Notice of Change to IND/IDE Authorization Timing Requirement for PAR-18-406 "Single-Site Investigator-Initiated Clinical Trials (R61/R33 Clinical Trial Required)"

Notice Number: NOT-HL-18-625

Key Dates
Release Date:  May 9, 2018

Related Announcements
PAR-18-406

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-18-406, "Single-Site Investigator-Initiated Clinical Trials (R61/R33 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-18-406 have been modified (in bold-italics).

Section I. Funding Opportunity Description

CURRENT LANGUAGE

Phases of Award
The R61 phase will support finalization of the protocol and the informed consent/assent document; the development of the manual of operations and procedures (MOP), case report forms and other resources necessary to the performance of the protocol; further development of study partnerships; establishment of a Data and Safety Monitoring Board and review of the protocol; and Institutional Review Board approval of the trial. All necessary regulatory approvals, as well as source(s) of the necessary drugs, devices or other resources as needed, should be obtained in the R61 phase to allow for the successful launch of the proposed clinical trial in the R33 phase. Enrollment into the clinical trial is expected to begin before the end of the R61 phase to optimize the probability of successfully completing the trial on time and on budget. An administrative review of the extent to which peer-reviewed milestones (including enrollment milestones) are met in the R61 phase will determine whether the R33 phase award will be issued, subject to NHLBI funding availability.

REVISED LANGUAGE

Phases of Award
The R61 phase will support finalization of the protocol and the informed consent/assent document; the development of the manual of operations and procedures (MOP), case report forms and other resources necessary to the performance of the protocol; further development of study partnerships; establishment of a Data and Safety Monitoring Board and review of the protocol; and Institutional Review Board approval of the trial.

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 R61 award to allow for the successful launch and execution of the proposed clinical trial in the R33 phase.

In addition, it is expected that enrollment into the clinical trial will begin by the end of the R61 phase or sooner to optimize the probability of successfully completing the trial on time and on budget. An administrative review of the extent to which peer-reviewed milestones (including enrollment milestones) are met in the R61 phase will determine whether the R33 phase award will be issued, subject to NHLBI funding availability.

Section IV. Application and Submission Information

CURRENT LANGUAGE

2.7 Study Timeline

Enrollment into the clinical trial is expected to begin in the R61 phase to allow for an evaluation of early enrollment and the probability of successfully completing the trial on time and on budget. Near the end of the R61 phase, NHLBI will conduct an administrative review of the extent to which milestones (including enrollment milestones) have been met.  If trial performance is deemed to be sufficient, the R33 phase of the award will be issued, subject to NHLBI funding availability.
The milestone plan must also describe the milestones that need to be reached in the R33 phase to address the specific aims and ensure the successful completion of the clinical trial and dissemination of its results.

  • Milestones of particular interest during the R61 phase may include but are not limited to:
  • Complete finalized study protocol
  • Final Informed consent(s) and, if applicable, assent form(s)
  • Agreements in place for product supply (if applicable)
  • Comprehensive laboratory plan (if applicable)
  • Pharmacy/Laboratories Identification (as applicable)
  • Contracts/Third Party Agreements (if applicable)
  • Training of study staff
  • Final Management/Communication Plan
  • Final IRB-approved Data and Safety Monitoring Plan
  • Site Performance Plan
  • Data Completeness and Quality Monitoring Reporting Plan
  • Completion of regulatory approvals (if applicable)
  • Enrollment of the first subject
  • Submission of data and reports to convey readiness for transition to R33 phase

 

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 (if applicable)" milestone bullet has been deleted from Section 2.7 of PAR-18-406

2.7 Study Timeline

Enrollment into the clinical trial is expected to begin in the R61 phase to allow for an evaluation of early enrollment and the probability of successfully completing the trial on time and on budget. Near the end of the R61 phase, NHLBI will conduct an administrative review of the extent to which milestones (including enrollment milestones) have been met.  If trial performance is deemed to be sufficient, the R33 phase of the award will be issued, subject to NHLBI funding availability.
The milestone plan must also describe the milestones that need to be reached in the R33 phase to address the specific aims and ensure the successful completion of the clinical trial and dissemination of its results.

  • Milestones of particular interest during the R61 phase may include but are not limited to:
  • Complete finalized study protocol
  • Final Informed consent(s) and, if applicable, assent form(s)
  • Agreements in place for product supply (if applicable)
  • Comprehensive laboratory plan (if applicable)
  • Pharmacy/Laboratories Identification (as applicable)
  • Contracts/Third Party Agreements (if applicable)
  • Training of study staff
  • Final Management/Communication Plan
  • Final IRB-approved Data and Safety Monitoring Plan
  • Site Performance Plan
  • Data Completeness and Quality Monitoring Reporting Plan
  • Completion of regulatory approvals (if applicable)
  • Enrollment of the first subject
  • Submission of data and reports to convey readiness for transition to R33 phase

 

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.

Section VI. Award Administration Information

The following paragraphs have been added to this section.

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.

If progress is deemed satisfactory in the first phase, milestones and timelines for the second phase (execution of the trial) may stay the same as originally agreed upon. In certain cases, the milestones and timelines may need to be revised and finalized prior to transitioning into the second phase of the award.  If revision of the milestone plan is needed, investigators and NHLBI staff will review and mutually agree upon a revised milestone plan for the second phase of the trial.

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