chosen challenge area. (approx. 3 pages)
• Multiple Submissions: Indicate if you will be submitting multiple solutions to cover multiple areas of the challenge. (Yes/No)

All submission content must be provided in English. Submissions must not include the HHS’ logo or official seal or the logo of NIH or any of its components and must not claim federal government endorsement.