Announcement of Requirements and Registration for the National Eye Institute 3-D Retina Organoid Challenge (3-D ROC 2020): Reduction to Practice
DATES AND DEADLINES
FOR FURTHER INFORMATION CONTACT
THE IC'S STATUTORY AUTHORITY TO CONDUCT THE CHALLENGE
SUBJECT OF THE CHALLENGE COMPETITION
RULES FOR PARTICIPATING IN THE CHALLENGE
REGISTRATION PROCESS FOR PARTICIPANTS
EVALUATION AND WINNER SELECTION
SUBMISSION INSTRUCTIONS AND TEMPLATE
The “3-D Retina Organoid'' Challenge 2020: Reduction to Practice (the “Challenge''), is an implementation prize competition in which the National Eye Institute (NEI), part of the National Institutes of Health, is asking for 3-D human retina culture systems with maximal relevance to human physiology and disease. Current retina culture models require over six months to develop and still do not capture the complexities of the human retina. The goal of the Challenge is to use innovative approaches to develop new in vitro 3-D human retina models that recapitulate the organization and function of the human retina and can be used to examine biology and disease processes. This challenge is a follow-on to the recent NEI 3-D Retina Organoid Ideation Challenge, and aims to invoke scientific and technological development of the model systems proposed during that ideation competition. Technological breakthroughs in this arena could allow researchers and physicians to better understand, diagnose, and treat retinal diseases.
Phase 1 submission period: September 4, 2018 – October 1, 2018*
Phase 1 judging period: October 2, 2018 to November 30, 2018
Phase 1 winners announced: December 2018
Phase 2 submission period: February 14, 2020 – March 2, 2020*
Phase 2 judging period: March 3, 2020 – April 30, 2020
Phase 2 winners announced: May 2020
*To be eligible to submit a solution for to each phase, the team lead must register through challenge.gov, specify the team members by uploading a list, and submit an abstract by one week from the first day of the open submission period. The abstract can be edited/revised and full solution can be added up to the last date of the phase 2 submission period. See more details under Registration Process for Participants (below).
The NIH may shorten the submission period for Phase 2 and adjust dates for judging and winner(s) announcement if the winners' submissions and feasibility assessments from the Phase 1 suggest shorter Phase 2 execution period is possible. The NIH will announce any changes to the timeline by amending the Announcement Notice on NEI’s 3-D ROC website and 3-D ROC’s page on challenge.gov.
THE IC'S STATUTORY AUTHORITY TO CONDUCT THE CHALLENGE
The general purpose of the NEI is to conduct and support research, training, health information dissemination, and other programs with respect to blinding eye diseases, visual disorders, mechanisms of visual function, preservation of sight, and the special health problems and requirements of the blind. The NEI is 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 will lead to innovative technology to accelerate vision research, generate new models for retinal diseases, and facilitate translation of basic research into better treatments.
SUBJECT OF THE CHALLENGE COMPETITION
Around the world, an estimated 285 million people are visually impaired; of these, 39 million are blind. In many cases, blindness and vision loss are the result of retina-damaging diseases that, if better understood, could be treated or have interventions applied to stop degeneration or provide protection to remaining viable cells. One limitation in furthering retinal research is that eye tissue is not readily available to study disease processes and test new therapies. However, retina biology researchers have developed methods to grow 3-D retina models in vitro from induced pluripotent stem cells (iPSC) and human embryonic stem cells (hESC). Current protocols vary in their strengths and limitations, but none can robustly recapitulate the complexity and functionality of the retina. In this Challenge, NEI seeks 3-D human retina organoid prototypes that are physiologically relevant. Such model systems could be transformational for vision research and regenerative medicine. New models could be used for applications such as understanding eye development, studying retinal biology, modeling diseases, identifying and testing treatments, and serving as a tissue source to use in transplantation. In this Challenge, solution(s) should yield reproducible, retina organoid models that represent the complexity, structure, and function of the human retina and are amenable for use in either modeling diseases or high-content screening (see Evaluation Criteria under Basis Upon Which Submissions Will Be Evaluated).
RULES FOR PARTICIPATING IN THE CHALLENGE
Solvers must be 18 years of age or older and may participate singly or as part of one or more teams. Team formation is encouraged and 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.
- 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 the 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;
- 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;
- 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, step-parent, child, or step-child).
- Federal grantees may not use Federal funds to develop their Submissions.
- Federal contractors may not use Federal funds from a contract to develop their Submissions or to fund efforts in support of their Submission.
- 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, 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 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.
- 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 federal, state, and local laws, regulations, and policies, including the NIH Guidelines for Human Stem Cell Research, NIH policy on human fetal tissue research described in Sec. 4.1.14 of the NIH Grants Policy Statement, the HHS Regulations for the Protection of Human Subjects (45 CFR 46), and the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules, as applicable. If human embryonic stem cells are used, only cell lines listed on the NIH Human Embryonic Stem Cell Registry are eligible for use. Appropriate biosafety practices should be employed; see Biosafety in Microbiological and Biomedical Laboratories as a reference manual.
- 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 Solver (or is an improved version of an existing work that the Solver 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 Solver is aware. In addition, each individual (whether participating singly or in a group) and each entity grants to the NIH an irrevocable, paid-up, royalty-free nonexclusive worldwide license to reproduce, publish, post, link to, share, and display publicly (e.g., on websites) the submission and abstracts on the web or elsewhere, and a nonexclusive, nontransferable, irrevocable, paid-up license to practice, or have practiced for or on its behalf, the solution throughout the world. Each participant will retain all other intellectual property rights in their submissions, as applicable. To participate in the Challenge, each Solver must warrant that there are no legal obstacles to providing the above-referenced nonexclusive licenses of Solver's rights to the federal government. To receive an award, Solvers will not be required to transfer their intellectual property rights to NIH, but Solvers must grant to the federal government the nonexclusive licenses recited herein.
- 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 participant’s full and unconditional agreement to abide by these rules. Winning is contingent upon fulfilling all requirements herein.
PARTNERSHIPS TO SUPPORT CHALLENGE SOLVERS
Consistent with the America COMPETES Act, as amended, NEI is partnering with private sector entities to support the prize competition. During the 3-D ROC 2020, resources for Solvers may be available by companies and organizations who have partnered with NEI to support the challenge. Partners will provide resources directly to Solvers upon request on an equitable basis. Resources may include: in-kind contributions (loaning of technology, early access to products, free consulting opportunity), discounts on products, services, or reagents, or in-kind or discounted consulting, among other resources. For a list of current partners and information on how to obtain resources, contact NEI3dROC@mail.nih.gov. All support offered by the partners to Solvers is provided on the partners’ own accord and resources, and not at the direction, involvement, or resources of NEI. NEI does not endorse the partners’ products, services, or enterprises.
Solvers may access the registration and submission platform in one of the following ways:
- Access www.challenge.gov and search for “NEI 3-D Retina Organoid Challenge 2020”
- Access the National Eye Institute’s 3-D Retina Organoid Challenge website (https://nei.nih.gov/3droc) and find the registration link.
To be eligible to submit a solution for to each phase, the team lead must register through challenge.gov, specify the team members by uploading a list, and submit an abstract by one week from the first day of the open submission period. The abstract can be edited/revised and full solution can be added up to the last date of the phase 2 submission period.
The total prize purse for this 2-Phase Challenge is up to $1,000,000. Up to 6 winners will be awarded up to $100,000 each at Phase 1. Phase 2 will have up to 3 winners and the prize purse will total $400,000 plus any Phase 1 prize money that was not awarded for Phase 1. Additional teams may be recognized with non-monetary awards. The NIH reserves the right to cancel, suspend, and/or modify this Challenge at any time by amending the Announcement Notice on NEI’s 3-D ROC website and 3-D ROC’s page on challenge.gov. In addition, the NIH reserves the right to not award any prizes if no solutions are deemed worthy. The Award Approving Official will be Francis S. Collins, M.D., Ph.D., Director of the National Institutes of Health.
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.
EVALUATION AND WINNER SELECTION
Basis upon Which Winner Will Be Selected. A panel of non-federal technical reviewers with expertise directly relevant to the Challenge will evaluate the solutions based on innovation and achievement of the scientific 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. Comments for each submission will be summarized and shared with the respective team leads.
Solutions will be evaluated for the extent to which data and other included information indicate that the organoid system meets the scientific evaluation criteria. The weights assigned to the evaluation criteria are guidelines from NEI to suggest which scientific goals are of emphasis and interest to the institute. This is a 2-Phase Challenge, meaning submissions addressing the scientific evaluation criteria can be submitted at either or both of the two deadlines. At each deadline, teams can submit a solution that includes data supporting the scientific evaluation criteria they have accomplished to date. Submission at Phase 1 is not required to submit solutions for Phase 2. Each Phase is associated with a unique evaluation period and possible prize purse. Only complete applications will be reviewed.
Instructions for submission: Please format submissions using the Application Template and submit to challenge.gov as a compiled PDF. If you plan to submit a solution, prepare and submit an abstract no later than one week after the submission period opens.
Detailed instructions on submission requirements and process can be found in the application template. Please note differences in page limits and requirements for Phase 1 and Phase 2 submissions. Phase 2 also requires a video abstract.
Basis Upon Which Submissions Will Be Evaluated.
Solutions must show publication-quality data demonstrating:
- A 3-D human retina organoid system that mimics the physiological and morphological features of the in vivo biology, consists of the major retina cell types (rod and cone photoreceptors, horizontal, bipolar, amacrine, and ganglion cells and Muller glia) with appropriate lamination and synaptic organization, and represents their biological functions and interplay. Components (neurons, retinal pigment epithelium [RPE], glia) may be produced separately or dissociated and recombined (1) if protocol is driven by a valuable biological question and (2) if in the process of re-assembly, specific functions/roles of cell types are delineated. Three-dimensional assembly may be achieved using various approaches, for example through self-organization that recapitulates natural development (“true organoid”) or through bioengineering with scaffolds, bioprinting, and/or microfluidic apparatuses.
- Retina organoids that are generated entirely from human cells (e.g. derived from iPSCs, hESCs, multipotent cells, or adult cells subjected to a combination of transdifferentiation/reprogramming methods).
- Modeling and treating retinal disease, or testing and developing drug (i.e., high content screening) therapies (for details, see Evaluation Criteria 4 below).
Explants are not of interest for this Challenge. Tissue-on-a-chip systems that use cells grown in 2-D co-culture and do not fully represent the structure, morphology, and function of the human retina are also not of interest. However, creative approaches that incorporate use of microfluidics or perfusion to enhance culture or extend duration of survival for 3-D organoid systems are acceptable.
Reviewers will be asked to use the following criteria when evaluating whether (in the form of results, graphs, images, etc.) a prototype 3-D human retina organoid meets evaluation criteria:
- Significant advances over currently available protocols in areas such as duration of culture, yield, and maturity/differentiation of all cell types in appropriate numbers and ratio.
- Potential impact on understanding the biology of the retina.
Evaluation Criterion 1. Impact and Innovation (20 points)
Solutions will be evaluated for creativity and originality of designs. An innovative approach may be novel, groundbreaking, or paradigm-shifting, or a creative application of existing approaches. For Phase 1 submissions, the approach should also be feasible; i.e., have a high likelihood to succeed in meeting or exceeding the scientific evaluation criteria NEI has defined. Overall, the solution should provide a novel solution to building a 3-D human retina that meets the desired scientific criteria (structure, function, morphology). Reviewers will be asked to specifically address:
- Impact on potential end users, clinical implications, and therapeutic advances —To what extent will the solution exert a sustained, powerful influence on the understanding of retinal diseases and accelerating research toward new therapies?
- To what extent does the solution address a significant barrier in the development of human retina organoids that are highly representative of human physiology? Does the approach speed up organoid development and differentiation time, improve yield, or increase production?
- How is the solution unique and does it improve upon state of the science for organoid technology?
- To what extent are novel concepts, approaches, methodologies, technologies or instrumentation used, or are existing approaches applied in a novel way?
- To what extent are cross-discipline techniques integrated to produce a 3-D human retina organoid prototype that addresses the scientific evaluation criteria? (applicable to Phase 1 only)
- Will the innovative solution and team executing it allow all scientific criteria to be met within the timeframe of the Challenge? Are any limitations to the approach discussed and addressed? (only applicable to Phase 1)
Evaluation Criterion 2. Cell Types, Structure, and Function (25 points)
Solutions will be evaluated for establishment of a human PSC-derived in vitro retina model system that resembles the morphology of a healthy-native retina and is viable through formation of photoreceptor outer segments and/or long-term survival of retinal ganglion cells with extension of axonal processes. Reviewers will be asked to address:
- Cell Types: How many neuronal (or neuronal derived) cell types are stably co-cultured (rod and cone photoreceptors, bipolar cells, ganglion cells, horizontal cells, and amacrine cells, Muller glia)? Are long-term viable and functional RPE, choroid or non-neuronal cell types (e.g., pericytes, microglia, astrocytes) incorporated? To what extent does the evidence presented show presence of cell types and 3-dimensional structure. If a cell type is lacking, is there justification for why it is not present and not needed for proof of principle (i.e. the disease being modeled lacks the specific cell type)?
- Structure: Are organoid prototypes 3-dimensional and properly oriented? To what extent do the synaptic layers recapitulate those of a laminated retina with multiple neuron classes present in numbers and proportions that represent an in vivo setting (as indicated by biomarkers of lineage and differentiation)? How many other retina and retina-relevant tissues, cells, or structures are included?
- Functional characterization of cell types: Are all cell types in the organoid (or added to the organoid) functional through the latest viable time point as shown by appropriate analyses, including electrophysiology (e.g., light response and recovery for subsequent responses, etc.), retinoid recycling, cell communication, functional connectivity, fluid transport in RPE, etc.?
Evaluation Criterion 3. Reproducibility, Quality Control, and Standardization (25 points)
Assessment of inter/intra-laboratory utility, transferability, and reproducibility, with conclusive evidence that organoid prototype is based on a reproducible protocol and the protocol produces a relatively standardized product.
- Reproducibility: To what extent do the data support reproducibility and standardization (e.g., data showing transferability to other labs and lack of variability from batch to batch) included? To what extent is documentation of standardization or commercialization highlighted (i.e. cGMP protocols or patent applications)? Are the methods (part of the Appendix) sufficiently detailed such that the efforts could be reproduced (e.g., Standard operating protocols)?
- Robustness: How do the data support advances in organoid development to decrease differentiation time, improve yield, or increase production?
- Have retina organoids been characterized to show they are free of microbial contamination and chromosomal defects (i.e. karyotyping, STR analysis, FISH analysis)?
- Are formal documented agreements with industry, or transferability to industry partners (MOUs, licensing, CRADA, in-kind or discounted validation) presented?
Evaluation Criterion 4. Endpoint Assay Specific Goals (30 points for EITHER category)
BIOLOGY/DISEASE MODELING (note: NEI is agnostic to which disease is chosen, as long as technology is developed to robustly recapitulate the disease):
- Does the organoid prototype demonstrate improvement in faithful biological complexity (e.g. macula, multiple cell subtypes present in physiologically similar ratios, etc.)?
- Does the model recapitulate some aspect of disease phenotype in one or more assays?
- Viability and scalability: If grown at one organoid/well, are 90% of organoids in a plate viable, as shown by random sampling in five wells across a dish? For how long are morphological and functional features maintained? Are methods that increase the production (e.g., many dozens) of organoids and/or allow the distribution of well-characterized organoids presented to enable multiple organoids to be compared in the same experiment?
- Is therapeutic intervention to treat the disease modelled with 3-D retina organoids (e.g. via gene editing, small molecules, cell replacement, etc.) demonstrated?
HIGH CONTENT SCREENING:
- Are retina organoid prototypes amenable to high content screening, which may include high content imaging, drug validation/toxicology, or functional genomic screening (e.g. does not include materials known to show strong compound adsorption)?
- Does the model recapitulate known retina toxicities based on morphological and functional readouts?
- Scalability and portability: Are organoids grown at medium throughput (e.g., in a 96-well plate) robust? When grown at one organoid/well, are 90% of wells in a plate viable, as shown by random sampling in five wells across a dish? For how long are morphological and functional features maintained? Are methods to mass-produce (e.g., 100s) organoids such that multiple plates can be compared in the same experiment included?