NIH – NHLBI Early Phase Clinical Trials for Therapeutics and/or Diagnostics (R61/R33, R33 Clinical Trial Required)

March 5, 2018 by School of Medicine Webmaster

The following description was taken from the R61/R33 version of this FOA.  Offerors who do not require pre-clinical or trial readiness activities should apply directly for an R33.

This FOA is intended to support the development and implementation of Phase I investigator-initiated single or multisite clinical trials for therapeutic and/or diagnostic interventions for heart, lung, blood, and sleep (HLBS) disorders in adults and children. NHLBI seeks applications that propose to contribute to the evidence base for important health matters of relevance to the research mission of NHLBI and which meet the NIH definition of a clinical trial (see NOT -OD-15-015). For additional information about the mission, strategic vision, and research priorities of the NHLBI, applicants are encouraged to consult the NHLBI website: http://www.nhlbi.nih.gov. In addition to scientific relevance and excellence, these clinical trials are expected to be conducted with a high degree of efficiency and with streamlined administrative procedures wherever possible.

This FOA is applicable to single or multisite clinical trials that are Phase I including bridging studies. For the purposes of this FOA, the definition of a bridging study is a study performed to provide clinical data that allows extrapolation of the existing data from the population approved to receive the therapeutic or diagnostic into a new population (e.g., from adult subjects into pediatric subjects).

Structure

This FOA will utilize a bi-phasic, milestone-driven R61/R33 mechanism consisting of a start-up phase (R61) and a clinical trial execution phase (R33). Applicants must address objectives for both a R61 and a R33 phase and are strongly encouraged to use project management principles as appropriate.

Phases of Award

The R61 phase can be up to two years and will support late-stage product development activities required to allow the therapeutic or diagnostic to be administered to humans.  Examples of activities that will be allowed include: stability studies, final formulation studies, establishment of shipping and receiving protocols, Investigational New Drug (IND) filing, and Phase 0 clinical trials. The R61 phase will also support finalization of the protocol and the informed consent/assent document; the development of the manual of operations, case report forms and other resources necessary to the performance of the protocol; further development of study partnerships; 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 to allow for the successful launch of the proposed clinical trial in the R33 phase. An administrative review of the extent to which peer-reviewed milestones are met in the R61 phase will determine whether the R33 phase award will be issued, subject to NHLBI funding availability.  In addition to the primary aim of assessing the safety of the therapeutic/diagnostic product, secondary aims in the R33 phase may include: 1) further testing of the intervention’s feasibility, safety, and acceptability; 2) determining the optimal dose for a subsequent trial by assessing dose-response with respect to a functional pharmacodynamic readout of the biological signature in response to multiple doses of the product; 3) determining the pharmacokinetics of the dose and formulation of the product to be used in future trials to justify the frequency of dosing; and 4) developing functional biological signature measures and clinical outcome measures feasible for use in larger efficacy and effectiveness trials. The specific activities appropriate for the R33 phase will depend on the product under study and available preliminary data on the product.

Milestones

Delineation of milestones by the applicant for the R61 and R33 phases is a key characteristic of this FOA. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity. This FOA will support applications that propose a series of milestones including manufacturing and product development goals in the R61 phase and trial conduct in the R33 phase.  Applicants are expected to complete the trial on time and on budget.  Applications that address contingency plans to proactively confront potential delays in meeting the milestones are strongly encouraged.

Satisfactory completion of R61 milestones will be assessed administratively by NHLBI to determine eligibility to transition to the R33 phase; this includes completion and analysis of any Phase 0 clinical trials.  With the entirety of the Phase I clinical trial in the R33 phase, there will be additional administrative review of accrual milestones within this phase. It is expected that the performance of critical milestones such as expected enrollment goals will be shared on a regular basis through an NHLBI clinical dashboard database.

Additional NHLBI policies relevant to clinical research are the NHLBI Policy for Inclusion of Women and Minorities in Clinical Research, and the  NHLBI Policy for Data and Safety Monitoring of Extramural Clinical Studies.

Clinical Trials Not Supported by this FOA

The following types of clinical trials are not intended to be supported by this FOA:

  • Phase II or III trials (See PAR-18-406PAR-18-407, or PAR-18-410)
  • Observational studies that do not meet the NIH definition of a clinical trial
  • Trials designed to address hypotheses related to the biology and pathobiology of health and/or disease

Specific Areas of Research Interest

Investigators are strongly encouraged to consult with the Scientific/Research Contacts for the area of science for which they are planning to develop an application prior to submitting an application. Early contact (at least 12 weeks prior to submission) is encouraged. This period of time provides an opportunity for NHLBI staff to discuss the scope and goals, and to provide information and guidance to the applicants

Deadlines:  June 4, 2018; October 2, 2018; June 4, 2019; October 2, 2019; June 4, 2020; October 2, 2020 (letters of intent due 30 days prior to the deadline)

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Filed Under: Funding Opportunities