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ASPIRE Design Challenge 2: Electronic Synthetic Chemistry Portal for Translational Innovation in Pain, Opioid Use Disorder and Overdose

Summary of NCATS ASPIRE Design Challenges

The 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).

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Summary of NCATS ASPIRE Design Challenge 2: Electronic Synthetic Chemistry Portal for Translational Innovation in Pain, Opioid Use Disorder and Overdose

Challenge 2 aims to address the need for 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). This Challenge requires submission of only a detailed description of the design of the eSCP, not the final working portal. The innovators may use currently available open source eLNs and modify them to meet the challenge’s requirements. While the focus of this Challenge is on a specific translational problem relevant to pain treatments and opioid use disorder and overdose, the eSCP should be designed to be generally applicable to any kind of laboratory chemical and biological data collection, recording and analysis of data relevant to any translational Challenge; modular; and well architected for advanced machine learning applications.

Evaluation criteria that reviewers will be asked to address are specified below.

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Dates and Deadlines

Solutions 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, 2019
Judging period: June 17, 2019-August 2, 2019
Winners announced: August 2019

For further information send an email to NCATSASPIREChallenge@mail.nih.gov

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The IC’s Statutory Authority to Conduct the Challenge 

The 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.

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Subject of the Challenge Competition

Challenge 2. Electronic Synthetic Chemistry Portal for Translational Innovation in Pain, Opioid Use Disorder and Overdose. In order to enable further access into the currently unexplored biological space relevant to treatment of pain and/or drug addiction and overdose, this second Challenge aims to reward and spur innovative solutions to the development next-generation, open source electronic laboratory notebook (eLN) that would serve as an electronic synthetic chemistry knowledge portal (eSCP) and allow for real-time molecular design hypothesis generation and unbiased data collection during the synthesis planning, execution and analysis while providing a strong and comprehensive contextual analysis to biological testing data of experimental targets and currently known pain drug comparators. This Challenge requires submission of only a detailed description of the design of the eSCP, not the final working portal. The innovators may use currently available open source eLNs and modify them to meet the Challenge’s requirements. The ultimate goal is to effectively utilize data and outcomes from both positive and negative synthetic chemistries for future discovery and development of novel structures and chemistries of relevance to the treatment of pain and opioid use disorder. The eSCP is expected to be modular or flexible to accommodate additional features if required and to provide an external control mechanism (e.g., API or CLI). All data entries, including chemical structures, should be in a format that can be easily ported to advanced machine learning algorithms and/or downstream analytical applications.

As described in A Quick Guide to ELN Regulatory Requirements, the developer of an eSCP system should be aware of and compliant with:

  • 21 CFR Part 11, the U.S. Food and Drug Administration (FDA) regulation of electronic signatures and systems
  • Good Laboratory Practices, particularly the GLP focus on traceability of data changes
  • Good Manufacturing Practices 2, specifically requirements for validation
  • PFSB 040122, the Japanese guideline
  • Annex 11, computer guidelines for the EU’s Good Manufacturing Practices
  • Potentially the guidelines of industry supplemental organizations:
    • International Standards Organization (ISO) 9001
    • Pharmaceutical Inspection Convention Scheme (PIC/S) Good Practices Guidance for Inspectors “Good Practices for Computerized Systems in Regulated ‘GxP’ Environments”
    • “The Application of the Principles of GLP to Computerized Systems” (OECD 1995)

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Concurrent Companion NCATS ASPIRE Design Challenges

NCATS 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 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.

Challenge 5: Integrated Solution for Translational Innovation in Pain, Opioid Use Disorder and Overdose rewards and spurs 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 Chemistry Database, Electronic Synthetic Chemistry Portal, Predictive Algorithms and Biological Assays, respectively) into a single platform.

Note: Each component of Challenge 5 (above) is also available as an individual Challenge at Challenge.gov.

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Registration Process for Innovators

Innovators may access the registration and submission platform in one of the following ways:

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The Prize

Amount 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.

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Evaluation and Winner Selection

Basis 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 Template

Instructions 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.

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Basis upon Which Submissions Will Be Evaluated

Challenge 2. Electronic Synthetic Chemistry Portal for Translational Innovation in Pain, Opioid Use Disorder and Overdose. In order to enable further access into the currently unexplored biological space relevant to treatment of pain and/or drug addiction and overdose, this second Challenge rewards and spurs solutions to the development of next-generation, open source electronic laboratory notebook (eLN) that would serve as an electronic synthetic chemistry knowledge portal (eSCP) and allow for real-time molecular design hypothesis generation and unbiased data collection during the synthesis planning, execution and analysis while providing a strong and comprehensive contextual analysis to biological testing data of experimental targets and currently known pain drug comparators. This Challenge requires submission of only a detailed description of the design of the eSCP, not the final working portal. The innovators may use currently available open source eLNs and modify them to meet the Challenge’s requirements. The ultimate goal is to effectively utilize data and outcomes from both positive and negative synthetic chemistries for future discovery and development of novel structures and chemistries of relevance to the treatment of pain and opioid use disorder. The eSCP is expected to be modular or flexible to accommodate additional features if required and to provide external control mechanism (e.g., API or CLI). All data entries, including chemical structures, should be in a format that can be easily ported to advanced machine learning algorithms and/or downstream analytical applications.

Judging criteria:

Evaluation Criterion 1: Impact and Innovation (20 points)

  • Did the team identify potential roadblocks and suggest additional expertise it would utilize to facilitate resolution of roadblocks to implementation?
  • To what extent is the proposal innovative — that is, to what extent does it involve a novel eSCP 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?
  • 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 platform 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?

Evaluation Criterion 2: Data Collection, Analysis and Integration (20 points)

  • How well does the eSCP parse 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., is it 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?

Evaluation 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 would 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 (e.g., tables, textboxes, formulas, etc.)?
  • Is the eSCP designed to be remotely accessible (e.g., off-site computers or mobile devices)?
  • Does the design of 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 (e.g., are dictionaries included)?

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Last updated on October 29, 2023