Based on advances in biotechnology and neuroscience, non-invasive neuromodulation devices are poised to gain clinical importance in the coming years and to be of increasing interest to patients, clinicians, health systems, payers, and industry. Evidence suggests that both therapeutic and non-therapeutic applications of non-invasive neuromodulation will continue to expand in coming years, particularly for indications where treatments are currently insufficient, such as drug-resistant depression.
Given the growing interest in non-invasive neuromodulation technologies, the Institute of Medicine’s Forum on Neuroscience and Nervous System Disorders convened a workshop, inviting a range of stakeholders—including developers of devices and new technologies, researchers, clinicians, ethicists, regulators, and payers—to explore the opportunities, challenges, and ethical questions surrounding the development, regulation, and reimbursement of these devices for the treatment of nervous system disorders as well as for non-therapeutic uses, including cognitive and functional enhancement (see Box 1-1).
Three non-invasive neuromodulatory devices are currently cleared for the treatment of depression and several others for the treatment of migraines, and many more devices and conditions are being explored.
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1The planning committee’s role was limited to planning the workshop, and the workshop summary has been prepared by the workshop rapporteurs as a factual summary of what occurred at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants, and are not necessarily endorsed or verified by the Institute of Medicine, and they should not be construed as reflecting any group consensus.
There is also a proliferation of over-the-counter (OTC) and do-it-yourself (DIY) device usage. Yet the neuromodulation field also faces significant business-related challenges, including a lack of clarity about how to navigate through regulatory and reimbursement environments to bring a device to market successfully, according to Jeffrey Nye, vice president of Neuroscience Innovation and Scientific Partnership Strategy at Janssen Research & Development, LLC, Johnson & Johnson Innovation. By contrast, he said the pharmaceutical industry has a much more well-developed understanding of these issues. Another hindrance for companies developing therapeutic neuromodulatory devices is that these organizations are typically small relative to those developing drug therapies, and therefore they may have fewer resources to devote to the pursuit of endorsement by regulators and payers, said Ana Maiques, chief executive officer of Neuroelectrics.
Non-invasive neuromodulation is not likely to provide a “magic bullet” for the treatment of conditions such as depression, said Thomas Insel, director of the National Institute of Mental Health (NIMH). He surmised that in the future, device companies may join with pharmaceutical companies to produce combined treatments that are more effective than either of the two alone. Yet while the potential benefits of combination therapy are substantial, so are the developmental, technical, regulatory, and business barriers to such collaborative approaches.
Excitement about the potential for neuromodulation technologies is tempered by concerns the development may be getting ahead of regulation and scientific insight, said Alvaro Pascual-Leone, professor of neurology and associate dean for clinical and translational research at Harvard Medical School. Several workshop participants noted that little is known about the mechanisms of action affecting clinical improvement, and therefore, more evidence is needed. Hank Greely, director of the Stanford Program in Neuroscience and Society at Stanford University, agreed, noting that the use of neuromodulation devices has been creeping up without as much attention as in other areas of medical product development. He and several other workshop participants also discussed the ethical considerations around the use of non-invasive neuromodulation, such as off-label OTC use.
BOX 1-1
Statement of Task
An ad hoc planning committee will plan and conduct a 2-day public workshop to explore opportunities, challenges, and ethical questions surrounding therapeutic and non-therapeutic uses of non-invasive neuromodulation of the central nervous system (CNS).
Presentations and discussions will be designed to:
- Highlight potential benefits and risks of non-invasive neuromodulation based on known short- and long-term CNS mechanisms of action.
- Explore the scientific landscape of non-invasive neuromodulation device development for both therapeutic and non-therapeutic uses.
- Consider issues concerning vulnerable populations such as children.
- Explore the scientific landscape of non-invasive neuromodulation device development for both therapeutic and non-therapeutic uses.
- Consider the regulatory landscape for non-invasive neuromodulation devices.
- Discuss potential outcome measures for therapeutic uses in regulatory processes.
- Explore pathways for regulatory approval of therapies utilizing a combination of non-invasive neuromodulation devices and pharmaceuticals.
- Discuss differences in regulatory pathways among countries.
- Explore current and potential use reimbursement practices for therapeutic use of non-invasive neuromodulation devices.
- Explore the evidence base and acceptable therapeutic outcome measures utilized in reimbursement decisions.
- Consider economic outcome measures used to determine payer practices.
- Explore the evidence base and acceptable therapeutic outcome measures utilized in reimbursement decisions.
- Examine ethical questions around the use of non-invasive neuromodulation devices.
- Consider ethical issues of off-label and over-the-counter use on regulation, reimbursement, and patient safety.
- Discuss the use of these devices for enhancement in individuals without an impaired baseline.
- Consider the implications of involuntary or coercive use (e.g., children, court-ordered treatment).
- Consider ethical issues of off-label and over-the-counter use on regulation, reimbursement, and patient safety.
The committee will develop the agenda for the workshop, select and invite speakers and discussants, and moderate the discussions. An individually authored full-length workshop summary will be prepared by a designated rapporteur based on presentations and discussions held during the workshop in accordance with institutional guidelines.
The following report summarizes the workshop presentations and discussions. Chapter 2 provides an overview of the gaps, challenges, and potential opportunities for future research and policy action identified by individual participants. Subsequent chapters elaborate on these topics. Chapter 3 provides an overview of what is known about the neurobiological basis of non-invasive neuromodulation and the technologies that have been developed to deliver neurostimulation to the brain. Chapters 4 and 5 discuss therapeutic and non-therapeutic uses of neuromodulation, including its use as a tool for diagnosis, presurgical mapping, and research. Chapter 6 explores the use of neuromodulation to enhance brain function and performance, followed by a discussion of the ethical issues related to the use of neuromodulatory technologies in Chapter 7. Chapter 8 provides a brief overview of the regulatory pathways for both therapeutic and non-therapeutic devices in the United States and Europe. Included in this chapter is a discussion of the challenges of conducting clinical trials of neuromodulatory devices. In Chapter 9, challenges of reimbursement are discussed. Chapter 10 provides an industry and venture capital perspective on the challenges for businesses that are developing non-invasive neuromodulatory devices.
