Notice of Change to IND/IDE Authorization Timing Requirement for PAR-18-407 "Clinical Coordinating Center for Multi-Site Investigator-Initiated Clinical Trials (Collaborative UG3/UH3 Clinical Trial Required)"

Notice Number: NOT-HL-18-626

Key Dates
Release Date:   May 9, 2018

Related Announcements
PAR-18-407

Issued by
National Heart, Lung, and Blood Institute (NHLBI)

Purpose

The purpose of this Notice is to inform potential applicants of a revision to the IND/IDE authorization timing requirement for PAR-18-407, "Clinical Coordinating Center for Multi-Site Investigator-Initiated Clinical Trials (Collaborative UG3/UH3 Clinical Trial Required)". Beginning with the June 13, 2018 application due date, all necessary regulatory approvals must be obtained and provided to NHLBI before the award will be made.

The following sections of PAR-18-407 have been modified (shown in bold-italics).

Section I. Funding Opportunity Description

CURRENT LANGUAGE

Phases of Award
The UG3 phase will support the development of case report forms and other resources necessary to the performance of the trial; further development of study partnerships; finalization and Institutional Review Board/Data and Safety Monitoring Board approval of the trial protocol, informed consent(s), manual of operations, and clinical trial project management plans. Applications that address a comprehensive clinical trial project management plan that includes consideration of feasibility of trial launch, conduct, and completion, and also on-time and on-budget performance milestones are strongly encouraged. All necessary regulatory approvals, as well as provision of the necessary drugs, devices or other resources, should be obtained by the end of the UG3 award to allow for the successful launch and execution of the proposed clinical trial in the UH3 phase. In addition, it is expected that enrollment into the clinical trial will begin by the end of the UG3 phase or sooner. Subject to NHLBI funding availability and scientific priorities, UH3 awards will be made after administrative review with specific attention to the extent to which agreed-upon milestones have been met. If the UH3 is funded, an additional administrative review will be scheduled within the first two years of the UH3 to assess progress toward UH3 milestones or enrollment milestones. 

REVISED LANGUAGE

Phases of Award
The UG3 phase will support the development of case report forms and other resources necessary to the performance of the trial; further development of study partnerships; finalization and Institutional Review Board/Data and Safety Monitoring Board approval of the trial protocol, informed consent(s), manual of operations, and clinical trial project management plans. Applications that address a comprehensive clinical trial project management plan that includes consideration of feasibility of trial launch, conduct, and completion, and also on-time and on-budget performance milestones are strongly encouraged.

For trials using an FDA regulated product and requiring an IND or IDE application to administer the product to humans, investigators must (1) secure IND authorization or IDE approval and (2) provide documentation of this authorization or approval to NHLBI before the NHLBI award will be made. All necessary regulatory approvals must be provided to NHLBI before any award will be made. Necessary drugs, devices, or other resources must be obtained by the end of the UG3 award to allow for the successful launch and execution of the proposed clinical trial in the UH3 phase.

In addition, it is expected that enrollment into the clinical trial will begin by the end of the UG3 phase or sooner. Subject to NHLBI funding availability and scientific priorities, UH3 awards will be made after administrative review with specific attention to the extent to which agreed-upon milestones have been met. If the UH3 is funded, an additional administrative review will be scheduled within the first two years of the UH3 to assess progress toward UH3 milestones or enrollment milestones. 

Section IV. Application and Submission Information

CURRENT LANGUAGE

2.7 Study Timeline

The milestone plan should include key milestones that need to be met during the UG3 phase to allow for successful launch of the full trial in the UH3 phase of the clinical trial. The overall enrollment and site participation expected by the end of the UG3 phase will be agreed upon between the investigators and the NHLBI prior to an award. It is generally expected that at least one participant will be enrolled by the end of the UG3 phase as well as about 25% of participating sites activated so that accrual targets can be met on time during the UH3 phase. The milestone plan also needs to describe the milestones that need to be reached in the UH3 phase to address the specific aims and ensure the successful completion of the clinical trial and dissemination of its results. Investigators and NHLBI will review and mutually agree upon a final revised milestone plan that will be included in the Terms and Conditions of the grant (if awarded). CCC milestones of particular interest during the UG3/UH3 phases should include but are not limited to:

  • Complete finalized clinical protocol
  • Finalize informed consent(s) and, if applicable, assent forms
  • Agreements in place for product supply (if applicable)
  • Comprehensive laboratory plan
  • Pharmacy/Laboratories Identification (as applicable)
  • Contracts/Third Party Agreements (if applicable)
  • Training of sites
  • Final Management/Communication Plan
  • Final Data and Safety Monitoring Plan
  • Site Performance Plan
  • Data Completeness and Quality Monitoring Reporting Plan
  • Completion of regulatory approvals
  • 25% of sites activated
  • Enrollment of the first subject during the UG3 period  
  • UG3/UH3 transition meeting
  • Enrollment of 25%, 50%, 75% and 100% of the projected recruitment for all study participants, including women, minorities and children (as appropriate)
  • Assessment of site(s) protocol implementation performance
  • Collection of data related to primary and secondary endpoints and database lock
  • Submission of primary manuscript to peer-reviewed scientific journal(s) and dissemination of results
  • Submission of study results to ClinicalTrials.gov within 12 months of the primary completion date

 

REVISED LANGUAGE
NOTE: Because all regulatory approvals must now be obtained and provided to NHLBI before any award will be made, the "Completion of regulatory approvals" milestone bullet has been deleted from Section 2.7 of PAR-18-407 as shown below.

2.7 Study Timeline

The milestone plan should include key milestones that need to be met during the UG3 phase to allow for successful launch of the full trial in the UH3 phase of the clinical trial. The overall enrollment and site participation expected by the end of the UG3 phase will be agreed upon between the investigators and the NHLBI prior to an award. It is generally expected that at least one participant will be enrolled by the end of the UG3 phase as well as about 25% of participating sites activated so that accrual targets can be met on time during the UH3 phase. The milestone plan also needs to describe the milestones that need to be reached in the UH3 phase to address the specific aims and ensure the successful completion of the clinical trial and dissemination of its results. Investigators and NHLBI will review and mutually agree upon a final revised milestone plan that will be included in the Terms and Conditions of the grant (if awarded). CCC milestones of particular interest during the UG3/UH3 phases should include but are not limited to:

  • Complete finalized clinical protocol
  • Finalize informed consent(s) and, if applicable, assent forms
  • Agreements in place for product supply (if applicable)
  • Comprehensive laboratory plan
  • Pharmacy/Laboratories Identification (as applicable)
  • Contracts/Third Party Agreements (if applicable)
  • Training of sites
  • Final Management/Communication Plan
  • Final Data and Safety Monitoring Plan
  • Site Performance Plan
  • Data Completeness and Quality Monitoring Reporting Plan
  • 25% of sites activated
  • Enrollment of the first subject during the UG3 period  
  • UG3/UH3 transition meeting
  • Enrollment of 25%, 50%, 75% and 100% of the projected recruitment for all study participants, including women, minorities and children (as appropriate)
  • Assessment of site(s) protocol implementation performance
  • Collection of data related to primary and secondary endpoints and database lock
  • Submission of primary manuscript to peer-reviewed scientific journal(s) and dissemination of results
  • Submission of study results to ClinicalTrials.gov within 12 months of the primary completion date

 

Section IV. Application and Submission Information

CURRENT LANGUAGE

4.6 Will the study use an FDA-regulated intervention?

4.6.a If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status:

Provide evidence of prior communications (letters/emails) and/or the outcomes pre-IND or pre-IDE meeting, with the FDA. If the protocol is exempt from an IND/IDE and, if available, provide a copy of the exemption letter from the FDA.

If communication has not yet been established, describe the process that will be used for attaining all necessary FDA or other applicable regulatory agency approvals necessary for the conduct of the trial and associated timeline. If the protocol is conducted under a non-US regulatory agency, a plan for attaining applicable regulatory approvals should be provided.

REVISED LANGUAGE

4.6 Will the study use an FDA-regulated intervention?

4.6.a If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status:

If the protocol is exempt from an IND or IDE, applicants are required to provide a copy of the exemption letter from the FDA. If the protocol is conducted under a non-US regulatory agency, equivalent documentation must be provided to NHLBI before the award will be made.

CURRENT LANGUAGE (IN PART):

Section VI. Award Administration Information

For trials using an FDA regulated product and requiring an IND or IDE application, the IND application or IDE application must be submitted to the FDA more than 30 days prior to when a grant award would be expected to be made so that documentation of the FDA determination regarding the application is available to NHLBI prior to a possible award. If the protocol is conducted under a non-US regulatory agency, equivalent determinations must be provided to NHLBI prior to award.

REVISED LANGUAGE (IN PART):

Section VI. Award Administration Information

For trials using an FDA regulated product and requiring an IND or IDE application to administer the product to humans, investigators must (1) secure IND authorization or IDE approval and (2) provide documentation of this authorization or approval to NHLBI before the award will be made. If the protocol is exempt from an IND or IDE, applicants are required to provide a copy of the exemption letter from the FDA. If the protocol is conducted under a non-US regulatory agency, equivalent documentation must be provided to NHLBI before the award will be made.

All other aspects of this FOA remain unchanged.

Inquiries

Please direct all inquiries to:

Anthony Agresti 
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8014
Email: 
agrestia@nhlbi.nih.gov