Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
U01 Research Project Cooperative Agreements
Reissue of PAR-18-633
See Notices of Special Interest associated with this funding opportunity
NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available
NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
See Notices of Special Interest related to this funding opportunity
PAR-21-082 - NIAID SBIR Phase II Clinical Trial Implementation Cooperative Agreement (U44 Clinical Trial Required)
PAR-20-270 - NIAID Clinical Trial Planning Grant (R34 Clinical Trials Not Allowed)
93.855
This Funding Opportunity Announcement (FOA) encourages cooperative agreement applications for implementation of investigator-initiated, high-risk clinical trials and mechanistic studies associated with high-risk clinical trials. Mechanistic work in clinical trials may be of great value because it promotes the understanding of human diseases and the development of future therapeutic modalities.
Investigators are encouraged to visit the NIAID website for additional information about the research mission and high-priority research areas of the NIAID (https://www.niaid.nih.gov/research/role).
Only one clinical trial may be proposed in each NIAID Clinical Trial Implementation Cooperative Agreement (U01) application.
February 12, 2021 New open date to accommodate applications for NOT-AI-20-065. All other aspects of this FOA remain the same. (Old Date: April 14, 2021)
30 days prior to the application due date
May 14, 2021; September 13, 2021; January 14, 2022; May 13, 2022; September 13, 2022; January 13, 2023; May 13, 2023; September 14, 2023; January 13, 2024
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
May 14, 2021; September 13, 2021; January 14, 2022; May 13, 2022; September 13, 2022; January 13, 2023; May 13, 2023; September 14, 2023; January 13, 2024
All applications are due by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on the listed date(s).
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
Non-AIDS Applications: October 2021; February 2022; June 2022; October 2022; February 2023; June 2023; October 2023; February 2024; June 2024
AIDS Applications: August 2021; December 2021; April 2022; August 2022; December 2022; April 2023; August 2023; December 2023; April 2024
Non-AIDS Applications: January 2022; May 2022; October 2022; January 2023; May 2023; October 2023; January 2024; May 2024; October 2024
AIDS Applications: October 2021; January 2022; May 2022; October 2022; January 2023; May 2023; October 2023; January 2024; May 2024
Non-AIDS Applications: March 2022; July 2022; December 2022; March 2023; July 2023; December 2023; March 2024; July 2024; December 2024
AIDS Applications: December 2021; March 2022; July 2022; December 2022; March 2023; July 2023; December 2023; March 2024; July 2024
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from 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.
Purpose
This Funding Opportunity Announcement (FOA) encourages cooperative agreement applications for implementation of investigator-initiated, milestone driven, high-risk clinical trials and mechanistic studies associated with clinical trials. Mechanistic work in clinical trials may be of great value because it promotes the understanding of human diseases and the development of future therapeutic modalities.
A clinical trial is defined by NIH as: "A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes." See more at: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html
In addition, any research study that will require a regulatory oversight (such as Investigational New Drug [IND] or Investigational Device Exemption [IDE]) will be in the scope of this FOA.
The proposed trial must be hypothesis-driven, related to the research mission of the NIAID, and address a research area considered a high priority by the Institute. For HIV-related clinical trials, NIAID encourages projects that integrate biomedical and behavioral interventions; studies that explore pathogenesis of HIV infection within the trial are also encouraged.
Background
Over the past three years, NIAID has committed over $5.5 billion to clinical research, of which $2.5 billion was devoted to clinical trials and supportive activities. Clinical trials are one research strategy NIAID uses to improve the understanding of the clinical mechanisms of infectious, immunologic, and allergic diseases or to improve prevention, diagnosis, and treatment. For additional information about the mission, strategic plan, and research interests of the NIAID, applicants are encouraged to consult the NIAID web site https://www.niaid.nih.gov/research/role.
NIAID Supported Clinical Trials and Infrastructure
Historically, NIAID supports both infrastructure and networks through a variety of funding mechanisms. These resources focus on high-priority disease research areas. Examples include the HIV/AIDS Clinical Trial Networks supported by the Division of AIDS (DAIDS), the Division of Microbiology and Infectious Diseases (DMID) Infectious Diseases Clinical Research Consortium, and the Immune Tolerance Network supported by the Division of Allergy, Immunology and Transplantation (DAIT). NIAID's clinical research infrastructure includes coordinating centers, statistical units, data centers, central laboratories, clinical centers, and other specialized resources. For additional information on DAIDS supported clinical trials refer to the Division of AIDS (DAIDS) Clinical Research Policies and Standard Procedures Documents. For additional information on DAIT Clinical Research Policies and Documents see: https://www.niaid.nih.gov/research/dait-clinical-research-policies-and-standards.
Investigator-Initiated Clinical Trials
Although existing clinical trial programs and infrastructure are crucial to furthering the Institute's research, NIAID recognizes that additional models of clinical research may be important to advancing its research mission; therefore, NIAID has established the investigator-initiated clinical trial program for clinical trials that cannot or will not be conducted through existing NIAID-supported clinical trial networks or infrastructure. This program consists of support for the NIAID Clinical Trial Planning (R34) Grant and the NIAID Clinical Trial Implementation (U01) Cooperative Agreement. The NIAID Clinical Trial Implementation (U01) Cooperative Agreement is designed to support high-risk clinical trials, as defined by NIAID below and in the associated policy statement (see NOT-AI-16-084). NIAID will also utilize the two NIH Clinical Trial FOAs, NIH Research Project Grant (Parent R01 Clinical Trials Required) PA-20-183 and NIH Research Project Grant (Parent R21 Clinical Trial Required) PA-20-194, that invite applications for non-high risk trials. The NIAID Clinical Trial Planning Grant (R34) is available to support planning activities associated with either high- or non-high-risk clinical trials. However, the NIAID Clinical Trial Planning (R34) Grant (PAR-20-270) is not a prerequisite for either NIAID implementation award. If a clinical trial is ready for implementation, and readiness is adequately supported by appropriate documentation, the U01 application may be submitted to the appropriate FOA.
For additional information about NIAID's investigator-initiated clinical trial program, see https://www.niaid.nih.gov/grants-contracts/investigator-initiated-clinical-trial-resources.
Scope
The NIAID Clinical Trial Implementation Cooperative Agreement supports implementation of clinical trials that address high-priority research areas that are well matched with the mission and goals of NIAID. A high-risk clinical trial is defined by the NIAID as having one or more of the following attributes:
A non-high-risk trial would not have any of the attributes listed above; for example, it would involve provision of a routine intervention and administration of a licensed product for an approved indication. Applicants are strongly encouraged to contact NIAID staff listed in Section VII. Agency Contacts for questions concerning the classification of the proposed clinical trial.
Activities and communications regarding all clinical laboratory testing for study participants must comply with US federal regulations [see 42 CFR part 493.2 and 493.3(b)(2)].
This FOA will support the conduct, completion, and analysis of the clinical trial, including activities related to the conduct of the clinical trial, which include but are not limited to the following:
Each NIAID Clinical Trial Implementation award will support the implementation of a single clinical trial that may include more than one intervention. Applications that include more than one clinical trial will not be supported by this FOA.
All clinical trial planning activities must be completed prior to the time of application submission and investigators must be ready to implement the proposed trial at the time of award.
NIAID reserves the right to specify: 1) whether an IND/IDE application should be submitted to an appropriate regulatory agency; 2) the entity (NIAID, primary awardee, etc.) who will hold the IND/IDE; 3) the requirements for the establishment of a DSMB (Data Safety Monitoring Board)/SMC (Safety Monitoring Committee) or the use of an NIAID sponsored DSMB; and 4) the use of other clinical resources such as a Statistical and Clinical Coordinating Center. Applicants are encouraged to discuss those decisions and requirements with NIAID prior to submission of the application.
Mechanistic studies will be supported as part of all clinical trials in this FOA. Any clinical trials supported by DAIT must include mechanistic studies.
Investigators are referred to the Division-specific research policies and standard procedures for protocol templates, guidance, and requirements for clinical trials. See Division of AIDS (DAIDS) Clinical Research Policies and Standard Procedure Documents; Division of Microbiology and Infectious Diseases (DMID) Office of Clinical Research Affairs; Division of Allergy, Immunology, and Transplantation (DAIT) Clinical Research Policies and Standards. Investigators are also referred to NIAID's Clinical Research Toolkit website https://www.niaid.nih.gov/research/trans-niaid-clinical-research-toolkit. Prior to initiation, protocols and consent forms may be subject to review by the NIAID Division. Investigators are strongly encouraged to contact NIAID's program divisions (Agency Contacts) for more information regarding division-specific clinical research policies and procedures.
Milestones
Delineation of milestones is a key characteristic of the NIAID Clinical Trial Implementation Cooperative Agreement. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity.
Applications Not Responsive to This FOA:
Applications proposing the following will be considered non-responsive and will not be reviewed:
For more information, please see the Investigator-Initiated Clinical Trial Questions and Answers at: https://www.niaid.nih.gov/grants-contracts/investigator-initiated-clinical-trials-faqs.
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Need help determining whether you are doing a clinical trial?
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
The scope of the proposed project should determine the project period. The maximum period is 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
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.
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.
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:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
Letter of Intent
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Louis Rosenthal, Ph.D.
Telephone: 240-669-5070
Fax: 301-480-2408
Email: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
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
, with the following additional instructions:
If mechanistic studies are proposed, the application should identify an individual who will have the general responsibility for the scientific and the technical/laboratory aspects of the proposed work. This individual may be the application's PD/PI or a single PD/PI in a multi-PD/PI application.
All instructions in the SF424 (R&R) Application Guide must be followed
, with the following additional instructions:
Because all applications must include detailed scientific and operational plans, funding needs for the entire trial and data analysis period must also be included. In addition to funds required to support clinical trial conduct, the budget should reflect sufficient funds to support independent study monitoring, regulatory submissions, quality management, safety oversight activities. Costs of study drug/product, labeling, distribution should also be delineated, if applicable. If parts of the costs of the trial are to be borne by sources other than NIH, these contributions must be presented in detail. These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented either as part of the requested budget or as Estimated Project Funding. NIAID reserves the right to independently procure drug for the study if that offers cost or other advantages to the clinical trial.
Further information concerning budget preparation may be obtained from the Financial/Grants Management Contact(s) listed in Section VII. Agency Contacts.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: State the goals of the clinical trial and the expected outcome(s). Clearly and concisely present the specific objectives of the trial, as well as a specification of the primary and major secondary endpoints to be measured. Provide a clear explanation of the importance of various endpoints.
Research Strategy: The Research Strategy should include:
Letters of Support: Provide letters of support to document access to or commitment of critical resources, including consortium/site participants, cores, laboratories, pharmacies, data management resources, or other collaborators, including cost-sharing by NIH resources, in the case of intramural collaborators. Investigators are referred to https://www.niaid.nih.gov/research/intramural-collaboration-extramural-funded for additional guidance on Intramural Scientist Collaboration on Extramural Funded Grants. If co-funding or in-kind support is planned from any source (non-NIH sources or NIH sources), letter(s) of commitment (e.g. type, amount and source of support), signed by a business official, on organization letterhead, must be included in the Letters of Support section..
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.
The following modifications also apply:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
The following modifications apply:
Include the informed consent form(s) and, if applicable, assent form(s).
Complete Clinical Protocol: Applicants must include a complete Protocol as part of the Appendix. Investigators should use the NIAID Division-specific Protocol Templates when preparing the complete clinical protocol, and are urged to be succinct. Investigators are also referred to the Trans-NIAID Clinical Research Toolkit website for clinical protocol guidance and templates.
Applications that lack the Complete Clinical Protocol are incomplete and will not be reviewed.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Human Subject instructions:
Section 2 - Study Population Characteristics
2.7 Study Timeline
Include the following:
Completion of data collection time period;
Completion of primary endpoint and secondary endpoint data analyses time period;
Completion of final study report.
Include a series of milestones for completion of the clinical trial and provide contingency plans should there be delays in attaining them.
This section must include:
Section 3 - Protection and Monitoring Plans
3.3 Data and Safety Monitoring Plan
The DSM Plan must address the following areas:
Applications that lack the DSM Plan are incomplete and will not be peer reviewed.
3.5 Overall Structure of the Study Team
This section must include:
A description of the study organization and administration, including, but not limited to: a description of committee structures needed to manage the complexity of the trial; the role of any internal or external advisory committees; the oversight, responsibilities, and coordination of any sites or cores proposed; and the role of any sub-contractors or service providers for personnel or facilities. Note: Do not contact potential members of an external advisory committee and do not propose their names in the application.
Section 5 - Other Clinical Trial-related Attachments
5.1 Other Clinical Trial-related Attachments
The following additional documents should be included as attachments:
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
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 components of participating organizations, NIH. Applications that are incomplete, non-compliant, and/or nonresponsive will not be reviewed.
Requests of $500,000 or more for direct costs in any year
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.
Prior Consultation with NIAID
Consultation with NIAID staff at least 10 weeks prior to the application due date is strongly encouraged for submission of the NIAID Clinical Trial Implementation (U01) Cooperative Agreement application, including new and resubmission applications. If requested, NIAID staff will consider whether the proposed clinical trial meets the goals and mission of the Institute, whether it addresses one or more high priority research areas, and whether it is appropriate to conduct as an investigator-initiated clinical trial, and whether the budget is appropriate. Prior consultation with NIAID staff is required a minimum of 10 weeks prior to the application due date if the budget is equal to or greater than $500,000 direct costs per year for any year of the proposed trial. NIAID staff will not evaluate the technical and scientific merit of the proposed trial; technical and scientific merit will be determined during peer review using the review criteria indicated in this FOA. NIAID staff members are also available to work with potential applicants to determine the risk level of the proposed trial and delineate all documentation that will be needed at the time of application submission. During the consultation phase, if the proposed trial does not meet NIAID's programmatic needs or is not appropriate as an investigator-initiated clinical trial, applicants will be strongly encouraged to consider other Funding Opportunities.
A letter that summarizes the discussion during prior consultation may be obtained from the appropriate NIAID Division Director and attached as in the Cover Letter attachment field on the SF424(R&R) Cover form.
For further information on prior consultation with NIAID program staff, refer to the NIAID Standard Operating Procedure for Investigator Initiated Clinical Trial Planning and Implementation Awards.
NIAID reserves the right to provide support for clinical trials through other available mechanisms supported by NIAID. If NIAID ascertains that substantial additional planning may be necessary, or that substantial staff involvement may not be necessary, the applicant will be encouraged to consider funding under the Clinical Trial Planning Grant (R34) (PAR-20-270) or Parent (R01 Clinical Trial Required) FOA (PA-20-183), Parent (R21 Clinical Trial Required) FOA (PA-20-194) respectively.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
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.
Significance
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Investigator(s)
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Innovation
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 design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
Does the application adequately address the following, if applicable:
Study Design
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Specific to this FOA: Is the project plan realistic to allow for completion of the study and obtaining scientifically and clinically relevant final report within the period of the award? Does the application adequately describe plans to implement and monitor Good Clinical Practices (GCP), Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP), as applicable. Does the application adequately describe compliance with regulatory requirements? Are the consent and data collection forms, sites, pharmacies, labs, brochures, and MOPs appropriate? Do the Informed Consent Forms cover required elements and provide adequate information to the participant to make an informed decision? Is the protocol complete and sufficiently detailed to allow for immediate implementation? Is the safety monitoring plan commensurate with the risks of the trial, its size and complexity?
Environment
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?
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
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.
Study Timeline
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
Milestones
Are the proposed milestones feasible and well justified?
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the 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.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
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.
Resubmissions
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.
Renewals
Not Applicable
Revisions
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.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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.
Applications from Foreign Organizations
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.
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) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
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 National Institute of Allergy and Infectious Diseases, 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 will receive a written critique.
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.
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. 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:
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain "applicable clinical trials" on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
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.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
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 Part 75, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the 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:
An NIAID Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Areas of Joint Responsibility include:
A Steering Committee (SC), if applicable, will have responsibility for facilitating the conduct of the studies. Awardees will be required to accept and implement the common protocol and procedures approved by the SC. The SC should meet with monthly.
Each member will have one vote. Awardees will be required to accept and implement policies approved by the Steering Committee.
Additional details and responsibilities of the Steering Committee will be negotiated at the time of award or post-award.
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 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.
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
A final RPPR, 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.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-637-3015
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Martin Gutierrez
Division of AIDS (DAIDS)
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-4844
Email: [email protected]
Ellen Goldmuntz, M.D., Ph.D.
Division of Allergy, Immunology and Transplantation (DAIT)
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3502
Email: [email protected]
DMID IICT Central Contact Mailbox
Division of Microbiology and Infectious Diseases (DMID)
National Institute of Allergy and Infectious Diseases (NIAID)
[email protected]
Louis Rosenthal, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5070
Email: [email protected]
Regina Kitsoulis
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2946
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 Part 75.