August 23, 2019- Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137
93.233, 93.837, 93.838, 93.839, 93.840, 93.279
This FOA invites applications for pre-clinical research to develop novel, mechanism-based pharmacotherapies to selectively reverse breathing suppression produced by opioids. Two critical phases of pre-clinical investigation are supported. Phase I: the identification and rigorous validation of candidate targets; Phase II: development of therapeutic candidates, such as small molecules, biologics, and natural products that modulate validated targets identified in Phase I, using relevant animal models or human cells/tissue. Specific Phase I and II milestones will be formalized pre andpost-award and will serve as a schedule of performance expectations to maximize the output from each phase of the study. Milestone performance will be a major, but not the onlyconsiderationin determining which applications will be selected to transition from Phase I to Phase II. Phase II extends up to addressing preclinical functional outcomes, toxicology, and pharmacokinetics needed to support an Investigational New Drug (IND) application. Multi-disciplinary, multiple PI teams combining expertise in respiratory neurobiology, opioid pharmacology and pre-clinical drug development are strongly encouraged. This FOA is intended for pharmacotherapeutic development. Projects proposing device and model development or validation, the elucidation of biological mechanisms, population-based epidemiology, or human subjects research would not be responsive. Reversal of the respiratory depression, without inducing generalized opioid withdrawal, or interfering with analgesic effects addresses the ultimate goal of developing better medical strategies for management of deleterious consequences of synthetic illicit, as well as prescription opioids.
January 24, 2020
30 days prior to the application due date
March 24, 2020
No late applications will be accepted for this Funding Opportunity Announcement.
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
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.
Conformance to all requirements (both in the Application Guide and the FOA) 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.
This FOA invites applications for pre-clinical research to develop novel, mechanism-based pharmacotherapies to selectively reverse breathing suppression produced by opioids. Two critical phases of pre-clinical investigation will be supported. Phase I: the identification and rigorous validation of candidate targets; Phase II: development of therapeutic candidates such as small molecules, biologics, and natural products that modulate validated targets in relevant animal models or human cells/tissues. It is anticipated that applications will include a research plan for both Phases I and II based on quantifiable metrics delineating key milestones in pharmacotherapy development. Phase II extends up to addressing preclinical functional outcomes, toxicology, and pharmacokinetics needed to support an Investigational New Drug (IND) application, and should include a product development plan appropriate to supporting an IND filing. This FOA targets that portion of therapeutic development between target validation and IND filing. Specific Phase I and II milestones will be formalized pre- and post-award and will serve as a schedule of performance expectations to maximize the output from each phase of study. Milestone performance will be a major, but not the only consideration factor in determining which applications will be selected to transition from Phase I to Phase II. Multi-disciplinary and multiple-PI teams with expertise in respiratory neurobiology, opioid mechanisms, and pre-clinical drug development are strongly encouraged. This FOA is intended for pharmacotherapeutic development. Projects proposing device and model development or validation, the elucidation of biological mechanisms, population-based epidemiology or human subjects research are not considered responsive to this FOA and will not be reviewed. (Examples of non-responsive topics are listed below.) .
Novel pharmacotherapies that selectively counteract opioid overdose-induced respiratory depression are urgently needed to address a dramatic increase in opioid related US deaths in recent years. Existing opioid receptor antagonists trigger acute withdrawal, interfere with analgesic properties, and may lead to renarcotization. Opioid antagonists are also insufficient to fully reverse respiratory depression produced by high-affinity, long-acting synthetic opioids requiring ventilation to be protected for extended periods and until the synthetic opioid is cleared. Respiratory depression is an unpredictable risk for millions of individuals using prescribed and/or illicit opioids and susceptible to overdose from recreational or medical use. Opioid-induced respiratory depression poses significant challenges for the management of patients with both chronic pain and compromised breathing conditions such as COPD, asthma, and sleep apnea. The development of pharmacotherapies, particularly alternatives to opioid receptor antagonists, to counteract opioid overdose and safeguard respiration are urgently needed to prevent opioid overdose deaths, and to enhance opioid-based strategies for pain management. Pharmacotherapies to stimulate respiration, without inducing generalized opioid withdrawal, or interfering with analgesic properties address the ultimate goal of developing better medical countermeasures for management of deleterious consequences of synthetic illicit, as well as prescription opioids.
Investigators interested in this FOA are strongly encouraged to contact scientific staff (see Section VI, Agency Contacts) to discuss proposed aims and FOA requirements well in advance of the application receipt date.
Landmark advances in understanding the development, organization, and homeostasis of ventilatory control mechanisms present immediate opportunities to move candidate targets (e.g. neurotransmitters and modulators, signaling pathways, receptors/ion channels, and molecular/genomic markers) into early pre-clinical testing for target validation (Phase I of this initiative) and therapeutic development (Phase II of this initiative). Selected examples of potential targets include (i.e., not limited to),
Target validation - Phase I (R61, 2-years)
The purpose of Phase I is to rigorously validate the best potential target(s) for development of novel therapeutics to counteract the respiratory depression effects triggered by opioid exposure/overdose. Target validation involves demonstrating that candidate neurotransmitters, modulators, receptors, ion channels, signaling pathways, genes, or other biological factors are directly coupled to mechanisms triggering respiratory rhythm and/or chemosensory responses pertinent to countering opioid effects on breathing. Modulation of specific target levels, using appropriate model systems and assays, should be used to provide proof of concept for the relevance of the proposed target(s) role(s) in ventilatory control, exhibit biological properties amenable to pharmacological regulation by small molecules, biologics, and/or natural products. For this program, target candidates should already have been identified based on previously conducted, mechanistic research (i.e. target discovery level research is not responsive). An array in vivo, in vitro, and computational approaches may be considered to validate respiratory and chemosensory targets. Potential strategies include but are not limited to cell lines (animal and/or human), in vivo assays or ex vivo tissue preparations of respiratory circuits, genomic technology (e.g. knockouts/mutants, siRNA), electrophysiology, optogenetic models, imaging, and chemical probes/pharmacology. The goal for Phase I is validation and selection of the most promising opioid induced breathing depression countermeasure target(s) to advance for therapeutic development in Phase II.
Examples of target validation research include, but are not limited to:
Examples of research that would not be responsivefor this program include:
Therapeutic product development - Phase II (R33, 3-years)
The purpose of Phase II is to accelerate pre-clinical development of novel therapeutic products (e.g. small molecules, biologics, natural products) to reverse opioid-induced breathing depression. Phase II will support research in the interval between target validation and product development sufficient to enable preparation of an IND application. Targets will be selected from those validated in Phase I of this proposal. Product development activities will include the pre-clinical pharmacology, safety, toxicology, chemistry, manufacturing and efficacy studies needed to identify a lead therapeutic(s) meeting the regulatory requirements to enter clinical investigation (i.e. IND filing). This FOA seeks applications that include a product development plan describing how the research will enable IND filing.
Research activities for therapeutic development include, but are not limited to:
Examples of research that would not be responsive for this program include:
Target validation/product development program
This program will be administered as phased (R61/R33) and milestone driven. As specified above, Phase I: (R61, 2-years) will support identification and rigorous validation of candidate targets, with pre-established quantifiable metrics (i.e. milestones) for evaluating and selecting candidate target(s) to transition to product development. Phase II (R33, 3-years) will support pre-clinical development of therapeutic candidates that modulate selected target(s) validated in Phase I. Quantifiable milestones for each selected target should include, but are not limited to specific benchmarks for moving product development from target selection to IND application enabling status, and critical go/no go decision points (i.e. decision tree) to determining when to continue or discontinue development of a particular target or product. Specific Phase I and II milestones will be formalized pre and post-award and will serve as a schedule of performance expectations to maximize the output from each phase of study. Milestone performance will be a major consideration in evaluating scientific progress, but will not guarantee approval to transition from Phase I to Phase II. In addition to performance metrics, an independent NIH committee with expertise in therapeutics development will evaluate the quality and strength of data included in progress reports, the feasibility of proposed Phase I targets for therapeutic development, and the potential of the selected products and product development plan to be IND application enabling. All proposed studies should lead toward US regulatory approval of a specific therapeutic product(s). This FOA is intended to support applications that provide a description and timeline of the specific studies proposed, noting that the cumulative data collected by the conclusion of the project may not be sufficient for an IND without additional research. However, the application should include a clear rationale for how the proposed research to be conducted will be IND enabling. This program will support up to 10 Phase I projects, with a maximum of 5 transitioning to Phase II. Therefore, not all projects will be approved for transition to Phase II. It is anticipated that grantees will meet for a one-day investigator meeting and a two-day HEAL PI meeting to discuss research progress and potential opportunities for collaboration , both to be held in Bethesda, MD.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
NHLBI intends to commit total costs of up to $7,000,000 in FY2020-2021 to fund up to 10Phase I (R61) awards.
NHLBI intends to commit total costs of up to $3,000,000 per year in FY2022-2024 to fund up to 5 Phase II (R33) awards.
Application budgets may request up to $450,000 direct costs to support Phase I activities and up to $385,000 direct costs per year in Phase II, up to 3 years. . Investigators are encouraged to request what is well-justified for their research program.
The maximum period of the combined R61 and R33 phasesis 5 years, with up to 2 years forthe R61phase and up to 3 years for the R33 phase. The scope of the proposed project should determine the requested project award period.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Non-domestic (non-U.S.) Entities (Foreign Institutions) 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 SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
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.
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 SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
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 FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
In particular, provide evidence ofthe respiratory neurobiology, opioid mechanisms, and pre-clinical drug development expertise of the Senior/Key Persons.
All instructions in the SF424 (R&R) Application Guide must be followed.
Application budget justifications should include plans for two annual investigator meetings in Bethesda, MD: (1) An annual one-day meeting for lead investigators of RFA-HL-20-031 funded projects to discuss research progress and potential opportunities for collaboration and (2) An annual 2-day HEAL Principal Investigators meeting.
Specific Aims: Describe the goals of target validation and therapeutic development for pharmacotherapeutics to selectively counteract opiate induced breathing depression.
Research Strategy: Provide a research plan for both Phase I (R61, target validation) and Phase II (R33, product development) of the proposed project. The research strategy must include a justification for the selection of target mechanism(s) and must describe how the target(s) are mechanism-based and clinically relevant to counteracting opiate induced respiratory depression. Discussthe desired (i.e. reversing opioid induced respiratory depression) and non-desired (i.e. blocking analgesia, triggering withdrawal) effects of the candidate target and product.
The application must include milestones the researchers expect to achieve by the end of the R61 phase (labeled as R61 Milestones), as well as milestones for the R33 phase (labeled as R33 Milestones). Milestones should be specific, measurable, results-focused, and time-bound metrics, and must identify critical go/no-go decision points (i.e. decision tree and timeline) identifying critical stages of target validation and product development. Include a Product Development Plan describing how the project will lead to an IND filing/application. It is understood that the proposed milestones for the R33 phase may be revised based on activities during the R61 phase.
The following modifications also apply:
All applications should use this section to address aPublic Access and Data Sharing Plan that, at a minimum, includes the following general elements:
Release of Publications
Sharing of Underlying Primary Data
Applicants are encouraged to review the entire NIH HEAL Public Access and Data Sharing Plan, https://heal.nih.gov/about/public-access-data, and include all information in the grant application needed to comply with the plan.
If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific to this FOA:
To what extent are the proposed pharmacotherapeutic targets mechanism-based, and clinically relevant to reverse opiate induced respiratory depression? To what extent is the proposed R61 Phase I likely to produce validated targets to move into R33 Phase II product development? How likely are the proposed Phase I (target validation) and Phase II (product development) research plans to be IND enabling?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Specific to this FOA:
To what extent is the goal of bringing together respiratory neurobiology, opioid mechanisms, and pre-clinical drug development expertise achieved, and is the combined expertise of study personnelwell aligned for pre-clinical pharmacotherapeutic target validation and IND enabling product development science?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
Specific to this FOA:
How well does the research plan address the desired (i.e. reversing opioid induced respiratory depression) and non-desired (i.e. blocking analgesia, triggering withdrawal) effects of the candidate target and product? How specific, measurable, and valid are the proposed milestones for evaluating scientific progress, determining feasibility of transitioning targets from Phase I to Phase II, and making go/no-go decisions at critical points of therapeutic development? How strong is the research and product development plan to enable development of an IND application?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
For research that involves human subjects but does not involve one of thecategories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHLBI, in accordance with NIH peer review policy and procedures, using the stated review criteria.
Applications will be assigned to the NHLBI. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Heart, Lung and Blood Advisory Council. The following will be considered in making funding decisions:
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.htmlor call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreementsare required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM)about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings.Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.
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Contact Center Telephone: 800-518-4726
HEAL Data Sharing and Open Access Policy
NIH intends to maximize the availability of publications and the sharing of underlying data for NIH-supported HEAL research projects. Under the Policy, applicants for extramural research funding (grants, cooperative agreements, and contracts) (collectively, "Applicants"), for HEAL research projects are required to submit a Public Access and Data Sharing Plan that (1) describes their proposed process for making resulting publications and to the extent possible, the underlying primary data immediately and broadly available to the public; or (2) if applicable, provides a justification to NIH if such sharing is not possible. Underlying Primary Data should be made as widely and freely available as possible while safeguarding the privacy of participants, and protecting confidential and proprietary data.
NIH understands the content of a Public Access and Data Sharing Plan will vary depending on certain factors including, for example, the size and complexity of the dataset. However, the Public Access and Data Sharing Plan should, at a minimum, address the following general elements:
1.Electronic copies of Publications will be deposited in PubMed Central with proper tagging of metadata to ensure online discoverability and accessibility within four weeks of acceptance by a journal. 2.Publications will be Published under the Creative Commons Attribution 4.0 Generic License (CC BY 4.0) or an equivalent license, or otherwise dedicated to the public domain (e.g., Creative Commons public domain tool, CC0).
3.Publications will be made publicly available immediately without any embargo period.
4.Underlying Primary Data for the Publications will be made broadly available through an appropriate data repository such as the HEAL central data repository.
5.To the extent feasible, Underlying Primary Data will be shared simultaneously with the Publication and made immediately accessible through release under the Creative Commons Attribution 4.0 Generic License (CC BY 4.0) or an equivalent license, or otherwise dedicated to the public domain (e.g., Creative Commons public domain tool, CC0).
6.To meet program goals under this initiative, NIH requires broad and responsible sharing of Underlying Primary Data from NIH-Supported HEAL Projects that protects and maintains the privacy and confidentiality of participant data. If the research involves human subjects, as defined by 45 C.F.R. 465, the Public Access and Data Sharing Plan should discuss how the privacy rights of participants and confidentiality of their data will be protected and maintained in accordance with 45 C.F.R. 46 and other applicable laws and regulations. ◦The Applicant shuld discuss the potential risks to research participants posed by data sharing and steps taken to address those risks, including the following: ◾Underlying Primary Data should be de-identified according to the standards set forth in the HHS Regulations for the Protection of Human Subjects to ensure that the identities of research subjects cannot be readily ascertained with the data.6 Underlying Primary Data should also be stripped of identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule.
7 Underlying Primary Data that are free of identifiers but contain sensitive information are immediately released with no fee for access but are deposited in controlled access repositories with similar policies to dbGaP (e.g., the controlled access repository should have an independent data access committee and no financial incentives for limiting access to datasets).Before submitting Underlying Primary Data, awardees through their Institutional Review Boards (IRBs), privacy boards, or equivalent bodies, will assess the informed consent materials to determine whether the Underlying Primary Data may be shared as contemplated in this Policy.
To meet program goals under this initiative, NIH requires broad sharing of Underlying Primary Data from NIH-Supported HEAL Projects but is responsive to concerns with protecting confidential and proprietary data, and consistent with other applicable laws and regulations. The Public Access and Data Sharing Plan should describe any anticipated confidentiality concerns and how they will be addressed in accordance with the requirements of the Policy and meeting the program goals of this initiative. For example, the data will be shared under licenses that retain intellectual property for commercialization but should also have features that promote broad and immediate access (e.g., no embargo and no fee for access) to meet program goals
Implementation of the Policy
The specifics of implementation of the Policy will depend on the mechanism through which the funding is being obligated or awarded. With respect to contracts involving a HEAL Project, a Public Access and Data Sharing Plan will be required to be submitted with contract proposals starting in fiscal year 2020 and will be incorporated as a contract deliverable. Review of the contract proposals will include an evaluation of the Public Access and Data Sharing Plan.
With respect to extramural HEAL funding for grants and cooperative agreements, starting in fiscal year 2019, NIH will give funding priority to those applicants that provide an appropriate Public Access and Data Sharing Plan that ensures maximal sharing of the Publications and Underlying Primary Data arising from the award. The Public Access and Data Sharing Plan will become a term and condition of the award, as detailed in the Notice of Award.
Applicants may include anticipated charges for publication or data sharing and resources that may be needed to support a proposed Public Access and Data Sharing Plan in the budget plan of their application/proposal. These charges may include but are not limited to article or author fees charged by open access journals, the Creative Commons or other equivalent copyright license fees, or similar fees.
Finally, NIH researchers engaged in intramural HEAL Projects that generate Publications or Underlying Primary Data will be required to comply with this Policy
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