Catalyze: Enabling Technologies and Transformative Platforms for HLBS Research (R33)

Catalyze: Enabling Technologies and Transformative Platforms for HLBS Research (R33) is sponsored by US Department of Health & Human Services: National Institutes of Health (NIH). Aims to support the development of enabling technologies and transformative platforms for heart, lung, blood, and sleep research.

RFA-HL-26-016: Catalyze: Enabling Technologies and Transformative Platforms for HLBS Research (R33 - Clinical Trials Not Allowed) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Heart, Lung, and Blood Institute ( NHLBI ) Funding Opportunity Title Catalyze: Enabling Technologies and Transformative Platforms for HLBS Research (R33 - Clinical Trials Not Allowed) R33 Exploratory/Developmental Grants Phase II.

January 28, 2026 - NIH Removing AIDS Application Due Dates from NOFOs. See Notice NOT-OD-26-029 . March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II Exploratory/Developmental Grants Phase II Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II Exploratory/Developmental Grants Phase II See Section III. 3.

Additional Information on Eligibility. Assistance Listing Number(s) 93. 837, 93.

838, 93. 839, 93. 233 Funding Opportunity Purpose This Notice of Funding Opportunity (NOFO) solicits grant applications to further develop enabling technologies and transformative platforms to catalyze next-generation predictive, diagnostic and therapeutic products to address heart, lung, blood, and sleep (HLBS)-related disorders and diseases.

This NOFO solicits R33 applications where major feasibility gaps for the enabling technology or transformative platform have already been overcome, as demonstrated with supportive preliminary data, but still requires further development and rigorous validation to encourage downstream demonstration, utilization and adoption.

Well-suited applications must offer the potential to accelerate and/or transform the areas of early detection and screening, model development, clinical diagnosis, treatment, control, prevention or epidemiology, while addressing issues associated with HLBS-related diseases and disorders.

Projects proposing application of existing technologies where the novelty resides in the biological or clinical target/question being pursued are not appropriate for this solicitation. Applications considered nonresponsive to the NOFO will not be reviewed.

This NOFO is part of a suite of Catalyze innovation grants to advance projects to the point where they can meet the entry criteria for the NHLBI Catalyze Product Definition or Preclinical NOFOs.

Funding Opportunity Goal(s) To foster heart and vascular research in the basic, translational, clinical and population sciences, and to foster training to build talented young investigators in these areas, funded through competitive research training grants. The Division of Lung Diseases supports research and research training on the causes, diagnosis, prevention, and treatment of lung diseases and sleep disorders.

Research is funded through investigator-initiated and Institute-initiated grant programs and through contract programs in areas including asthma, bronchopulmonary dysplasia, chronic obstructive pulmonary disease, cystic fibrosis, respiratory neurobiology, sleep and circadian biology, sleep-disordered breathing, critical care and acute lung injury, developmental biology and pediatric pulmonary diseases, immunologic and fibrotic pulmonary disease, rare lung disorders, pulmonary vascular disease, and pulmonary complications of AIDS and tuberculosis.

The Division is responsible for monitoring the latest research developments in the extramural scientific community as well as identifying research gaps and needs, obtaining advice from experts in the field, and implementing programs to address new opportunities.

The Division of Blood Diseases and Resources supports research and research training on the pathophysiology, diagnosis, treatment, and prevention of non-malignant blood diseases, including anemias, sickle cell disease, thalassemia; leukocyte biology, pre-malignant processes such as myelodysplasia and myeloproliferative disorders; hemophilia and other abnormalities of hemostasis and thrombosis; and immune dysfunction.

Funding encompasses a broad spectrum of hematologic inquiry, ranging from stem cell biology to medical management of blood diseases and to assuring the adequacy and safety of the nation's blood supply. Programs also support the development of novel cell-based therapies to bring the expertise of transfusion medicine and stem cell technology to the repair and regeneration of human tissues and organs.

The National Center on Sleep Disorders Research (NCSDR) supports research and research training related to sleep disordered breathing, and the fundamental functions of sleep and circadian rhythms.

The center also stewards several forums that facilitate the coordination of sleep research across NIH, other federal agencies and outside organizations, including the Sleep Disorders Research Advisory Board and an NIH-wide Sleep Research Coordinating Committee. The center also participates in the translation of new sleep research findings for dissemination to health care professionals and the public.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Catalyze: Enabling Technologies and Transformative Platforms for HLBS Research The NHLBI Catalyze innovation program is designed to provide a suite of comprehensive support and services to facilitate the transition of basic science discoveries into new treatments for diseases and disorders that fall under the NHLBI mission.

The Catalyze Program initiatives support product development (supporting product definition studies and pre-clinical research and development) and enabling technologies and transformative platforms.

Catalyze is coordinated by the Catalyze Coordinating Center, which provides program administration and evaluation, milestone-driven project management, communications and outreach, as well as development guidance for projects in the Catalyze portfolio. The Catalyze program aims to create cultural and systemic changes to more rapidly move breakthrough innovations to products that will have health, economic, and societal impact.

Information on the Catalyze programs can be found on the Catalyze website This specific Catalyze Notice of Funding Opportunity (NOFO) solicits grant applications to rigorously validate transformative, multi-use platforms or technologies that can enable the next generation of predictive, diagnostic and therapeutic products or model systems relevant to heart, lung, blood and/or sleep (HLBS)-related diseases or disorders.

Well-suited applications must offer the potential to significantly accelerate and/or transform the areas of early detection and screening, model development, clinical diagnosis, treatment, control, behavior, prevention or epidemiology. Proposed platforms and technologies may have widespread applicability but must be able to improve the outlook for HLBS-related diseases and disorders.

NOFO Emphasis: The NOFO is suitable for projects in which major feasibility gaps for the technology or platform have already been overcome, as demonstrated with supportive preliminary data, but still requires further development and rigorous validation to establish repeatable, reliable performance in an HLBS-relevant context. Recipients projects should be between a mid- stage Technology Readiness Level (TRL) 3 and TRL4.

For more information about technical readiness please refer to the Technology Readiness Guidelines. Projects where the novelty resides in the application of the technology to a single biological issue or clinical need, or involves an efficacy demonstration for a specific disease or condition, are not appropriate for this NOFO. Applications considered nonresponsive to this NOFO will not be reviewed.

However, such applications may be appropriate for other Catalyze NOFOs. The proposed projects must be focused on development and validation of an enabling or platform technology in a representative biologically or clinically relevant system.

In addition, all projects proposed in response to this NOFO must involve the following general attributes: Offers novel capabilities that may be judged by appropriate experts as potentially transformative in laboratory and/or clinical settings, and beyond providing incremental improvements to existing capabilities.

Rigorous study design with a verifiable approach, based on well-defined, performance measures (see below for description of performance measures). An application lacking performance measures will not be reviewed. For details on addressing these requirements, see Section IV.

Application and Submission Information . Responsive Technologies and Scientific Scope Responsive technologies include relevant novel or hybrid materials, chemical reagents, instrumentation, devices, and associated methods and models.

These technologies may be intended for molecular, cellular and/or organ-level analyses in-vitro , in-situ, and/or in-vivo (with some exceptions listed below), and may target basic, diagnostic, translational, epidemiological, and/or clinical gaps.

It must be clear that proposed projects are focused on the development of platforms and technologies to enable development in certain areas ( e.g. ,clinical detection, drug development, biomarker discovery and validation, or epidemiology), and NOT on pursuing specific discoveries ( e.g. , discovery of a novel biomarker or demonstrating efficacy for a novel therapeutic agent) or specific applications ( e. g .

detection of a known biomarker) in those areas. Technology development projects that are HLBS-relevant are encouraged provided that the technology proposed meets the requirements stated above, including transformative potential. Technologies may target atomic, molecular, sub-cellular, cellular and/or organ-level features.

At the core of any project must be a novel analysis or targeting capability (encompassing novel devices, materials, or chemical/biochemical approaches) with an accompanying validation plan.

General areas of interest include, but are not limited to, the following: Drug discovery platforms for identification of molecules that stimulate endogenous repair mechanisms In vitro and in vivo models that enable clinically-relevant safety and efficacy testing of therapeutics Gene delivery and gene therapy technologies that minimize cost-of-goods and maximize safety (including reduced risk of insertional mutagenesis and ability to control expression levels and/or killing of cells with inappropriate expression) Technologies, including materials and devices, to deliver pharmaceutical or cell-based therapeutics Technologies for non-invasive, clinically relevant diagnosis and monitoring Cell expansion technologies that maintain adult stem cell self-renewal without concomitant increases in risk of transformation Tools to discover clinically-relevant biomarkers Novel tools or approaches for producing and improving animal models Technologies that can facilitate and/or enhance molecular analyses in HLBS disease epidemiology (e.g., by allowing for rigorous and/or expeditious collection of various relevant types of data) Point-of-care technologies (POCTs) to facilitate the collection of relevant biological data for examining the factors contributing to health disparities (e.g., for HLBS disease sub-types and differences across individuals with a variety of backgrounds) New approaches for stem cell authentication and standards Strategies for tracking and monitoring of stem cell therapies in vivo IMPORTANT NOTE: Researchers uncertain as to whether their intended technology development project meets the requirements of this NOFO are encouraged to contact the Scientific/Research Contact(s) listed in Section VII .

Applications considered non-responsive to the NOFO will not be reviewed. Focus on the following will be considered non-responsive: Biomarker discovery or biomarker validation.

Pursuit of a biological or clinical hypothesis for which the novelty of the project resides in the biological or clinical question ( i.e. , traditional biological hypothesis-driven research) and NOT in the novel technical capability being developed; Development of specific contrast agents (though generalizable contrast agents are allowed); Development of drugs or therapies only intended to treat a specific disease or condition Development of devices only intended to treat a specific disease or condition Projects focused primarily on software/informatics solutions, database development, data mining, statistical tools, and computational/mathematical modeling (including those applicable to drug and/or patient responses) with the exception of projects which include software development for embedding in new devices or limited amounts of computational efforts as might be needed to develop new devices or methods.

Projects which are earlier in development, without first-generation prototypes and/or where major feasibility gaps for the enabling technology or transformative platform have not already been overcome are not responsive to this announcement, but should consider applying for support under NOT-HL-21-024 "Notice of Special Interest (NOSI): Bold New Bioengineering Research for Heart, Lung, Blood and Sleep Disorders and Diseases (Reissue)" and its reissues.

Projects which are later in development, that have already developed a prototype of an enabling technology or transformative platform of proven feasibility, that has also satisfied rigorous performance measures, should consider applying for support from the Catalyze Product Definition NOFOs listed on the NHLBI Catalyze website Special Requirements for this NOFO Each project is expected to use project management processes that guide the studies to successful completion of the established milestones.

While it may not be possible to have a full-time project manager, each project is expected to identify a team member who will hold this responsibility as a part of their project management plan. The Catalyze Coordinating Center may support the local project management through resources, educational materials, and regular communications.

The project manager will support the development of milestones, timelines, and identification of risks and mitigation strategies and will work closely with the Program Officer and with the support of the Catalyze Coordinating Center to update and refine these upon notice of award and as needed through the project.

Applicants are expected to propose activities and milestones, with an associated timeline, to be completed during the proposed duration of award. Recipients will develop specific, measurable, achievable, relevant, and time-bound Specific Aims for their project. Specific Aims or a list of activities planned for each year are not considered milestones because they do not provide decision-making goals.

Each Specific Aim should have at least one milestone associated with it. Milestones are an event or moment in time in a project that indicate progress toward a Specific Aim or a Specific Aim has been met. The project Specific Aims and milestones should be laid out as a timeline or GANNT chart as a part of the application.

Milestones will be peer reviewed as well as programmatically reviewed and if needed will be negotiated with the recipient before they are included in the terms of the award. NHLBI staff will monitor program progress against proposed milestones through quarterly meetings and make non-competing award decisions annually based on achieving milestones.

NHLBI emphasizes the importance of the robustness and reproducibility of experimental results in evaluating progress. Additional Considerations Applicants are strongly encouraged to contact Scientific/Research Staff listed in Section VII to discuss potential research projects prior to submitting an application.

Prior to funding an application, NHLBI Program staff may contact the applicant to discuss the proposed performance measures, milestones, and any changes suggested by the NHLBI review panel or Program staff. A final set of approved performance measures and milestones will be specified in the Notice of Award. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO. Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards NHLBI intends to commit total costs of up to $2,156,000 in FY 2026, $2,156,000 in FY 2027, and $2,156,000 in FY 2028. NHLBI expects to fund up to 4 new awards in FY 2026, 4 new awards in FY 2027, and 4 new awards in FY 2028, for a total of up to 12 new awards.

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets must not exceed $350,000 direct costs per year. The total budget must reflect the actual needs of the proposed project and annual project budgets must reflect the actual costs anticipated in each year.

The maximum project period is two years. The scope of the project should determine the project period. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed.

Statement of Potential Impact (Required) The filename "Statement of Potential Impact. pdf" should be used. The attachment may not exceed one page.

Provide a description of the expected potential of the proposed technology to transform HLBS-research and clinical practice.

Address the following questions: How is the new capability provided by the proposed technology potentially transformative and why may it be expected to produce an unusually high impact on biomedical research and medicine (i.e., describe the potentially transformative outcomes that might be realized should this technology be successfully developed)?

If applicable, how will the proposed technology overcome limitations for currently available technologies or alternative approaches (i.e., provide evidence to substantiate the claim of innovativeness beyond currently available technologies)? What are the next steps for the transformative capabilities to be transferred and/or demonstrated in a prototype product?

Is there a track-record of such development, or are partnerships and collaborations in place? SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed.

Applicants should include budget support for the PD/PI to participate in a 1. 5-day NHLBI-held innovation meeting or workshop once each budget year in the Washington, DC/Metropolitan area. Applicants should budget for an appropriate amount of project management support.

All instructions in the How to Apply-Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Research Strategy: Applicants must address all of the following required aspects: Advanced Development and Validation of HLBS-relevant Technology.

Applications must focus on further development of a novel technology beyond the early-stage proof of concept demonstration and engage a rigorous validation of the novel capability in an HLBS-relevant biological context of use that targets the needs of basic, preventative, diagnostic, translational, epidemiological, and/or clinical research.

Applications must provide appropriate background/preliminary data to justify that the proposed technology has passed the pilot developmental stage and shows promise. Describe the strategy and specific research steps to evaluate and rigorously validate the proposed technology within the context of its intended use (see performance measures, below). Substantial Improvement and/or New Capabilities.

All proposed technologies must offer the potential for substantial improvements over conventional approaches and/or add qualitatively new research capabilities not provided by existing technologies and approaches. Transformative Potential. Define clearly the unmet technical need from the community being targeted by the technology and describe its anticipated use in laboratory research and/or clinical settings.

Claimed potential impact is expected to be substantiated by specific performance measures (next bullet). Performance measures. Propose explicit performance measures that are objectively assessable measures for determining targeted performance capabilities.

They should be carefully justified and selected, and precisely defined, and must clearly detail the expected advantages of the proposed technology relative to existing technologies/approaches.

Appropriately targeted performance measures require that the underlying experimental results have been subjected to appropriate statistical analysis, yielding a reasonable level of certainty that the targeted level of performance has been achieved. Milestones : Define milestones that are specific, measurable, achievable, relevant, and time-bound.

The milestones should allow program staff to assess progress during the period of the award. Specific aims or a list of activities are not considered milestones. Describe the milestones that need to be reached in the R33 phase to address the specific aims and ensure the successful completion of the entire project.

Timeline :Provide a detailed timeline with specific milestones for the work proposed in each year of the award. The timeline, specific goals and feasibility milestones should be clear and complete. Indicate when it is anticipated that essential components of the project will be completed.

The proposed timeline with specific milestones should be clearly delineated and should be referenced in the Research Strategy Section. Project Management: Describe specific plans for utilizing project management processes to enable continuous assessment of the progress of the project relative to the established milestones and how the progress assessments will be used to make strategic decisions regarding the proposed project.

While it may not be possible to have a full-time project manager, each project is expected to identify a team member who will hold this responsibility as a part of their project management plan. The Catalyze Coordinating Center may support the local project management through resources, educational materials, and regular communications.

Rigor and Reproducibility High-quality and reproducible product definition studies are an essential cornerstone of the translational research enterprise. Attention to principles of study design and transparency is essential to enable stakeholders to assess the quality of the experimental design and scientific findings.

In support of this important goal, investigators must follow instructions to address Rigor and Reproducibility (https://grants. nih. gov/policy/reproducibility/index.

htm). Additional Information on Performance Measures Within Research Strategy there must be a dedicated subsection labeled "Performance Measures". Performance measures should be well-described, quantifiable, and scientifically justified.

Critical components for proposed measures include the numerically described target of performance as well as the means by which it will be assessed. Proposed performance measures will be a means of supporting success for the validation of the technology. Performance measures should include the relevant statistical context for the targeted parameter.

Whenever appropriate, present the proposed measures in the context of current technologies to substantiate the anticipated transformative potential. All performance measures should be described within the context in which they would be assessed, statistical strength of the resulting measures, and the approach by which they will be determined. Specific aims may not be regarded as performance measures.

The specific aims describe the goals and intended path of the research. Performance measures provide the means for objectively assessing progress against those aims and substantiate the potential impact the technology might have on HLBS research or clinical use. The project will be evaluated for success based on the completion of the performance measure(s) proposed.

For some specific aims, it may be sufficient to define a single performance measure. For others, multiple performance measures may be more appropriate. An example of a properly described performance measure could be achieving a detection limit of 1 femtogram of a targeted analyte per microliter of sample or less with a p value < 0.

05 under conditions a , b and c , and with 95% confidence limits +/- 0. 2 fg for a 2 fg reading over a concentration range of g to h . Other types of performance measures might include: Detection of a single mutated cell out of 109 differentiated therapeutic cells, with false positive detection rate <2%; Demonstration that the measured analyte is highly correlated (Pearson correlation coefficient r >0.

95) for a given human serum sample when analyzed on different days.

This should include mean, standard deviation, and relative standard deviation for repeatability targets superior to next best approach (if applicable); Reduction of sequence read errors to one in 5,000,000 base pairs; and/or Demonstration that the technology can be n-fold faster, or n-fold more sensitive, or n-fold more specific, etc, than the current "gold standard" technology.

Please note these additional performance measure examples should still be properly described in an experimental