National Institutes of Health (NIH)
National Center for Advancing Translational Sciences (NCATS)
Funding Opportunity Title
Limited Competition for NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules (UH3)
UH3 Exploratory/Developmental Cooperative Agreement Phase II
Funding Opportunity Announcement (FOA) Number
Companion Funding Opportunity
PAR-12-203, Pre-application for the NIH-Industry Pilot Program, Discovering New Therapeutic Uses for Existing Molecules (X02); RFA-TR-12-004, Limited Competition for the NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules (UH2/UH3)
Catalog of Federal Domestic Assistance (CFDA) Number(s)
Funding Opportunity Purpose
The National Center for Advancing Translational Sciences (NCATS) seeks to develop a therapeutics discovery pilot program that will explore new therapeutic uses for proprietary drug candidates (Agents) across a broad range of human diseases. This innovative program will match Agents and associated data from pharmaceutical company partners with the best ideas for new therapeutic uses from the biomedical research community.
PAR-12-203 encourages X02 pre-applications for the NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules. The X02 pre-application is the first step in the application process for RFA-TR-12-004 and RFA-TR-12-005; applicants must read both of the companion FOAs. The X02 pre-applications will be evaluated by outside scientific experts.
Investigators whose X02 pre-applications are judged to be the most meritorious will be notified of the opportunity to submit a UH3 application under this FOA or a UH2/UH3 application under RFA-TR-12-004.
The UH3 will support milestone-driven Phase IIa proof of concept trials to assess the potential clinical efficacy of an Agent, made available for this program by the pharmaceutical partners, for its potential new use in the proposed disease population. The project period for the UH3 is up to two years.
June 12, 2012
Open Date (Earliest Submission Date)
November 17, 2012
Letter of Intent Due Date
Application Due Date(s)
December 17, 2012, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)
Scientific Merit Review
Advisory Council Review
Earliest Start Date(s)
December 18, 2012
Due Dates for E.O. 12372
Required Application Instructions
It is critical that applicants follow the instructions in the SF 424 (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
In April 2011, NIH convened an NIH-Industry Roundtable that included a group of senior leaders and experts from the pharmaceutical industry, government, academia, and the non-profit sector to explore opportunities to foster new NIH-industry partnerships that facilitate drug rescue and repurposing. Some of the challenges that were identified include: resource implications (the time and resources for a pharmaceutical company to maintain, update, and organize their compound libraries for drug rescue and repurposing); patent considerations (off-patent compounds or compounds whose patents are close to expiring, may not be attractive to industry because the financial return and market incentives for the product may be limited); and transactional hurdles related to developing, negotiating and implementing appropriate legal agreements among the parties, including addressing such concerns as intellectual property rights and liability. The Roundtable participants agreed that more can and should be done to increase engagement and partnerships in drug rescue and repurposing and to enhance the success of these efforts. In response to one of the recommendations from the meeting, NCATS has developed an NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules.
This Program will fund research to identify new therapeutic uses of proprietary drug candidates (compounds and biologics), made available by pharmaceutical company partners, to benefit public health. NCATS is especially interested in projects that address areas of unmet medical need. NCATS plans to initiate the research program as a pilot with a limited set of high-quality drug candidates (Agents) contributed by the pharmaceutical company partners. If the pilot is successful, the Program may be expanded to include additional pharmaceutical or biotechnology company partners, Agents, and new therapeutics discovery projects.
The Program intends to support innovative ideas from the biomedical research community for the discovery of potential therapeutic uses of these Agents in previously unexplored disease areas. Proof of concept studies can include, as examples, use of an Agent as a stand-alone intervention or as an adjunctive intervention (if there is no evidence of drug-drug interactions with the proposed standard of care treatment). Strategies to inform the selection of patients for proposed new uses of the Agents are of interest.
For this FOA, Phase IIa proof of concept trials are defined as studies designed to explore new hypotheses and to assess whether the Agent demonstrates an early signal of efficacy in the targeted patient population, typically 150 subjects or less. In addition to clinical benefit, Phase IIa trials also include assessments of safety, tolerability, and PD/PK response of the Agent.
The UH3 activities will include exploratory, phase IIa proof of concept trials designed to establish the relationship between the magnitude and duration of target modulation and clinical efficacy of the Agent in the proposed disease population. The inclusion of biomarkers in the design of the study is encouraged, when appropriate: e.g., the inclusion of PK/PD biomarkers to assess target engagement, exposure and functional pharmacological activity of the Agent (see, Morgan P., et. al, Drug Discov. Today (2012), doi:10.1016/j.drudis.2011.12.020), or the use of molecular markers of disease, pharmacogenomics, or other biomarkers as patient selection strategies. The goals of the Phase IIa proof of concept trials are to determine that the Agent modulates the target/mechanism and shows potential for efficacy in the proposed disease population, thereby de-risking further clinical development of the Agent for a new therapeutic use that has not previously been explored. The duration of the UH3 project period is up to two years.
In cases where the proof of concept studies are successful, it is anticipated that the pharmaceutical company partner will pursue further clinical development of the Agent for the new therapeutic use, including requisite Phase III clinical trials, ultimately commercializing the novel therapeutic intervention for the new disease indication whenever feasible.
The submission of an X02 pre-application is a necessary
first step in applying for an award under this FOA or the companion FOA, RFA-TR-12-004 (UH2/UH3); applicants must also read both companion FOAs prior to submitting an
X02 pre-application. Pre-applications submitted in response PAR-12-203 will be evaluated by outside scientific experts. X02 applicants will
receive feedback on the scientific merit, technical feasibility, administration
and management plans, and overall potential for
impact of the science proposed
X02 applicants invited to submit a UH3 application must contact the pharmaceutical company partner for the Agent that was selected for studies in the X02 pre-application, and execute an appropriate Confidential Disclosure Agreement (see template CDAs). Under the CDA, the applicant and pharmaceutical company partner will exchange confidential information (e.g., additional information on the Agent and studies to test the proposed new therapeutic use of the Agent), as deemed necessary, to initiate discussions. Subsequently, it is anticipated that a Collaborative Research Agreement (CRA) between the applicant and the pharmaceutical company partner will be the vehicle through which the applicant obtains permission to work with the Agent on the research project plan for the UH3 application. The applicant must provide the NIH with documentation of access to the Agent and associated data needed for filing an investigator-sponsored Investigational New Drug (IND) Application and for conducting the proposed clinical trial (e.g., an executed CRA).
A key component of this FOA is the formation of collaborative partnerships between the biomedical research community and industry partners. NCATS has executed a Memorandum of Understanding (MOU) with each of the pharmaceutical company partners to provide a framework under which specific proprietary Agents will be provided by these partners to the program awardees. Template agreements have been developed for this program: Confidential Disclosure Agreements (CDAs) and Collaborative Research Agreements (CRAs) between the pharmaceutical company partner and the applicant. These template agreements have been developed to streamline interactions among the parties for the Program, and it is anticipated that applicants will use the agreements. Investigators should work with their institutional technology transfer or sponsored research office to finalize the terms and conditions of the CDA and CRA for the selected Agent prior to submission of a UH3 application. A successful UH3 application will be contingent on the applicant’s ability to provide the NIH with documentation of access to the selected Agent and associated data needed for filing an investigator-sponsored IND in order to conduct the proposed clinical trials (e.g., an executed CRA or letter from the pharmaceutical partner).
Agents Available for the Program
The list of Agents and non-confidential information can be found at http://www.ncats.nih.gov/research/reengineering/rescue-repurpose/therapeutic-uses/directory.html.
Timeline for the Program
August 14, 2012
Submission date for X02 pre-application
Evaluation of pre-application by outside experts
Late September 2012
Notification of opportunity to submit a full UH2/UH3 or UH3 application
December 17 2012
Submission date for UH2/UH3 applications
Scientific merit review for UH2/UH3 applications
NCATS Advisory Council review of applications
Earliest possible start date for awarded grants
Application Types Allowed
The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards
NCATS intends to commit up to $20 million in FY 2013 to fund six to eight UH2/UH3 or UH3 awards in response to this FOA and the companion FOA (RFA-TR-12-004). Future year amounts will depend on annual appropriations.
Application budgets are not limited, but need to reflect actual needs of the proposed project.
Award Project Period
The total project period for a UH3 application submitted in response to this FOA may not exceed two years.
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.
This FOA is a limited competition for those applicants who submitted a pre-application in response to PAR-12-203 [X02] and have been notified of the opportunity to submit a UH3 application.
Applicant organizations must complete the following
registrations as described in the SF 424 (R&R) Application Guide to be
eligible to apply for or receive an award. Applicants must have a valid Dun and
Bradstreet Universal Numbering System (DUNS) number in order to begin each of the
All Program Directors/Principal Investigators (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.
This FOA is a limited competition for those applicants who submitted an X02 pre-application in response to PAR-12-203 [X02] and have been notified of the opportunity to submit a UH3 application.
For these UH3 applications, the PD/PI must be the same PD/PI listed on the X02 pre-application. For UH3 applications proposing multiple PD(s)/PI(s), the contact PD/PI must be the same PD/PI listed as the contact on the X02 pre-application. The contact PD/PI is strongly encouraged to continue the multiple PD(s)/PI(s) leadership identified in the X02 pre-application if notified of the opportunity to submit a UH3 application.
NIH Intramural Research Program (IRP) investigators are eligible to apply for the UH3 FOA, subject to the availability of intramural funds to support the project. IRP investigators can apply as PD(s)/PI(s), as multiple PD/PIs in conjunction with extramural investigators (http://grants.nih.gov/grants/multi_pi/index.htm), or as collaborators with extramural academic or biotechnology company investigators. Intramural Research Investigators cannot request extramural funds. For more information, see Section 6, Other Submission Requirements and Information.
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.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.
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, 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.
The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Instructions for Preparing a UH3 Application
1. The selected Agent and new therapeutic use should be the same as proposed in the X02 pre-application.
2. UH3 applications are limited to 12 pages for the Research Strategy section including milestones, timeline and future plans.
3. See Section 6, Other Submission Requirements and Information for additional information.
The one-page Specific Aims section should include the following information:
1. Define the aims of the Phase IIa proof of concept clinical trial.
a. The aims should include proposed clinical trials to determine target modulation and efficacy.
b. The clinical data resulting from the UH3 component should provide sufficient evidence that the drug candidate is safe and well-tolerated for sustained administration in the proposed dose range, modulates the target/mechanism and a biomarker of PD effect, and has a signal of efficacy in the disease population.
Within the 12-page Research Strategy, provide the following information:
1. Background & Significance
a. Identify the Agent, its known pharmacologic mechanism of action or target, and route of administration.
b. State the biological rationale or hypothesis for the new therapeutic use of the Agent
c. Indicate the disease, clinical population, and public health need that will be addressed by the proposed new use of the Agent.
1). Address the global burden of disease, which patients will benefit, how they will benefit, how use of the Agent will be superior to current therapy options, and potential for impact on public health.
2. Preliminary Studies
a. The Preliminary Studies will contain, but are not limited to, data and information that validate the feasibility of conducting studies to address the specific aims.
1). Evidence that the target or specific pathway is involved in the disease pathology.
2). Any additional relevant information on the Agent (e.g., availability of pharmacokinetics (PK) and pharmacodynamics (PD) markers, any exclusions or restrictions in the Agent's use).
3). Data to support the selection of dose and exposure of the Agent based on available PD/PK biomarkers or functional pharmacological activity.
4). Information on the risk/benefit of the Agent to patients and the operational feasibility of conducting clinical trials to address the specific aims.
a. Describe and justify the design of the Phase IIa proof of concept trial to assess activity of the Agent to change the disease state in the proposed patient group.
1). Describe the use of PK and PD biomarkers, when available, to select the dose and exposure of the Agent at the target site of action, binding at the target, or expression of functional pharmacological activity of the Agent at the target site of action.
2). Specify the duration of studies, based on safety data available for the Agent, and whether the new use of the Agent is for treatment of an acute or chronic disease.
3). Specify dose range, route of administration, and amount of Agent needed based on the formulation available for the selected Agent.
4). Discuss plans for timely filing of an IND and expedited Institutional Review Board (IRB) approval.
b. Define the patient selection strategy.
c. Define the clinical end points or outcome measures and the power calculations that determine the size of the trial.
1). The sample size, power, and duration of the trial should be justified for the specific disease population.
2). Discuss alternative statistical plans to show potential therapeutic benefit in Phase IIa proof of concept trials with small sample size.
4. Milestones and Timeline
a. The application must include clearly-specified, well-defined milestones, go/no go decision points, and timelines for assessing progress.
b. Provide a clear description of the timeline, interim milestones and go/no decision points during the course of the clinical trial.
c). Identify any impediments that could require an addendum to the research plan, milestones, or timeline with a discussion of alternative approaches.
d). Provide detailed quantitative criteria by which milestone achievement will be assessed.
e). Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal.
5. Future Plans
a. Describe the commercial potential of the Agent as a development candidate and potential challenges for commercialization of the Agent for the new disease indication.
The following sections are not part of the Research Strategy but must be included in the application:
Protection of Human Subjects
Address Human Subjects protections for any clinical research anticipated in the period of the grant, as described in the PHS 398 application instructions. Human subjects protection should be detailed for the proposed Phase IIa proof of concept trial. Describe in detail known information and possible contingencies regarding potential risks and benefits to participation, and plans to obtain informed consent. Include anticipated plans for data and safety monitoring commensurate with potential risks inherent in Phase Ib and IIa clinical trials.
Inclusion of Women and Minorities, Inclusion of Children
Provide description of plans for adequate inclusion of minorities and women in the clinical sample, or justify any exclusions. Include a targeted/planned enrollment table for each of the planned studies involving human subjects. Provide description of plans for adequate inclusion of children in the clinical sample, or justify any exclusions. Inclusion plans should be provided separately for each stage of the award.
Letters of Support
Include a letter of support from the pharmaceutical company partner documenting: access to the Agent and associated data needed for filing an investigator-sponsored IND for the Agent to conduct the proposed clinical trials (e.g., a letter indicating that a CRA has been executed, that the PD/PI has the right to cross-reference specific sections of the pharmaceutical company partner's IND/Drug Master File, etc.).
Resource Sharing Plan
Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:
Appendices are not allowed for this FOA and will not be accepted. Do not use the other attachments section.
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications via 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.
Applicants are responsible for viewing their application 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 SF 424 (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.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(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.
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 Central Contractor Registration (CCR). 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 by the Center for Scientific Review and responsiveness by NCATS. Applications that are incomplete and/or nonresponsive will not be reviewed.
In order to expedite review, applicants are requested to notify the NCATS Referral Office by email at email@example.com when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application:
Bonnie B. Dunn, PhD
Scientific Review Officer
Office of Grants Management and Scientific Review
National Center for Advancing Translational Sciences
National Institutes of Health
6701 Democracy Blvd., Room 1066
Bethesda, MD 20892-4874
Courier service zip code 20817
301-435-0824 (direct line)
301-435-0811 (Office of Review)
Milestones and Timeline
Prior to funding an application, the Program Official will contact the applicant to discuss the proposed UH3 milestones and potential changes suggested by NIH staff or the NIH review panel. The Program Official and the applicant will negotiate and agree on a final set of approved UH3 milestones. These milestones will be the basis for judging progress towards and completion of the interim milestones in the UH3 stage.
Data and Safety Monitoring
All NIH supported clinical trials, including Phase I trials, require monitoring (NIH Guidance on Data and Safety Monitoring for Phase I and Phase II Trials NOT-OD-00-038). Although a general DSMP may be appropriate for the initial grant application, NIH staff must review and approve a detailed DSMP with required supporting material prior to the start of any trial. Early discussions with NIH staff are encouraged to prevent delays. The proposed level of monitoring should be commensurate with risk. For many studies, the grantee manages data and safety monitoring. In specific cases, NIH may establish and manage independent data and safety monitoring boards (DSMBs) for trials that utilize NIH grant resources. For Phase IIa proof of concept trials, this level of monitoring may be appropriate if the studies have multiple clinical sites, are blinded (masked), or employ particularly high-risk interventions or vulnerable populations. In these cases, NIH establishes a charter, appoints members and an executive secretary, provides conflict of interest vetting, and supports the activities of the DSMB. The NIH is responsible for continuing oversight even if monitoring is delegated to the grantee. All other NIH Policies related to clinical research, including trials, will also apply to the UH3 award.
Documentation of access to the Agent proposed for use in the UH3 studies
Consistent with achieving the goals of the Program, the applicant must provide the NIH with documentation of access to the Agent, which was proposed in the X02 pre-application, and associated data needed for conducting the proposed pre-clinical studies and for filing an investigator-sponsored IND in order to conduct the proposed clinical trials (e.g., an executed CRA or letter from the pharmaceutical partner).
Additional Instructions for NIH Intramural Research Program (IRP) Applicants
1. IRP investigators can apply as PD(s)/PI(s), as multiple PD(s)/PI(s) in conjunction with extramural investigators (http://grants.nih.gov/grants/multi_pi/index.htm), or as collaborators with extramural academic or biotechnology company investigators, pending the availability of intramural funds to support the project.
2. IRP investigators and laboratories cannot request extramural funds.
3. An official letter from the Scientific Director, which indicates approval of the IRP scientist's role as PD/PI or as collaborator in the project, must be included as a letter of support in the UH3 application. The letter must specify the Scientific Director's commitment of intramural research funds to support the IRP investigator's proposed UH3 project or project component.
4. Justification must be provided for all proposed personnel (Federal employees and contract staff) who will be committing effort on the project although no funds are requested in the application. Applicants should indicate the number of person-months devoted to the project, even though no extramural funds are requested for salary and fringe benefits.
5. If selected, NIH IRP scientists, in conjunction with their respective technology transfer representative, will need to contact the pharmaceutical company partner participating in this Program for the selected Agent to: execute a CDA to exchange confidential information, and negotiate a PHS Cooperative Research and Development Agreement (CRADA), Clinical Trials CRADA, or other similar type of agreement, to incorporate, as appropriate, the terms of the CRA.
6. If selected, NIH intramural scientists will participate in this program as PD(s)/PI(s) in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH.
7. Should an extramural application include the collaboration with an IRP scientist, no extramural funds may be requested to support the IRP scientist or IRP laboratory.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115,
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.
Reviewers will provide an overall impact/priority 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? Does the proposed project have the potential for influence with regard to a new therapeutic use for the Agent in a disease or disorder for which there is no current treatment or clinical outcome, or for which the current standard of care has considerable disadvantages or very limited utility? Is there a strong biological rationale for the indicated therapeutic use?
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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? What are the qualifications, experience, and commitment of the personnel involved in the proposed therapeutics discovery project? Do the PD(s)/PI(s) have the scientific and organizational vision and experience to serve effectively as the Director(s) of the project? Is there evidence of sufficient management capabilities that include fiscal administration, personnel management, planning, and budgeting? Does the investigative team have the requisite competencies and experience with clinical trials recruitment and execution? Do the PD(s)/PI(s) demonstrate relevant experience and knowledge of the public-private partnerships?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
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? What is the evidence for the biological hypothesis for the proposed new use of the
Agent (its pharmacologic mechanism of action or target) and relevance of the
biology to therapeutic intervention in the proposed disease that suggests
likelihood of successful completion of Phase IIa proof of concept trials during
the two-year project period? Are procedures in place for quality control and
quality assessment of the clinical procedures? Are data management and support
procedures developed sufficiently to allow tracking of clinical trial data? Have
the PD(s)/PI(s) provided an operational plan for managing the necessary
collaborations between and among clinical plan investigators and the
pharmaceutical company partner? Is a plan in place for timely submission of an
IND application for the clinical trial, expedited IRB review and approval, and timely
patient recruitment? What is the likelihood of the proposed project in meeting
the goals under the compressed two-year timeline of the FOA?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, 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? Are facilities adequate for the overall functions of the project and to implement the goals of the program? Is there evidence for institutional commitment to the program, including provision of space, and other measures of institutional commitment? Are the research environment and resources, including equipment and facilities, adequate? Does the scientific environment indicate the potential for a multi-disciplinary approach involving teams of investigators? Is a team in place to rapidly implement the proposed trial?
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/priority score, but will not give separate scores for these items.
Milestones and Timeline
Are appropriate, evaluative milestones provided for the UH3 stages clearly defined? Are the UH3 milestones feasible, well developed and quantifiable with regard to the specific aims? Is the timeline feasible for the UH3? Are the go/no go decision points, recruitment goals, and timelines appropriate for the Phase IIa proof of concept trial in the UH3?
Protections for Human Subjects
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 Human Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
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.
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/priority score.
Applications from Foreign Organizations
Select Agent Research
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).
Resource Sharing Plans
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) Genome Wide Association Studies (GWAS).
Reviewers will also comment on whether the applicant has addressed a plan and timeline for sharing positive or negative clinical trials data (e.g., through ClinicalTrials.gov, publications, or public website.
Budget and Period of Support
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 NCATS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to NCATS with potential secondary assignment based on the proposed disease population 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 NCATS Advisory Council. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD(s)/PI(s) 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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The Project Scientists will:
The Program Official will:
Areas of Joint Responsibility include:
Each awardee's project will have a Steering Committee. The Steering Committee will serve as the operational governing board for the project. The Steering Committee will include: the PD(s)/PI(s), key personnel, the pharmaceutical company collaborator or consultant as an ex officio member, the NIH Project Scientist, the NIH Program Official, and external scientist(s).
The Steering Committee will:
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 Steering Committee 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.
When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) 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.
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
eRA Commons Help Desk (Questions regarding eRA Commons
registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
We encourage inquiries and welcome the opportunity to answer questions from potential applicants.
For technical questions regarding the FOA (mechanisms, partnerships, application content or scientific management of the cooperative agreements), please contact:
Christine Colvis, Ph.D.
Therapeutics Discovery Program
National Center for Advancing Translational Sciences, NIH
6701 Democracy Blvd., Democracy I, Rm. 924
Bethesda MD 20892-4874 (Regular mail)
Bethesda MD 20817 (FedEx)
Telephone: See Contact List
Heng Xie, M.D., M.P.H., Ph.D.
Supervisory Medical Officer
Division of Clinical Innovation
National Center for Advancing Translational Sciences, NIH
6701 Democracy Blvd., Democracy I, Rm. 908
Bethesda MD 20892-4874 (Regular mail)
Bethesda MD 20817 (FedEx)
For questions related to proposed new therapeutic uses of
the Agents in specific disease areas, Institute or Center contacts can be found
Bonnie B. Dunn, Ph.D.
Office of Grants Management and Scientific Review
National Center for Advancing Translational Sciences (NCATS)
6701 Democracy Boulevard, Room 1066, MSC 4874
Bethesda, MD 20892-4874
Bethesda, MD 20817 (for Express/Courier Service)
Telephone: 301-435-0824 (direct line)
Telephone: 301-435-0811 (Office of Review)
Office of Grants Management
National Center for Advancing Translational Sciences (NCATS)
6701 Democracy Blvd, Room 1051
Bethesda, MD 20892 (20817 for express delivery)
Office of Grants Management
National Center for Advancing Translational Sciences (NCATS)
6701 Democracy Boulevard, Room 1051, MSC 4874
Bethesda, MD 20892
Bethesda, MD 20817 (for Express/Courier Service)
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, 479 and 480 of the Public Health Service Act as amended (42 USC 241, 287 and 287a) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.
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