Neurological Devices and IDE Considerations: New FDA Guidance
The FDA Center for Devices and Radiological Health (CDRH) released new guidance on November 7, 2016, detailing considerations—related to protocol development, submissions to the FDA, informed consent, and labeling—for researchers preparing to submit an investigational device exemption (IDE) to conduct neurological device clinical investigations.
Neurological devices are generally considered to be significant risk devices by the FDA, and they are used to diagnose, prevent, and treat neurological disorders and conditions, including Alzheimer’s disease, Parkinson’s disease, and epilepsy.
The FDA acknowledges the enormous impact neurological devices can have on populations afflicted with devastating neurological disease and conditions. In addition, it calls out the related significance of research in this area while simultaneously describing scientific advances and the FDA expectations to promote and facilitate reasonably safe neurological devices to market. Given the nature of neurological devices, the FDA takes measures to address the difficulties associated with implementing clinical research in this area.
Protocol Safety Assessments and Trial Design
The new guidance defines and recommends the use of intermediate endpoints, surrogate endpoints, and biomarker tests during device evaluation to contribute to device development, regulatory evaluation, and enhanced assessment of risks and benefits. The FDA notes the identification of appropriate metrics on a short time scale is difficult, given they do not always correlate with disease progression or clinically meaningful benefits. However, careful consideration should be given to the endpoints, biomarkers, and outcome assessments selected, and they should be substantiated as clinically meaningful to the specific population and disease condition.
Of note, the Medical Device Development Tools (MDDT) program may be used by medical device sponsors to qualify biomarker tests in the development and evaluation of medical devices.
The guidance also outlines helpful information the FDA expects to be provided in the IDE application and clinical studies to ensure a complete investigational plan as it relates to evaluation of the device and identification of safety and other risk considerations, such as:
- The IDE application includes a written overview describing all anticipated phases of the clinical investigation. This includes the initial feasibility study with defined clinical metrics or device design, pivotal study stages, and an overview of later phase studies if being planned at the time of submission.
- Clinical studies clearly identify the proposed indications for use (target population), study type and design (e.g., best medical management, delayed-to-treatment in the control arm in comparison to active treatment), and primary safety and effectiveness endpoints described as specific objective clinical targets. The FDA recommends the intervals for evaluating participants be planned to distinguish between symptomatic and disease progression effects.
Note that the FDA provides guidance for making benefit-risk determinations of medical device submissions seeking premarket approval or de novo classification. Importantly, the assessment of benefits and risks does not necessarily have to be made in comparison to the most technologically sophisticated alternative treatment options, but rather to commonly used therapies and treatments.
The FDA further provides it may be appropriate to approve an IDE application when only a subset of the eligible study population identified would be willing to accept the risks associated with the clinical investigation when weighed against the benefits, when enough information is provided to participants to make an informed decision.
Highlighted in the document is the importance of adequately informing participants the research may have little or no effect upon stopping or delaying the progression of their disease, or may even increase the rate of progression. The informed consent should also describe options for discontinuing study participation and the potential need for long-term follow up in order to evaluate the treatment effect.
Finally, the guidance highlights the labeling for neurological devices should target disease populations that may substantially benefit from using the device. Early onset disease populations may present one population of candidates to study disease progression and its impact on patients in identifying target disease populations. Warnings should include:
- Outcomes associated with misuse of the device
- Lack of clinical benefit
- Actions that can be taken to avoid potential injury
Research to develop new and improved treatments for neurological disease is critically important, but presents challenges given the nature of the neurological devices. Due to the complex regulatory and clinical landscape surrounding neurological devices, the FDA strongly recommends sponsors seeking to conduct clinical investigations of neurological devices take advantage of the Pre-Submission Program to streamline the trial design and review process.