This FOA invites applications for human subjects research to elucidate sleep/circadian mechanisms closely-coupled to the risk of opiate use disorder (OUD), the pathobiology of opiate withdrawal, and the response to medication-assisted treatment (MAT). Identifying sleep/circadian mechanisms and determining the directionality of sleep and OUD interactions addresses a knowledge gap and new opportunities for improved therapy and outcome. Multi-disciplinary, multiple-investigator teams of researchers combining expertise in clinical research and mechanisms of sleep/circadian science and OUD/MAT are strongly encouraged. Clinical trials focused on mechanistic endpoints and/or understanding how an intervention works may be proposed. This FOA is only open to the study of OUD relevant mechanisms and pathobiology. The study of other drugs of abuse or efficacy focused trials will not be responsive.
December 10, 2018
No late applications will be accepted for this Funding Opportunity Announcement.
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.
This study is part of the of the 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.
Public Law 115-141, the Consolidated Appropriations Act of 2018 (signed March 23, 2018) includes a requirement that grantees from for-profit applicant organizations must provide a 50% match and/or in-kind contribution of all federally awarded dollars under the grant award (direct costs, as well as facilities and administrative costs) for research related to opioid addiction, development of opioid alternatives, pain management and addiction treatment.
Matching Requirement: A grantee from a for-profit organization funded under this funding opportunity announcement 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.The applicant will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applications must identify the source and amount of funds proposed to meet the matching requirement and how the value for in-kind contributions was determined. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award. NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement. See 45 CFR 75.306 for additional details.
This FOA invites clinical research applications to elucidate sleep and circadian mechanisms contributing to the risk of opiate use disorder (OUD), the pathobiology of opiate withdrawal, and that influence the response to medication-assisted treatment (MAT). Sleep and circadian biology are physiological regulators of neurobiological mechanisms ranging from synaptic plasticity and individual cellular processes to complex behaviors. The spectrum of mechanistic neurobiological knowledge associated with sleep and circadian biology needs to be juxtaposed with the neurobiology of OUD mechanisms and risk factors. Mechanistic studies to determine the directionality of sleep and OUD interactions in humans are needed to identify new opportunities for prevention and improved therapy. Multi-disciplinary, multiple-investigator teams combining expertise in clinical research, mechanisms of sleep and circadian rhythms, the neurobiology of OUD and neuropharmacology of MAT are strongly encouraged. This FOA is only open to the study of OUD relevant mechanisms and pathobiology. The study of other drugs of abuse will not be responsive. Evaluating the efficacy of one or more interventions without a rigorous mechanistic study design should not be proposed. The study of specific mechanistic interactions should be justified by an explicit explanation of the potential application to reducing OUD risk, improving MAT outcomes, and address the primary goals of the NIH Helping to End Addiction Long-term (HEAL) Initiative.
Opiate use disorder (OUD) afflicts over 2 million Americans and is a leading cause of accidental death, exceeding 20,000 cases in the US annually. OUD stems from the medical or recreational use of opioids that progresses into a cycle of misuse, addiction, withdrawal, relapse, and the most extreme consequence, overdose and death. Pharmacotherapies for OUD are available (e.g. methadone, buprenorphine, naltrexone), but relapse rates are high, leading to an intractable cycle of continued opiate abuse. Developing more effective strategies to prevent and manage OUD requires a more complete understanding of factors and neurobiological mechanisms driving susceptibility to OUD, the pathobiology of its trajectory, and the response to interventions, particularly medication assisted treatment (MAT).
Sleep deficiency including insufficient sleep duration, irregular circadian rhythms, and poor sleep quality, is prevalent in >75% of individuals with OUD. Studies are needed to discover how sleep deficiency , untreated sleep disorders, and altered circadian rhythms factor into the neurobiological and pharmacological substrate changes underlying addiction, physical dependence and withdrawal , including reward/reinforcement, risk taking behavior/mood regulation, autonomic regulation/integration, pain perception, and signaling in neuropharmacological pathways relevant to substance abuse. For example, sleep deprivation alters dopamine receptor expression and synaptic transmission in mesocorticolimbic brain regions, which may contribute to reward mechanisms and the trajectory of OUD. Sleep deficiency alters attention, emotion, and memory processes at the cellular level independent of physical manifestations such as sleepiness.
Neural regions mediating opiate withdrawal are also involved in sleep regulation (e.g. locus coeruleus, periaqueductal gray, and rostral ventromedial medulla), pointing to a potential mechanistic interface between the pathobiology of withdrawal and sleep. Time-of-day dependent variations in dopamine and opiate receptor expression, as well as, drug-craving, reward responses, and drug self-administration implicate circadian-coupled mechanisms. However, these relationships and the directionality of OUD interactions with sleep and circadian neurobiology are not well understood. Whether opiate-induced disruption of sleep and circadian rhythms exacerbates the neuropathology associated with the risk of OUD also needs study. Opioids disrupt the cyclical well-structured occurrence of sleep and the specific chemical, molecular, and anatomical signatures coupled to sleep stages but the relationship to OUD and efficacy of MAT remains to be elucidated. For instance, what is the significance of characteristic REM sleep neurochemical changes associated with activation of the emotion-coupled medial prefrontal cortex and subcortical regions (amygdala, striatum and hippocampus) in OUD and MAT? How do long-term effects of OUD on sleep and circadian regulation influence the trajectory of opioid use and opiate withdrawal during MAT? Studies are also needed to elucidate the mechanistic significance of specific of sedative-hypnotic agent categories used to manage comorbid insomnia during OUD and MAT. Delineating neurobiological and pharmacological mechanisms coupling sleep and OUD pathobiology will facilitate the identification of novel therapeutic targets for OUD prevention, management, and recovery of OUD.
This FOA will support mechanistic, human subjects research. Behavioral, pharmacological, genetic or other experimental models of sleep and circadian deficiency and OUD may be considered. An array of approaches, including in vivo, in vitro, genomic, imaging, pharmacologic, computational or other strategies may be proposed to study behavioral, physiological, molecular, genetic and pharmacological mechanisms coupling sleep and OUD.
Investigators may propose leveraging existing cohort studies (e.g. NIDA Clinical Trials Network, NICHD Maternal Fetal Medicine Units Network; NCATS and NINDS opiate/pain initiative programs) to facilitate participant recruitment with parent study concurrence. Study designs limited to the survey of populations , studies not involving human subjects, and studies limited to comparing the efficacy of one or more interventions without a rigorous mechanistic study design should not be proposed. Only NIH-defined clinical trials designed to elucidate mechanisms of action closely-coupled to well-recognized OUD/MAT outcomes will be supported. Projects developed for this program should contribute significantly to scientific objectives of the NIH HEAL (Helping to End Addiction Long-term) Initiative, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis.
Cooperative Agreement: This program will be administered as a cooperative agreement mechanism (U01). A description of the roles and responsibilities of awardee PIs/PDs, and NIH program officers and projects scientists is detailed in Section VI.2 of this FOA.
Specific Areas of Research interest include but are not limited to those listed below:
Scientific Knowledge to be Gained:
Countermeasures to prevent and treat OUD are urgently needed. Sleep deficiency and circadian abnormalities are prevalent characteristics of substance use disorders that may contribute to their development, maintenance and relapse. Elucidating key neurobiological mechanisms will reveal novel avenues for therapeutic developments to both reduce the risk of OUD and improve outcomes.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
The NHLBI intends to commit total costs up to $4,000,000 per year in fiscal years 2019 through 2022 to support up to 3 awards..
Application budget direct costs may not exceed $750,000 per year.
If the recipient is a for-profit institution, it is required to provide a matching of funds or documented in-kind contributions of not less than 50 percent of the total cost of Federal Funds awarded. There is no matching requirement for non-profits and Institutes of Higher Education that receive these funds. For-profit subrecipients and vendors are not subject to the matching requirements.
The maximum project period is 4 years.
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
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.
For grantees from a for-profit organization, this FOA does require cost sharing, as defined in the NIH Grants Policy Statement. More information on cost matching requirements is in Section IV.2 R&R or Modular Budget
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
Buttons to access the online ASSIST system or to download application forms 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.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
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
Division of Extramural Research Activities
National Heart, Long, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
All instructions in the SF424 (R&R) Application Guide must be followed.
Applicant budget justifications should include plans for an annual, one-day coordination meetings (Bethesda, MD) among lead investigators to identify opportunities for collaboration and to coordinate presentations at national meetings.
Cost Matching Requirement for For-profit Applicants
Cost matching or documented in-kind contributions is required for for-profit organizations responding to this FOA. The for-profit awardee is required to match funds or provide at least a 50% matching of funds or documented in-kind contributions at a rate of not less than 50% of the for the total-Federally awarded amount (direct costs, as well as facilities and administrative costs), as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.
Federal funds may not be used as a source of matching funds. Generally, cost matching requirements may not be met from the following sources:
a) Costs borne by another Federal grant or sub award;
b) Costs or contributions toward cost sharing on another Federal grant, a Federal procurement contract, or any other award of Federal funds;
c) Cost of services or property financed by income earned by contractors under a contract from the recipient (or sub recipient);
(d) Program income; and
(e) Patient incentives.
The for-profit organization will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applicants must submit budgets that clearly document the total costs, the source and amount of matching funds, and how valuation was determined in the case of in-kind contributions, as well as the Federal and Institutional (non-Federal) components of the budget. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award. NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement. See 45 CFR 75.306 for additional details.
Budget Justification: All for-profit applicants must document the matching (non-Federal) component and the federal (non-matching) component in the total project budget. That is, the requested budget plus the cost-matching budget must be detailed in tabular format to document the cost-matching (non-Federal) component and the federal (non-cost matching) component. The amount of matching is subject to adjustment based on total allowable costs incurred. All costs and contributions used to satisfy the matching requirement must be documented by the recipient, including how the value for in-kind contributions was determined, and are subject to audit. The cost matching requirement is not negotiable for for-profit organizations.
Specific Aims: Clearly describe the scientific question/hypothesis under investigation and how the proposed mechanism(s) under study will be relevant to advancing the understanding of sleep/circadian and OUD/MAT interactions.
Research Strategy: Clearly describe how the proposed research/intervention design will contribute significantly to elucidating the mechanisms and directionality of sleep/circadian and OUD/MAT interactions. For studies meeting the NIH definition of a clinical trial, clearly specify the mechanistic endpoints that will be evaluated. Note: This FOA will not support efficacy-focused trials.
Letters of SupportFor-profit applicants must include a letter(s) of support confirming that the required secured cost matching (cash; in-kind commitments such as salary, consultant costs, equipment) is available and confirm that the essential personnel have the authority within the organization to allocate resources.
The following modifications also apply:
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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
In addition, for applications involving clinical trials:
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
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?
In addition, for applications involving clinical trials
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
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?
In addition, for applications involving clinical trials
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
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?
In addition, for applications involving clinical trials
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
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?
In addition, for applications involving clinical trials
Does the application adequately address the following, if applicable
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
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?
In addition, for applications involving clinical trials
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
For research that involves human subjects but does not involve one of the categories 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 six 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.
Individuals Across the Lifespan
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.
Specific to this FOA:
How likely is it that the plans for cost matching will be adequate?
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.
Special award condition specific to this FOA: A grantee from a for-profit organization funded under this announcement 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. See 45 CFR 75.306 for additional details. Matching funds must be non-Federal funds set aside for this project and are available from the source(s) identified in the application, as committed to by the recipient. Cost matching will be evaluated by the awarding office to ensure that this requirement is being met. Compliance with the matching requirement must be verified on an annual basis and must be documented in the annual and final FFR.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all 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. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
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.html; and https://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.html or 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 following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations 45 CFR 75, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NHLBI Project Officer (PO) as defined below.
The PI(s)/PD(s) will have primary responsibility for:
Providing effective leadership and management of research projects.
Developing and defining study approach, plans, conduct and analysis.
Meeting goals, timelines, and milestones of approved studies.
Collaborating with NHLBI Program Officer (PO) and NHLBI and NIDA Project Scientists (PS) in all aspects of scientific and technical research needed for the management of the study.
Participation on a Steering Committee comprised of project PIs and NIH project scientists.
Agreeing to abide by the recommendations and reporting requirements made by an NHLBI appointed Data and Safety Monitoring Board (DSMB).
Ensuring participation by their site in SC and DSMB meetings.
Attendance in all required annual PI meetings and teleconferences. Note: The PD(s)/PI(s) should plan for at least one in person meeting in the Washington DC Metro area annually.
It is expected that public dissemination of results, tools, protocols, resources and other products will be accomplished in a timely manner, in accordance with NIH data and resource sharing policies.
NHLBI staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards as described below:
NHLBI staff will interact with the PD(s)/PI(s) on a regular basis to monitor progress and negotiate goals. Monitoring may include: regular communication with the PI and his staff, site visits for discussion with awardees’ research team, evaluation of enrollment targets, QA/QC of human subjects safety/protection, fiscal reviews, and other relevant stewardship matters.
For each award there will be a NHLBI PO and a member of NHLBI staff responsible for the normal scientific and programmatic stewardship of the award. The PO will be named in the award notice. The NHLBI will also retain its typical stewardship role. addition, there will be an NHLBI and NIDA PS assigned to the award. The PS will have substantial and programmatic involvement during the conduct of this activity. The PS will have primary responsibility for:
Serving as a resource to provide scientific/programmatic support during the accomplishment of the implementation study by participating in the design of the activities, advising in the selection of sources or resources, advising in management and technical performance, or participating in the preparation of publications.
Assisting in the development and modification of study protocols.
Providing assistance, coordination and facilitating interactions and collaborations between the individual projects funded under this program.
The NIH reserves the right to phase out or curtail the award (or an individual component of the award) in the event of inadequate progress or data reporting. NHLBI support of this study is contingent upon adequate participant recruitment based on the Recipient's Milestone Accrual Plan submitted at the time of funding. The Recipient is expected to demonstrate best effort compliance in accordance with the NHLBI Milestone Accrual Policy ( http://www.nhlbi.nih.gov/studies/index.htm ). Failure to achieve minimally acceptable milestone recruitment levels may result in the withholding of future support and or negotiating an orderly close-out of this study.
Areas of Joint Responsibility include:
A Steering Committee (SC) will be formed to identify potential areas of scientific synergy (e.g. uniform procedures, measures, policies) between the awarded projects, and for ongoing discussion of scientific progress, barriers, dissemination of results, or other topics related to project performance. The SC membership will include the NHLBI PS and the PD(s)/PI(s) of each award. The SC Chair will not be an NHLBI staff member but will be appointed by NHLBI. Additional members may be added by action of the SC. Other government staff may attend the SC meetings, if their expertise is required for specific discussions. The SC will schedule quarterly conference calls, at minimum. Each contact PD/PI and the NIH PS will have one vote , in cases where decisions need to be made; the Chair will have one vote in case of a tie.
An independent Data and Safety Monitoring Board (DSMB) will be appointed by NHLBI to provide overall monitoring of study protocols, performance and participant safety issues. An NHBLI scientist, other than the PS will serve as Executive Secretary to the DSMB.
Dispute Resolution :
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The three members will be: a designee of the SC chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
A final Research Performance Progress Report (F-RPPR), invention statement, and the expenditure data portion of the Federal Financial Report, including Federal and non-Federal share for cost matching, are required for closeout of an award, as described in the NIH Grants Policy Statement.
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 agreements are 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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Steve Grant, PhD
National Institute on Drug Abuse (NIDA)
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