NIH Director's Transformative Research Award Application & Award Guide

1. SF424 (R&R) Form

Follow all instructions in the SF424 (R&R) Application Guide .

Cover Letter Attachment

Use the Cover Letter Attachment if relevant information needs to be conveyed as outlined in the SF424 (R&R) Application Guide . The cover letter is for internal NIH use only and will not be shared with peer reviewers. Note, applicants are NOT required to have agency approval documentation for budget requests of $500,000 or more because the funding opportunity expressly states that large budgets are welcome.

2. PHS 398 Cover Page Supplement Form

Follow all instructions in the SF424 (R&R) Application Guide .

3. R&R Other Project Information Form

Follow all instructions in the SF424 (R&R) Application Guide .

Other Tips

• For more help on human subjects, visit the NIH Grants & Funding website .
• Foreign components are defined as the performance of any significant scientific element or segment of a project outside of the United States, either by the recipient or by a researcher employed by a foreign organization, whether or not grant funds are expended. It is crucial that you disclose all foreign components, which include foreign collaborations that will result in co-authorship. See the definition of Foreign Components for more details.
• A Project Summary/Abstract must be included. There is a limit of 30 lines of text.
• A Project Narrative must be included. There is a limit of three sentences.

4. Project/Performance Site Location(s)

Follow all instructions in the SF424 (R&R) Application Guide .

5. R&R Senior/Key Person Profile Form

Follow all instructions in the SF424 (R&R) Application Guide .

6. R&R or PHS 398 Modular Budget Form

Follow all instructions in the SF424 (R&R) Application Guide . If the budget request is greater than $250,000 in direct costs per year, use the R&R Budget Form. If the budget request is equal to or less than $250,000 in direct costs per year, use the PHS 398 Modular Budget Form.

7. R&R Subaward Budget Attachment(s) Form

Follow all instructions in the SF424 (R&R) Application Guide .

8. PHS 398 Research Plan Form

Follow all instructions in the SF424 (R&R) Application Guide with additional instructions in the funding opportunity.

Specific Aims

Do not list specific objectives of the proposed research. Instead, describe the overall project and why it is well aligned with the objectives of the Transformative Research Award. The Specific Aims page should include two sections addressing the following questions:

1. Significance, Innovation, and Impact
   • What is the challenge or opportunity that is the focus of your proposed research?
   • Why is this broadly significant?
   • What is the overall approach you are proposing?
   • What are the most innovative aspects of your application?
   • If successful, what would the impact be on our scientific understanding and (ultimately) human health?
2. Insight and Rationale
   • What is the fundamental new insight that is motivating the proposed research?
   • What is the underlying logic or rationale that provides support for pursuing this insight despite little or no preliminary data?

The content of the two sections should be clear and compelling even to those who are not experts in the immediate field of the proposed research.

Research Strategy

The Research Strategy essay must be organized into five sections:

1. Overview of research project
   • Briefly describe what is being proposed and why it is important.
   • Briefly describe what is the state-of-the-art or a major challenge in the broad field of the application and how the proposed project will greatly advance and transform the broad field.
   • State the fundamental new insight that is driving the project.
2. Approach
   • Describe the overall approach to be pursued.
   • Do not include a detailed experimental plan or substantial preliminary data. If limited preliminary data are provided, they will be evaluated. The inclusion of substantial preliminary data is not aligned with the intent of the Transformative Research Award. Prominently state that, per the NOFO instructions, a detailed experimental plan and substantial preliminary data are not being provided.
   • In lieu of preliminary data, provide the underlying logic or rationale for pursuing the project in the manner proposed.
   • Summarize the major challenges or risks in the project and alternate approaches that may need to be pursued.
   • Applicants proposing clinical trials may reference but should not repeat information submitted on the PHS Human Subjects Clinical Trial Information form.
   • Despite the lack of detailed plans and data, the reviewers must still ​​​​​
     1. Have a clear sense of what is being proposed and why it is important.
     2. Be convinced that the applicants have thought very deeply about the project.
     3. Be satisfied that the research will be conducted in a robust, rigorous, and reproducible manner. Thus, when vertebrate animal or human subjects are to be used, this section should include the numbers of subjects to be used and a justification for the numbers. In addition, the use of key biological variables, such as sex, should be addressed.
3. Innovation
   • Describe the elements of exceptional innovation in your proposed research and how they compare to current approaches, paradigms, practices, or perspectives.
4. Appropriateness for the Transformative Research Award
   • Why is the proposed research well suited to the goals of the Transformative Research Award rather than a more traditional research grant program?
5. Timeline
   • Design the project to have deliverables with potential transformative impact by the end of the project period. The project should not be framed as initiating a line of research with potential transformative impact after additional periods of support.
   • Provide a timeline with points indicating where intermediate objectives will be assessed, measurable outcomes that will be used to monitor progress, and the timing and process for reaching decisions regarding the course and direction of continuing the research effort. Given the high degree of risk involved in applications submitted under the Transformative Research Award, it is anticipated that investigators will need to continually reassess approaches based on experimental outcomes and potentially alter course to meet project goals. Possible alternative paths that may be followed at critical junctures in the project plan should be indicated on the timeline.

Components of the Other Research Plan Section

The following components of Research Plan section follow the instructions in the SF424 (R&R) Application Guide :

• Vertebrate Animals
• Select Agent Research
• Multiple PD/PI Leadership Plan
• Consortium/Contractual Arrangements
• Letters of Support
• Resource Sharing Plan(s)
• Other Plan(s)
• Authentication of Key Biological and/or Chemical Reagents

9. PHS Human Subjects and Clinical Trials Information

Follow all instructions in the SF424 (R&R) Application Guide .

Applicants considering clinical trials research are encouraged to discuss their research with the most scientifically relevant NIH Institute or Center (IC) to ensure the research conforms to the IC's clinical trials research policies. Applications must comply with the clinical trials policies of the administering IC in order to be funded. For a list of IC clinical trials staff contacts, visit the HRHR website .

10. PHS Assignment Request Form

Follow all instructions in the SF424 (R&R) Application Guide , but do not request an assignment to a particular review panel (integrated review group) or awarding component (NIH Institute or Center). All applications are automatically received as "Office of the Director" applications and reviewed by a single Special Emphasis Panel convened by the Center for Scientific Review.

If you wish to exclude individuals from reviewing your application, list their names, institutional affiliations, and the reasons why they should not serve as reviewers. NIH will consider this request but is not obligated to accept it.

1. SF424 (R&R) Form

Follow all instructions in the SF424 (R&R) Application Guide .

Cover Letter Attachment

Use the Cover Letter Attachment if relevant information needs to be conveyed as outlined in the SF424 (R&R) Application Guide . The cover letter is for internal NIH use only and will not be shared with peer reviewers. Note, applicants are NOT required to have agency approval documentation for budget requests of $500,000 or more because the funding opportunity expressly states that large budgets are welcome.

2. PHS 398 Cover Page Supplement Form

Follow all instructions in the SF424 (R&R) Application Guide .

3. R&R Other Project Information Form

Follow all instructions in the SF424 (R&R) Application Guide .

Other Tips

• For more help on human subjects, visit the NIH Grants & Funding website .
• Foreign components are defined as the performance of any significant scientific element or segment of a project outside of the United States, either by the recipient or by a researcher employed by a foreign organization, whether or not grant funds are expended. It is crucial that you disclose all foreign components, which include foreign collaborations that will result in co-authorship. See the definition of Foreign Components for more details.
• A Project Summary/Abstract must be included. There is a limit of 30 lines of text.
• A Project Narrative must be included. There is a limit of three sentences.

4. Project/Performance Site Location(s)

Follow all instructions in the SF424 (R&R) Application Guide .

5. R&R Senior/Key Person Profile Form

Follow all instructions in the SF424 (R&R) Application Guide .

6. R&R or PHS 398 Modular Budget Form

Follow all instructions in the SF424 (R&R) Application Guide . If the budget request is greater than $250,000 in direct costs per year, use the R&R Budget Form. If the budget request is equal to or less than $250,000 in direct costs per year, use the PHS 398 Modular Budget Form.

7. R&R Subaward Budget Attachment(s) Form

Follow all instructions in the SF424 (R&R) Application Guide .

8. PHS 398 Research Plan Form

Follow all instructions in the SF424 (R&R) Application Guide with additional instructions in the funding opportunity.

Specific Aims

Do not list specific objectives of the proposed research. Instead, describe the overall project and why it is well aligned with the objectives of the Transformative Research Award. The Specific Aims page should include two sections addressing the following questions:

1. Significance, Innovation, and Impact
   • What is the challenge or opportunity that is the focus of your proposed research?
   • Why is this broadly significant?
   • What is the overall approach you are proposing?
   • What are the most innovative aspects of your application?
   • If successful, what would the impact be on our scientific understanding and (ultimately) human health?
2. Insight and Rationale
   • What is the fundamental new insight that is motivating the proposed research?
   • What is the underlying logic or rationale that provides support for pursuing this insight despite little or no preliminary data?

The content of the two sections should be clear and compelling even to those who are not experts in the immediate field of the proposed research.

Research Strategy

The Research Strategy essay must be organized into five sections:

1. Overview of research project
   • Briefly describe what is being proposed and why it is important.
   • Briefly describe what is the state-of-the-art or a major challenge in the broad field of the application and how the proposed project will greatly advance and transform the broad field.
   • State the fundamental new insight that is driving the project.
2. Approach
   • Describe the overall approach to be pursued.
   • Do not include a detailed experimental plan or substantial preliminary data. If limited preliminary data are provided, they will be evaluated. The inclusion of substantial preliminary data is not aligned with the intent of the Transformative Research Award. Prominently state that, per the NOFO instructions, a detailed experimental plan and substantial preliminary data are not being provided.
   • In lieu of preliminary data, provide the underlying logic or rationale for pursuing the project in the manner proposed.
   • Summarize the major challenges or risks in the project and alternate approaches that may need to be pursued.
   • Applicants proposing clinical trials may reference but should not repeat information submitted on the PHS Human Subjects Clinical Trial Information form.
   • Despite the lack of detailed plans and data, the reviewers must still ​​​​​
     1. Have a clear sense of what is being proposed and why it is important.
     2. Be convinced that the applicants have thought very deeply about the project.
     3. Be satisfied that the research will be conducted in a robust, rigorous, and reproducible manner. Thus, when vertebrate animal or human subjects are to be used, this section should include the numbers of subjects to be used and a justification for the numbers. In addition, the use of key biological variables, such as sex, should be addressed.
3. Innovation
   • Describe the elements of exceptional innovation in your proposed research and how they compare to current approaches, paradigms, practices, or perspectives.
4. Appropriateness for the Transformative Research Award
   • Why is the proposed research well suited to the goals of the Transformative Research Award rather than a more traditional research grant program?
5. Timeline
   • Design the project to have deliverables with potential transformative impact by the end of the project period. The project should not be framed as initiating a line of research with potential transformative impact after additional periods of support.
   • Provide a timeline with points indicating where intermediate objectives will be assessed, measurable outcomes that will be used to monitor progress, and the timing and process for reaching decisions regarding the course and direction of continuing the research effort. Given the high degree of risk involved in applications submitted under the Transformative Research Award, it is anticipated that investigators will need to continually reassess approaches based on experimental outcomes and potentially alter course to meet project goals. Possible alternative paths that may be followed at critical junctures in the project plan should be indicated on the timeline.

Components of the Other Research Plan Section

The following components of Research Plan section follow the instructions in the SF424 (R&R) Application Guide :

• Vertebrate Animals
• Select Agent Research
• Multiple PD/PI Leadership Plan
• Consortium/Contractual Arrangements
• Letters of Support
• Resource Sharing Plan(s)
• Other Plan(s)
• Authentication of Key Biological and/or Chemical Reagents

9. PHS Human Subjects and Clinical Trials Information

Follow all instructions in the SF424 (R&R) Application Guide .

Applicants considering clinical trials research are encouraged to discuss their research with the most scientifically relevant NIH Institute or Center (IC) to ensure the research conforms to the IC's clinical trials research policies. Applications must comply with the clinical trials policies of the administering IC in order to be funded. For a list of IC clinical trials staff contacts, visit the HRHR website .

10. PHS Assignment Request Form

Follow all instructions in the SF424 (R&R) Application Guide , but do not request an assignment to a particular review panel (integrated review group) or awarding component (NIH Institute or Center). All applications are automatically received as "Office of the Director" applications and reviewed by a single Special Emphasis Panel convened by the Center for Scientific Review.

If you wish to exclude individuals from reviewing your application, list their names, institutional affiliations, and the reasons why they should not serve as reviewers. NIH will consider this request but is not obligated to accept it.

3. APPLICATION SUBMISSION

NIH expects that applications be submitted on time, which means the application is submitted error free no later than 5:00 PM local (applicant institution) time on the application due date. There is no deadline extension to correct for errors in the application, so all errors must be corrected by the submission deadline.

Institutions often have their own internal deadlines, so be sure to check when your institution needs your application.

Phase I

Phase I is conducted by an editorial panel composed of scientists from an array of scientific backgrounds. The composition of the editorial panel attempts to capture a wide breadth of scientific expertise, experiences, and perspectives.

The editorial panel uses the Specific Aims pages to identify a subset of applications with the most transformative potential. The review process ends for the unselected applications, while the subset of selected applications moves on to Phase II.

Phase II

Phase II is conducted by topic experts (also called "mail" reviewers) who are knowledgeable in the application’s subject area and are assigned based on close matching of their expertise to the application topic. Each application will have three topic experts assigned to review it. Each expert will provide comments, which are provided to the editorial panel for Phase III.

Phase III

In Phase III, the editorial panel, informed by the critiques from the topic experts, will select a further subset of applications to be discussed and scored by the panel. All other applications will be designated as "not discussed." Typically, only about 18-20% of the applications are chosen for discussion. Panel members provide preliminary scores and lead a panel discussion of their assigned applications. Following the panel discussion, the applications are scored by the whole panel. All review criteria will be assessed in the scoring by the panel. The panel discussion is captured by the SRO and is summarized in the summary statement.

Scoring & Summary Statement

Each panel member privately scores each discussed application. A raw score of 1 is the best, while 9 is the worst. The SRO collects and averages all the panel scores and multiplies the resulting number by 10 to yield an overall impact score. A discussed application can have an overall impact score of 10 (best) to 90 (worst). The panel has access to the full range of scores to provide discrimination among applications within this select subset. These scores should not be compared to a regular R01 study section review.

After the meeting, all discussed applications will receive an overall impact score within three business days through the PD/PI's eRA Commons account. The overall impact score indicates the reviewers' judgment of the significance of the problem, transformative potential of the project, and the innovativeness of the approach. There is a correlation between a strong impact score and funding. However, there is no strict cutoff or pay line for funding. And because applications are responding to a Request for Applications (RFA), the scores are not percentiled, which makes their interpretation difficult. NIH staff cannot disclose where an impact score falls relative to other application scores.

A summary statement prepared by the SRO will be available within 30 days of the review through the PD/PI's eRA Commons account. The summary statement of discussed applications includes critiques from the Phase II topic experts and a brief summary of the panel discussion. The information provided in the summary statement is valuable and provides critical feedback. However, it is not intended to be an exhaustive critique and will not contain every point reviewers found to be problematic. Applications that made it past Phase I are considered "not discussed" and are given a summary statement with critiques from the mail reviewers. Applications that did not make it through Phase I are given a description of the review process.

After Receiving the Summary Statement

If you have any questions about your Summary Statement, you should reach out to the scientific contact for the Transformative Research Award (listed in the funding opportunity). The scientific contact attends the review and may be able to provide more insight into the panel discussion and help clarify some of the comments. You can also ask about the probability of funding and get advice on what to do if your application is outside of the likely pay range. Contacting NIH staff to “sell” your application or to express differences in scientific opinion related to the reviewers’ comments will not affect the likelihood of funding.

It is best to contact NIH staff by email to schedule a time for a meeting. That gives staff time to read your summary statement and review any notes. And be patient. They will receive numerous inquiries and may not be able to respond to yours immediately.

PD/PIs of discussed applications are given an opportunity to submit an optional two-page response to their summary statement. The response should address issues and concerns brought up by reviewers, but the response will not be seen by reviewers and is not a part of the review. The response remains an internal NIH document used only by NIH staff during funding deliberations. The scientific contact will reach out to eligible applicants directly with more information on the response and the deadline.

Second Level of Review

The Council of Councils performs the second level of review for the Transformative Research Award and assesses the first level of review for fairness and uniformity in the application of review criteria. It is meant to ensure the initial review was conducted with the appropriate expertise, procedures, and without conflicts of interest. The Council of Councils is not tasked with reviewing the applications for scientific or technical merit and is not asked to provide recommendations on which applications should be funded. The Council of Councils votes en bloc for concurrence with the first level review recommendations. Applications must receive approval from the council to be eligible for funding.

Phase I

Phase I is conducted by an editorial panel composed of scientists from an array of scientific backgrounds. The composition of the editorial panel attempts to capture a wide breadth of scientific expertise, experiences, and perspectives.

The editorial panel uses the Specific Aims pages to identify a subset of applications with the most transformative potential. The review process ends for the unselected applications, while the subset of selected applications moves on to Phase II.

Phase II

Phase II is conducted by topic experts (also called "mail" reviewers) who are knowledgeable in the application’s subject area and are assigned based on close matching of their expertise to the application topic. Each application will have three topic experts assigned to review it. Each expert will provide comments, which are provided to the editorial panel for Phase III.

Phase III

In Phase III, the editorial panel, informed by the critiques from the topic experts, will select a further subset of applications to be discussed and scored by the panel. All other applications will be designated as "not discussed." Typically, only about 18-20% of the applications are chosen for discussion. Panel members provide preliminary scores and lead a panel discussion of their assigned applications. Following the panel discussion, the applications are scored by the whole panel. All review criteria will be assessed in the scoring by the panel. The panel discussion is captured by the SRO and is summarized in the summary statement.

Scoring & Summary Statement

Each panel member privately scores each discussed application. A raw score of 1 is the best, while 9 is the worst. The SRO collects and averages all the panel scores and multiplies the resulting number by 10 to yield an overall impact score. A discussed application can have an overall impact score of 10 (best) to 90 (worst). The panel has access to the full range of scores to provide discrimination among applications within this select subset. These scores should not be compared to a regular R01 study section review.

After the meeting, all discussed applications will receive an overall impact score within three business days through the PD/PI's eRA Commons account. The overall impact score indicates the reviewers' judgment of the significance of the problem, transformative potential of the project, and the innovativeness of the approach. There is a correlation between a strong impact score and funding. However, there is no strict cutoff or pay line for funding. And because applications are responding to a Request for Applications (RFA), the scores are not percentiled, which makes their interpretation difficult. NIH staff cannot disclose where an impact score falls relative to other application scores.

A summary statement prepared by the SRO will be available within 30 days of the review through the PD/PI's eRA Commons account. The summary statement of discussed applications includes critiques from the Phase II topic experts and a brief summary of the panel discussion. The information provided in the summary statement is valuable and provides critical feedback. However, it is not intended to be an exhaustive critique and will not contain every point reviewers found to be problematic. Applications that made it past Phase I are considered "not discussed" and are given a summary statement with critiques from the mail reviewers. Applications that did not make it through Phase I are given a description of the review process.

After Receiving the Summary Statement

If you have any questions about your Summary Statement, you should reach out to the scientific contact for the Transformative Research Award (listed in the funding opportunity). The scientific contact attends the review and may be able to provide more insight into the panel discussion and help clarify some of the comments. You can also ask about the probability of funding and get advice on what to do if your application is outside of the likely pay range. Contacting NIH staff to “sell” your application or to express differences in scientific opinion related to the reviewers’ comments will not affect the likelihood of funding.

It is best to contact NIH staff by email to schedule a time for a meeting. That gives staff time to read your summary statement and review any notes. And be patient. They will receive numerous inquiries and may not be able to respond to yours immediately.

PD/PIs of discussed applications are given an opportunity to submit an optional two-page response to their summary statement. The response should address issues and concerns brought up by reviewers, but the response will not be seen by reviewers and is not a part of the review. The response remains an internal NIH document used only by NIH staff during funding deliberations. The scientific contact will reach out to eligible applicants directly with more information on the response and the deadline.

Second Level of Review

The Council of Councils performs the second level of review for the Transformative Research Award and assesses the first level of review for fairness and uniformity in the application of review criteria. It is meant to ensure the initial review was conducted with the appropriate expertise, procedures, and without conflicts of interest. The Council of Councils is not tasked with reviewing the applications for scientific or technical merit and is not asked to provide recommendations on which applications should be funded. The Council of Councils votes en bloc for concurrence with the first level review recommendations. Applications must receive approval from the council to be eligible for funding.

3. PRE-AWARD ACTIVITIES

NIH Staff

• Grants Management Officer (GMO) : The GMO signs the Notice of Award (NoA) and is the NIH official responsible for the business management and other non-programmatic aspects of the award. GMOs ensure that laws, regulations, and administrative policies are followed.
• Grants Management Specialist (GMS) : The GMS works with the GMO on the day-to-day management of the grant. The name and contact information of the GMS assigned to a particular grant appears on the NoA.
• Program Official (PO) : The PO is responsible for the programmatic, scientific, and/or technical aspects of assigned applications and grants. The PO coordinates with grants management on post-award administration.

Recipient Organization Participants

• Authorized Organizational Representative (AOR) : The AOR, also known as Signing Official (SO) in the eRA Commons, is the designated representative of the recipient organization in matters related to the award and its administration. Their signature certifies that the applicant organization will comply and is accountable for all assurances and certifications referenced in the application. This individual's signature further certifies that the applicant organization will be accountable both for the appropriate use of funds awarded and for the performance of the grant-supported project or activities resulting from the application.
• Program Director/ Principal Investigator (PD/PI) : The PD/PI is the individual designated by the applicant organization to have the appropriate level of authority and responsibility to direct the project or program supported by the award. The PI is responsible and accountable to the recipient organization for the proper conduct of the project or program, including the submission of all required reports.

The PD/PI is the core member of the award recipient team responsible for ensuring compliance with the financial and administrative aspects of the award. The PD/PI work closely within the award recipient organization to create and maintain necessary documentation, such as technical and administrative reports, preparing justifications, appropriately acknowledging federal support of research findings in publications, announcements, news programs, and other media, and ensuring compliance with other federal and organizational requirements.

NIH encourages the PD/PI to maintain contact with the NIH program officer with respect to the scientific aspects of the project and the grants management officer concerning the business and administrative aspects of the award.

NIH Staff

• Grants Management Officer (GMO) : The GMO signs the Notice of Award (NoA) and is the NIH official responsible for the business management and other non-programmatic aspects of the award. GMOs ensure that laws, regulations, and administrative policies are followed.
• Grants Management Specialist (GMS) : The GMS works with the GMO on the day-to-day management of the grant. The name and contact information of the GMS assigned to a particular grant appears on the NoA.
• Program Official (PO) : The PO is responsible for the programmatic, scientific, and/or technical aspects of assigned applications and grants. The PO coordinates with grants management on post-award administration.

Recipient Organization Participants

• Authorized Organizational Representative (AOR) : The AOR, also known as Signing Official (SO) in the eRA Commons, is the designated representative of the recipient organization in matters related to the award and its administration. Their signature certifies that the applicant organization will comply and is accountable for all assurances and certifications referenced in the application. This individual's signature further certifies that the applicant organization will be accountable both for the appropriate use of funds awarded and for the performance of the grant-supported project or activities resulting from the application.
• Program Director/ Principal Investigator (PD/PI) : The PD/PI is the individual designated by the applicant organization to have the appropriate level of authority and responsibility to direct the project or program supported by the award. The PI is responsible and accountable to the recipient organization for the proper conduct of the project or program, including the submission of all required reports.

The PD/PI is the core member of the award recipient team responsible for ensuring compliance with the financial and administrative aspects of the award. The PD/PI work closely within the award recipient organization to create and maintain necessary documentation, such as technical and administrative reports, preparing justifications, appropriately acknowledging federal support of research findings in publications, announcements, news programs, and other media, and ensuring compliance with other federal and organizational requirements.

NIH encourages the PD/PI to maintain contact with the NIH program officer with respect to the scientific aspects of the project and the grants management officer concerning the business and administrative aspects of the award.