Notice Number: NOT-HL-18-611

Key Dates
Release Date: March 28, 2018

NOT-HL-16-321 Rescinded
NOT-HL-16-336 Rescinded
NOT-HL-17-518 Rescinded
NOT-HL-17-519 Rescinded
NOT-HL-18-610
PAR-16-037
PAR-18-406
PAR-18-407
PAR-18-410
PAR-18-683
PAR-18-684
PAR-19-328
PA-18-345
PA-19-055

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

Purpose

This Notice is to announce the NHLBI policy regarding the submission of applications that seek to conduct a clinical trial (see the NIH definition of a clinical trial) within the mission of NHLBI. The types of clinical trials addressed in this Notice fall into the following categories: 1) pilot studies, 2) mechanistic clinical trials, 3) phase I (early phase) clinical trials, and 4) phase II and beyond clinical trials. Investigators are strongly advised to contact NHLBI scientific staff prior to submitting an application for a clinical trial to determine which Funding Opportunity Announcement (FOA) will best support the proposed clinical trial research and to obtain other important advice.

1. Pilot Studies

• NHLBI will accept applications for pilot studies that collect data that are critical to finalize the design of a future full-scale clinical trial (phase II and beyond), in response to PAR-18-463 NHLBI Clinical Trial Pilot Studies (R34 Clinical Trial Optional) and its reissues.
• Studies may test the feasibility of novel and efficient (pragmatic) trial designs, as well as determine the feasibility of an intervention, intervention parameters, subject availability, or other information essential to complete the design of a trial.

2. Mechanistic Clinical Trials

• In response to PA-18-345 NIH Research Project Grant (Parent R01 Clinical Trial Required) and its reissues, NHLBI will accept only mechanistic studies that meet the NIH definition of a clinical trial (see NOT-HL-18-610).
• For the purposes of this NHLBI policy, a mechanistic clinical trial is defined as a study designed to understand a biological or behavioral process, the pathophysiology of a disease/condition, or the mechanism of action of an intervention.
• NHLBI recognizes that some of the aims of applications that propose a mechanistic clinical trial may also include exploration of fundamental mechanisms that are a major precursor to, or an iterative element of, a clinical study where the latter design or conduct is predicated at least in part on the results of these basic and early translational research aims. As such, NHLBI recognizes that applications can be "hybrid" meaning that they may include as their aims not only a mechanistic clinical trial but also fundamental basic science research aims. NHLBI will accept such hybrid applications as well as applications solely proposing mechanistic trials in response to PA-18-345 and its reissues.
• While mechanistic clinical trials must address the safety of human subjects and may include assessments of clinical outcomes, the purpose of such trials is not the evaluation of safety, clinical efficacy, and/or clinical management.
• 3. Phase I (Early Phase) Clinical Trials

Investigators planning a phase I (early phase) clinical trial (up to but not including phase II), must submit an application to the following NHLBI FOAs specifically designed for early phase clinical trials:

• PAR-18-683 Diagnostics and Therapeutics Early Phase Clinical Trials (R61/R33-Clinical Trial Required), or its reissues
• PAR-18-684 Diagnostics and Therapeutics Early Phase Clinical Trials (R33-Clinical Trial Required), or its reissues
• Applications with early phase clinical trials will only be accepted by NHLBI via PAR-18-683 and PAR-18-684 or their reissues. The purpose of the early phase trial is to evaluate safety, side effects, best dose, timing, and/or best route of administration for a new treatment or therapy.

• 4. Phase II and Beyond Clinical Trials

Investigators planning a single-site or multi-site Phase II and beyond clinical trial must submit an application to the following NHLBI FOAs specifically designed for phase II and beyond clinical trials:

NHLBI Single-Site Phase II and Beyond Clinical Trials
An investigator submitting a Phase II and beyond clinical trial using a single recruitment site must apply to PAR-18-406 or its reissues.

NHLBI Multi-Site Phase II and Beyond Clinical Trials
An investigator submitting a Phase II and beyond clinical trial with more than one recruitment site must apply to:

• PAR-18-407 Clinical Coordinating Center (CCC) for Multi-Site Clinical Trials (Collaborative UG3/UH3 - Clinical Trial Required) or its reissues
• PAR-18-410 Data Coordinating Center (DCC) for Multi-Site Clinical Trials (Collaborative U24 - Clinical Trial Required) or its reissues

Additional Consideration
NHLBI will continue to accept specific clinical trial applications in response to other FOAs published by NHLBI or FOAs where NHLBI is listed as a participant that allow such clinical trials.

Frequently Asked Questions (FAQs) are available at the following sites:

FAQs - NHLBI Multi-Site Clinical Trials

FAQs - NHLBI Single-Site Clinical Trials

Information on NHLBI Research Support Mechanisms for Clinical Trials is available at:
NHLBI Research Support Mechanisms Guidelines and Descriptions.

Inquiries

Please direct all inquiries to:

Email: NHLBIClinicalTrials@mail.nih.gov