This program seeks to encourage the translation of research discoveries into new treatments for neurological disorders and stroke that fall under the National Institute of Neurological Disorders and Stroke (NINDS) mission.
This funding opportunity will utilize a U44 cooperative agreement mechanism to support pre-clinical testing to enable an Investigational Device Exemption (IDE) submission and a subsequent small clinical study (e.g. Early Feasibility Study). For Non-Significant Risk (NSR) clinical studies that do not require an IDE, IRB approval is considered sufficient. This program supports pre-clinical and clinical studies to inform a final device design that would have to go through most, if not all, of the preclinical testing on the path to clinical trials and market approval. This program also supports development of a device to test scientific hypotheses that are not feasible or practical to conduct in animal models, but are critical to enable next-generation devices. Activities that can be supported in this program include implementation of clinical prototype devices, design verification and validation activities, demonstration of preclinical safety and efficacy, pursuit of U.S. regulatory approval for clinical study, and a small clinical study.
Projects must focus on a single disorder that falls within the mission of NINDS. Devices within the scope of this program are expected to require most, if not all, of the in vitro and preclinical animal testing necessary to enable an IDE submission after completion of the Phase II.
For entry to the program, projects should have:
- Comprehensive Supporting Data: Ideally, preliminary proof-of-concept data would be obtained using an in vivo model representative of the intended patient population.
- A compelling case to for a successful IDE submission by the end of Phase I or IRB approval for a Non-Significant Risk (NSR) study at the end of Phase I.
- Overall device development plan, including when contact with the appropriate regulatory bodies is planned, clinical considerations, and a needs assessment.
- Identified one or more clinically meaningful device outcome measures based on input from both clinicians and patients
- Non-binding FDA Pre-Submission (formerly pre-IDE) feedback clearly denoting that the proposed pre-clinical testing plan is sufficient to support a successful FDA submission for an IDE by the end of Phase I. For Non-Significant Risk (NSR) studies, preliminary communications (e.g. letter or other documentation) with the IRB indicating what pre-clinical testing will be necessary to support the NSR clinical study is sufficient.
Examples of studies that can be proposed during the U44 Phase I include, but are not limited to:
- Non-GLP (Good Laboratory Practice) animal studies to develop surgical techniques relevant to the device, define relevant therapeutic parameters, and refine device design in preparation for subsequent GLP testing for regulatory approval
- In vitro and animal testing to meet FDA Recognized ISO/ASTM Standards
- Activities to become GMP (Good Manufacturing Practice) compliant
- Activities to bring the development process under Design and Quality Systems Control
- Device, software, and firmware design verification and validation activities
- Regulatory affairs
- GLP compliant large animal model safety and/or testing of an implanted device
- IDE submission
The U44 Phase II will support a clinical study to inform a final device design, or test scientific hypotheses that are not feasible or practical to conduct in animal models, but are critical to enable next-generation devices. It should be noted that clinical studies are only supported for projects where the preclinical activities are conducted under this funding mechanism.