Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). 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.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

According to the 2013 National Survey on Drug Use and Health, an estimated 24.6 million Americans aged 12 or older used illicit drugs in the past month and 21.6 million were classified with a substance use disorder (SUD). Marijuana was the most commonly used illicit drug, with 19.8 million past-month users. Marijuana was the illicit drug with the largest number of persons with past year dependence or abuse in 2013, followed by pain relievers, then by cocaine. The same survey estimates that of the 6.9 million persons with an illicit drug use disorder, 4.2 million had marijuana, 1.9 million pain reliever, 855,000 cocaine, and 517,000 heroin use disorder. These results show that SUDs are a significant public health problem that needs immediate attention.

Currently, there are medications approved by the Food and Drug Administration (FDA) for the treatment of nicotine and opiate dependence. However, none of these medications provides optimal therapy. There are no FDA approved medications for cocaine, methamphetamine, or cannabis use disorders. Thus, the development of safe and effective medications to treat these disorders is an urgent public health need.

Scientific advances are offering extraordinary opportunities for the development of medications to treat SUDs. These advances include the discovery of genes and proteins, receptors, neurotransmitters, neuromodulators, and brain circuits associated with drug abuse, as well as risk and protective factors for the onset and progression of these disorders. Multiple therapeutic approaches, ranging from small molecules to biologics (e.g., vaccines) may be poised for the next step in the FDA approval process, and concerted efforts are needed to advance these potential pharmacotherapies to approval.

The purpose of this award is to support outstanding basic and/or clinical researchers with the vision and expertise to translate research discoveries into medications for the treatment of Substance Use Disorders (SUDs) stemming from tobacco, cannabis, cocaine, methamphetamine, heroin, or prescription opiate use. Eligible applicants must demonstrate the ability to develop molecules with the potential to treat SUDs and advance them in the drug development continuum. The ultimate goal of this FOA is to bring molecules closer to FDA approval.

The UH2/UH3 Phase Innovation Awards Cooperative Agreement involves 2 phases. The UH2 is to support a project with specific milestones to be accomplished at the end of the 2-year period. The UH3 is to provide funding for 3 years to a project that successfully completed the milestones set in the UH2. UH2 projects that have met their milestones will be administratively considered by NIDA and prioritized for transition to the UH3 phase. Investigators responding to this FOA must address both UH2 and UH3 phases.

The NIDA Translational Avant-Garde Award complements NIDA s traditional investigator-initiated grant programs by supporting applications focused on the translation of basic scientific discoveries into medications. Research on the neurobiology of addiction has identified an increasing number of genetic, cellular and biological targets where a therapeutic intervention could benefit patients with SUDs. Translation of these scientific discoveries into therapeutic interventions requires deliberate, persistent, and focused commitment and effort.

The NIDA Translational Avant-Garde Award provides this level of support and commitment by offering a scientist the unique opportunity to realize the therapeutic potential of his/her scientific discoveries and advance them one step closer to regulatory approval. Projects responsive to these coupled announcements could be undertaken at any point along the drug development continuum, from late discovery (i.e., lead optimization/early safety) up to Proof of Concept (POC) clinical trials.

Through this FOA, NIDA seeks to attract exceptionally-talented investigators to the mission of expanding the number and breadth of lead compounds in the pipeline for drug addiction treatment, optimizing these leads, and/or advancing them to clinical testing.

Applicants for the NIDA Translational Avant-Garde award are expected to have a robust body of background data in the basic science and early discovery phases to be poised for transition of a lead compound to the pre-clinical and clinical phases of medications development. NIDA expressly seeks to promote research projects that are ready for translation and can accelerate the development of new medications. Accordingly, only those applicants who conduct research studies positioned between late pre-clinical discovery (i.e., lead optimization and beyond) and POC clinical trials are appropriate to apply. That is, for small molecules, the earliest stage of eligibility for this Award is already having small-molecule compounds with proof of desired pharmacological activity. For biologics, the profiling of promising product candidates in animal models of drug addiction will be allowed as the earliest entry point.

Applications focusing solely on novel target identification/validation, generation of new animal models, development/testing of new human laboratory models, or mechanistic studies of the neurobiology of addiction are considered non-responsive for the NIDA Translational Avant-Garde Award.

Applications submitted in response to this FOA may focus on studying 1) new chemical entities (NCEs), 2) already-marketed pharmacotherapies, 3) biologics (e.g., immunotherapies such as vaccines and antibodies, enzymes, and gene therapies), 4) combinations of medications, and/or 5) new delivery devices/technologies.

The medications investigated for SUDs may target one or more of the neuropathological mechanisms, the various clinical stages, and/or the medical/psychiatric complications of one or multiple SUDs.

This FOA encourages, but is not limited to, studies of medications for SUDs in the following areas:

• Chemistry and Pharmaceutics: lead compound optimization, formulation or drug-delivery technology, prodrug, proteinaceous (e.g., vaccines and antibodies).
• Preclinical Development: drug interaction studies between medications and drugs of abuse, evaluation of compound safety and/or efficacy in established animal models, and pharmacokinetic and pharmacodynamic studies of potential therapies for SUDs.
• Clinical Development: Phase I - Evaluation of the pharmacokinetics, safety, tolerability, dose-ranging, and/or initial efficacy in human subjects. Phase II - Proof-of-concept, pilot studies, safety and efficacy testing in a larger sample of human subjects.

It is expected that all applications involving treatment seeking individuals will provide a behavioral therapy component. However, the scope of this FOA does not include the evaluation of the safety and/or efficacy of psychosocial interventions.

Awardees of this FOA may collaborate with pharmaceutical companies, academic investigators, and NIH scientists. Awardees are encouraged to make their individual datasets and aggregated datasets available for data sharing to other investigators when appropriate.

All studies involving NIH defined clinical trials must have a Data and Safety Monitoring Plan (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html). The DSMB is responsible for reviewing interim and final data, and recommending whether the study should be continued, modified, or terminated. The DSMB reviews the protocols, monitors recruitment, adverse events, data quality, outcome data, and overall study performance. For those clinical trials that required by this policy to have a Data and Safety Monitoring Board (DSMB), the investigators have the option of having their study monitored the DSMB of the Division of Pharmacotherapies and Medical Consequences of Drug Abuse (DPMCDA) of NIDA. This DSMB reports to the Director, DPMCDA. The awardees also have the option to use another DSMB. Applications involving one or more clinical trials must state that the clinical trial(s) will be monitored by a DSMB, which could be the DPMCDA sponsored DSMB. The DSMB to be used for each trial will be agreed upon with NIH prior to award.

HIV/AIDS Counseling and Testing Policy for the National Institute on Drug Abuse: In light of recent significant advances in rapid testing for HIV and in effective treatments for HIV, NIDA has revised its 2001 policy on HIV counseling and testing. NIDA-funded researchers are strongly encouraged to provide and/or refer research subjects to HIV risk reduction education and education about the benefits of HIV treatment, counseling and testing, referral to treatment, and other appropriate interventions to prevent acquisition and transmission of HIV. This policy applies to all NIDA funded research conducted domestically or internationally. For more information seehttp://grants.nih.gov/grants/guide/notice-files/NOT-DA-07-013.html.

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects: The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects. Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's Web site at http://www.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community. Please see (http://www.drugabuse.gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding-) for details.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit: NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.phenxtoolkit.org). Please see NOT-DA-12-008 (http://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html) for further details.

If applicable, investigators should include male and female samples and data analysis to evaluate potential sex/gender differences. When samples or analysis are not proposed, scientific justification should be provided.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are 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

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.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

The PD(s)/PI(s) should have sufficient expertise in drug discovery and development and/or translational research and devote at least 51% or 6.1 person months to the research activities supported by this Award.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

[email protected].

Applicants are encouraged to send the letter of intent by email to the email address above but as an alternative the letter may also be sent to:

Director - DA-15-010
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Suite 4243, MSC 9550
Bethesda, MD 20892-9550

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

The PD(s)/PI(s) should devote at least 51% or 6.1 person-months of his/her research effort to activities supported by this award.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy:

If applicable, investigators should include male and female samples and data analysis to evaluate potential sex/gender differences. When samples or analysis are not proposed, scientific justification should be provided.

Applicants are encouraged to provide a decision tree for the compound testing, when appropriate. This decision tree should include the go/no-go decision points.

Applicants should provide the entry and exit points of the proposed research in the medications development continuum.

All clinical trial applications must include methods to evaluate subjects' compliance with the study medications.

Milestones and UH2/UH3 Transition

Applicants must plan for both a UH2 and a UH3 phase. The UH2 section must include a description of an entry point and the milestone(s) that will be reached at the end of this phase. To successfully transition to the UH3 phase, the project should reach the milestones outlined in the application. The application should provide quantifiable metrics to determine success of the UH2.

Additional milestone(s) may be negotiated before or after funding decisions have been made.

Examples of milestones may include completing:
Lead optimization efforts of a small molecule to improve chemical, pharmacokinetic, pharmacological and safety properties of a potential clinical candidate.
Safety and efficacy profile of a promising small molecule or biologic (vaccines, antibodies, or enzymes) product candidate in animal models of drug addiction.
Scale-up production methods and the manufacturing of the clinical candidate under current Good Manufacturing Practices (cGMP)
Pre-formulation, formulation and stability testing efforts
IND-enabling studies, including pre-clinical toxicology
A new formulation of a marketed medication to be tested for SUDs
The development of a new combination product to be tested for SUDs
Phase Ia clinical studies to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of a new medication or biologic
Phase Ib clinical studies to assess the interaction between the new medication and the targeted drug of abuse, in terms of safety, tolerability, and possible pharmacokinetic and pharmacodynamic interactions
POC clinical trials.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications submitted for the January 25, 2015 due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.
• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

Important reminders:

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 the NIDA, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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.

For this particular announcement, note the following:

The UH2/UH3 phased innovation cooperative agreement supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An UH2/UH3 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the UH2 and UH3 phases.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? 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? Has the applicant made a compelling case that proposed project is translational?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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 particular, is there sufficient evidence of the investigator’s expertise in drug discovery and development and/or translational research?

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? Does the investigator provide sufficient evidence that the compound or compounds to be evaluated represent an innovative pharmacotherapy for SUDs? Is the proposed work likely to advance the development of a compound toward regulatory approval by the FDA for a SUD indication?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

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 children, justified in terms of the scientific goals and research strategy proposed?

Does the research project clearly identify a treatment outcome of the research efforts? Does the research project represent a significant leap from incremental knowledge-gathering to a practical application (a translational endpoint)? Does the application provide clear entry and exit points on the drug development pathway? Are they well-defined and well-justified? Does the application acknowledge potential problem areas and consider alternative approaches? Does the application provide milestones that can be achieved in the 2-year period of the UH2 grant?

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?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the six 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.

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 children 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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Non Applicable

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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 Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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 the NIDA, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. 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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described 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.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

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 at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• All aspects of their study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators.
• The awardee agrees to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the study including those outlined under "NIH Responsibilities".
• Awardees will participate in annual meetings of the awardees and will support any committees, task forces, and advisory panels as needed.
• Upon implementation of the protocol, each field center, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, patient management, and data collection.
• Support or other involvement of industry or any other third party in the study--e.g., participation by the third party; involvement of project resources or citing the name of the project or the NIH support; or special access to project results, data, findings, or resources--may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur with the concurrence by NIH Program Officer to ensure objectivity of research.
• Obtaining prior written approval of the NIH Grants Management Specialist in consultation with the NIH Program Officer for a change in any of the key personnel identified in the Notice of Award.
• Award recipients will own the rights in any tangible work products created under the terms of the cooperative agreement. Work products may include such things as research reports, papers, research, findings, training curricula, data sets, books, patient tools, and other materials. All such products shall be made accessible to the public and are subject to Government rights of access, as appropriate, in accordance with NIH’s legal directives and authorities.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The NIH Project Scientist will have access to the data and work with the PD(s)/PI(s) to ensure the objectives of the program are being met. The primary responsibility for the program resides with the awardee, although specific tasks and activities will be shared among the awardee and the NIH Project Scientist.
• 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.
• NIH support of this study is contingent upon adequate participant recruitment based on the Grantee’s Milestone Accrual Plan submitted at the time of funding.
• The Grantee is expected to demonstrate best effort compliance. Failure to achieve minimally acceptable milestone recruitment levels may result in the withholding future support and or negotiating an orderly close-out of this study.
• NIH staff will act as a resource and facilitator for activities of the awardee with non-HCS researchers and other NIH, DHHS, or other federally-sponsored research networks that may be relevant to this effort.
• Serve as a resource to provide scientific/programmatic support during the accomplishment of the clinical trial 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.
• Participate in the monitoring of issues relating to recruitment, retention and follow-up of study participants, and monitoring of data integrity and quality control through consideration of the annual reports, site visits, patient logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting patient enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting as needed to the administration and evaluation core.
• Assist in the development and modification of study protocols.
• NIH staff will interact with the PD(s)/PI(s) on a regular basis to monitor progress. Monitoring may include: regular communication with the PD(s)/PI(S) and his staff, periodic site visits for discussion with the awardees research team, observation of field data collection and management techniques, fiscal reviews, and other relevant stewardship matters.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

The PD(s)/PI(s) provide, in concert with the NIH staff, support necessary to ensure that sites and investigators, and NIH and other research partners fully comply with federal regulatory requirements, including but not limited to those relating to human subjects protections, informed consent, and reporting of adverse events.

Awardees and NIH will jointly develop appropriate confidentiality procedures for data collection, processing, storage and analysis to ensure the confidentiality of data on individual health care provider organization patients, health care providers and other institutions.

All awardees and NIH will cooperate to ensure the timely and broad dissemination of lessons learned, to inform researchers and health care systems engaged in research in health care settings.

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. It will have three members: a designee of the investigator chosen without NIH staff voting from among the PI of the FOA, 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.

Not Applicable

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report 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.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: [email protected]

Ivan D. Montoya, M.D., M.P.H.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-8639
Email: [email protected]

Mark Swieter, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1389
Email: [email protected]

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-253-8729
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.