See the Glossary for more terms.
Table of Contents
Read the questions and answers below or see the Table of Contents above.
NIAID's investigator-initiated clinical trial implementation U01 is a cooperative agreement for implementing a high-risk clinical trial. Applications must include project milestones, and NIAID staff have substantial scientific involvement during the award.
The U01 is for projects that are high risk, which we define as follows:
For studies that are not high-risk, applicants may apply for a clinical trial implementation R01. For more information, read the Investigator-Initiated Clinical Trial R01 Implementation Grants questions and answers.
If for other reasons we determine that substantial staff involvement is necessary, we may ask you to apply for a U01.
Implementation refers to activities related to the conduct of the clinical trial such as:
Yes. We define a milestone as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. Read the NIAID Clinical Trial Implementation Cooperative Agreement (U01)Guide announcement for information about the milestone plan.
Your application must describe a series of milestones for completing the clinical trial and contingency plans should there be delays. Milestones will be peer reviewed, negotiated with NIAID, and become part of the terms of award. See How do I comply with requirements for human subjects? below.
If the clinical trial you propose is not high risk, apply for an R01. If the clinical trial is high risk, apply for a clinical trial implementation U01. For NIAID's definition of risk, see What is a clinical trial U01 implementation cooperative agreement?
No. However, you must have ready all the documentation you would have prepared during an R34 clinical trial planning grant.
NIAID staff will monitor progress toward meeting your milestones during your annual progress review. They will also oversee the management and reporting of adverse events and have regular communications with you and your study team.
Yes. PIs will benefit from the involvement of NIAID staff. Also, NIAID program staff may be able to help you access Institute-funded resources, for example, those in existing networks, facilities, and laboratories.
Here are the points to consider:
Follow the instructions in the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement. Don't put anything in the Appendix that belongs in the Research Strategy to circumvent the page limits.
Yes. NIAID Clinical Terms of Award will be part of the terms and conditions of award. See the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement for additional terms and conditions of award, which will be modified for each cooperative agreement.
No. Randomization is required only if it is an appropriate element of trial design.
NIAID can hold the IND. Other arrangements are possible; please discuss them with the appropriate NIAID program staff.
Yes, in one of these situations:
In all cases, you must speak to the NIAID point of contact listed on the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement to confirm.
Treatment or prophylaxis is not a clinical trial if subjects are receiving medical treatment or prophylaxis according to standard intervention or the best judgment of their treating physician. If you can obtain the samples you need with less than high risk to the subjects, an R01 application is appropriate.
Make sure your application clearly states that the treating physician is independent of the research proposal. For further advice, discuss your project with the NIAID point of contact listed in the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement.
Yes, as long as providing samples for your studies represents minimal additional risk to the clinical trial subjects. You should explicitly state that you are not requesting support for the clinical trial. You will need to provide documentation that the clinical trial sponsor is aware of your proposal and will provide necessary access to the samples.
For additional advice, discuss your project with the NIAID point of contact listed in the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement.
Each application has unique circumstances, so we will decide on a case-by-case basis. For help, call the NIAID point of contact listed in the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement.
You may also wish to read Are there circumstances where the investigator-initiated clinical trials process is not required or appropriate?
Discuss your project with the NIAID point of contact listed in the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement.
Go to the Investigator-Initiated Clinical Trial Resources main page for resources, and contact staff listed in the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement.
No. We do strongly encourage you to request a prior consultation with NIAID staff, though. Learn more in the Investigator-Initiated Clinical Trial Planning and Implementation Awards SOP.
Follow these steps:
In your cover letter, you will identify the staff member who agreed to accept assignment of the application to NIAID and attach the prior consultation summary letter from the division director.
See Requesting Prior Consultation to Discuss Submission of a Clinical Trial Planning (R34) or Implementation (R01 or U01) Application and the questions below for details.
Yes, the limit is five pages.
A program officer will send you a letter signed by the NIAID division director that summarizes the prior consultation, which you will include with your U01 application.
NIAID will provide a prior consultation summary letter within six weeks after the consultation.
No, you may submit more than one application provided each is scientifically distinct.
No, each U01 application will support the implementation of one clinical trial.
Request resources and time appropriate to complete the clinical trial. You may request up to five years of support.
If you are requesting a budget over $500,000 in direct costs in any one year, include a section for approval of a big grant application in your request for prior consultation.
Although a large budget requires approval, we will handle both requests together. Read the Investigator-Initiated Clinical Trial Planning and Implementation Awards SOP for details.
Yes, if you follow procedures for a multiple PI application.
Go to these NIAID resources:
Contact the appropriate NIAID point of contact in the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement for division-specific procedures.
Read the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement for instructions.
Here is an overview of the key elements of what you include in a U01 application:
Attach a PDF file in the PHS 398 Cover Letter File of the grant application package.
Your Research Plan is limited to one page for the Specific Aims, 12 pages for the Research Strategy.
The following three sections comprise the Research Strategy: Significance, Innovation, and Approach. In addition, the Research Strategy may not exceed 12 pages and must include:
What do I have to include in my application to ensure it's responsive?
You must include an appropriate Clinical Protocol Synopsis, Statistical Analysis Plan, Data Safety and Monitoring Plan, Milestone Plan, and Complete Clinical Protocol.
If your application omits any of these components in the SF 424 Application Other Project Information Form under the section entitled "Other Attachments," it will be considered nonresponsive and will not be reviewed. Read the NIAID Clinical Trial Implementation Cooperative Agreement (U01) for full instructions.
Closely follow the instructions in the PHS 398 Part II Supplemental Instructions for Preparing the Protection of Human Subjects Section of the Research Plan and the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement.
Clinical Protocol Synopsis
The Clinical Protocol Synopsis should be included at the end of the Human Subjects section. Applications that lack the Clinical Protocol Synopsis will not be peer reviewed. The Clinical Protocol Synopsis may not exceed three pages and must include the following information:
Data and Safety Monitoring Plan
A Data and Safety Monitoring (DSM) Plan that is commensurate with the risk level of the proposed clinical research must be included for all clinical trials—see the NIH Policies and IC Guidance for Data and Safety Monitoring of Clinical Trials portal.
All applications or study protocols must include a general description of the monitoring plan, policies, procedures, responsible entities, and approaches to identifying, managing, and reporting reportable events (adverse events and unanticipated problems), to the applicable regulatory agencies, e.g., institutional review board, NIAID, NIH Office of Biotechnology Activities (if appropriate), Office of Human Research Protections, FDA, and any data and safety monitoring board.
The DSM Plan must address the following areas:
Milestone Plan and Complete Clinical Protocol
A Milestone Plan and Complete Clinical Protocol must be included as a single PDF attachment to the Other Project Information component of the SF 424 application.
Complete clinical protocol documents will not count toward the page limit for the Research Plan. Applications that lack the Milestone Plan or complete clinical protocol will not be reviewed.
Applicants must provide detailed project performance and timeline objectives in a section called Milestone Plan. This section may not exceed three pages and must include:
Complete Clinical Protocol
A Complete Clinical Protocol must be included immediately after the Milestone Plan. Please see the Trans NIAID Clinical Research Toolkit for clinical protocol guidance and templates. We urge you to be succinct.
Yes, as applicable:
Prepare a detailed budget. If your application involves multiple institutions, see How do I prepare an application that involves multiple institutions?
Include the following documents in the Appendix material:
Be sure to provide appendix material on CDs.
If you propose research at multiple institutions, designate one institution as the prime institution and the other as a subcontract (subaward) to be administered by the prime institution.
Since you are preparing a detailed budget, the prime institution submits the Research and Related Budget Component forms. Attach the individual budgets for the subawards separately. Follow the instructions in the .
Submit your application electronically using the SF 424 Application Guide. For instructions, see the NIAID Clinical Trial Implementation Cooperative Agreement (U01) Guide announcement.
An NIAID special emphasis panel will peer review it.
Yes, below are the factors added to the standard review criteria. Be aware that your application will also be reviewed for protection of human subjects.
Significance. If proposed, do the mechanistic studies contribute to the understanding of the disease or treatment? Are the study objectives and hypotheses adequately defined?
Investigator(s). Do the PD/PIs and key personnel have the necessary expertise in statistics, data management and study coordination to implement the proposed clinical trial and meet milestones and timelines? Are committee structures appropriate to the complexity of the trial?
For multicenter trials, does the application identify a core of potential center investigators and staffing for a coordinating center? Is the organizational structure of the multicenter trial appropriate?
Innovation. Nothing added.
Environment. -- Does the application adequately address plans to add or drop enrollment centers; the availability of the requisite eligible patient pool; the availability of children, women and minority individuals as trial participants and specific recruitment and retention plans for their inclusion; plans for recruitment outreach and, as appropriate, follow-up procedures to ensure collection of data at stated intervals?
If international sites are proposed, does the application adequately address the complexity of executing the clinical trial?
Innovation. No additional criteria.
Yes, one time. Before resubmitting a revised application, we strongly suggest that you repeat the prior consultation process with the appropriate NIAID program official.
Use the results from the previous review to strengthen your project.
NIAID will not peer review or fund any investigator-initiated clinical trial application that is nonresponsive. We encourage you to contact other NIH institutes to see if they might accept your application.
You may be able to apply for an extension. You can also take a no-cost extension—read more in the No-Cost Extension SOP.
Also see our Investigator-Initiated Clinical Trial Administrative Extensions SOP and Investigator-Initiated Clinical Trial Administrative Extensions questions and answers.
Email email@example.com with the title of this page or its URL and your question or comment. We answer questions by email and post them here. Thanks for helping us clarify and expand our knowledge base.
Last Updated September 16, 2014
Last Reviewed September 16, 2014