The Case for Functional Indications in iBCI Development: Don't Leave Rare Disease Patients Behind

As invasive brain-computer interface (iBCI) companies race toward FDA approval, they face a critical strategic decision that will determine whether their technology helps all the people who could benefit —or just a select few. The choice? Pursuing narrow, disease-specific indications versus broad, functional indications for use.

From a financial point of view, if companies can win reimbursement of $150K to $250K then every single implant matters for the bottom line to sustain the company and make life-changing technology available for the next person.

The Current Trajectory: A Recipe for Exclusion

Most iBCI companies are targeting their pivotal trials at specific etiologies: ALS, high cervical spinal cord injury, and brainstem stroke. While understandable from a trial design perspective, this approach creates an immediate problem the moment FDA approval and CMS coverage are secured. A young man with Duchenne muscular dystrophy (DMD) who is quadriplegic, cognitively intact, and desperate for communication and control? Denied. A person with advanced spinocerebellar ataxia who has lost all functional arm movement? Not covered. Someone with severe Charcot-Marie-Tooth disease who meets every functional criterion? Out of luck.

The irony is cruel: these patients often represent ideal candidates—younger, highly motivated, with stable conditions and long life expectancies that would maximize the benefit of an iBCI system. Yet they'll be excluded not because the technology won't work for them, but because the FDA indication was written too narrowly.

The Solution: Follow the Functional Indication Playbook

There's already a roadmap for how to do this right. Consider:

• NuedEXta: Approved for "pseudobulbar affect"—the symptom itself, not ALS or MS or stroke specifically

• MyoPro: Approved for "arm weakness," regardless of whether it stems from stroke, brachial plexus injury, or spinal cord damage

• InterStim: Approved for "urinary urgency/frequency" and "fecal incontinence" as functional problems across etiologies

• FES foot drop devices: Approved for the functional impairment, not the disease causing it

  
  

These precedents demonstrate that the FDA can and does approve devices and drugs based on functional deficits rather than disease-specific etiologies—especially when the mechanism of action targets a final common pathway.

What a Functional iBCI Indication Should Look Like

iBCI companies should pursue an indication for use that specifies functional criteria:

"For adults with quadriplegia from any etiology who have:"

• Bilateral upper extremity dysfunction (e.g., Action Research Arm Test score <10 in both hands)

• Sufficient cortical integrity to generate decodable signals, as demonstrated by:

  • Scalp potentials in response to single-pulse TMS or focused ultrasound (corticocorticopotentials)

  • EEG patterns with adequate Perturbational Complexity Index values indicating preserved cortical network function

Note: I have chosen objective metrics, including physiological measures that don't require a ventilator-dependent person to undergo an exhaustive MRI which may be technically complex and medically risky.

This approach ensures that anyone meeting the functional criteria—regardless of whether their quadriplegia comes from ALS, SCI, DMD, spinocerebellar ataxia, CMT, or any other condition—can access the technology.

Addressing the Surgical Risk Red Herring

Some might argue that different etiologies carry different surgical risks. For instance, patients with DMD may have cardiomyopathy that complicates anesthesia. But this is a general surgical risk, not a device-specific risk. The FDA's role is to assess whether the device itself is safe and effective for the intended functional use—not to practice medicine by determining which patients can safely undergo surgery.

Patients and their physicians must retain the autonomy to assess individual risk-benefit profiles. A skilled anesthesiologist can mitigate cardiac risks in DMD patients. A neurosurgeon can adjust techniques for patients with altered anatomy. These are standard elements of surgical planning, not reasons to exclude entire patient populations from device approval.

The FDA has consistently recognized this principle: surgical risks that vary by patient comorbidity or underlying condition should not dictate device indication boundaries when the device mechanism itself addresses a common functional deficit.

The Stakes Are High

Once an iBCI receives narrow disease-specific approval, expanding that indication is difficult, time-consuming, and expensive. Meanwhile, patients with rare conditions—who may be perfect candidates—will wait years or decades for access, if they ever get it at all.

The time to get this right is now, during pivotal trial design and FDA discussions. iBCI companies have the opportunity to be pioneers not just in neurotechnology, but in ensuring equitable access to transformative therapy.

The technology doesn't discriminate by diagnosis. Neither should the indication for use.

The path forward is clear: Define success by function, not by disease label. The patients who will benefit most from your technology are counting on you to get this right.

ADDENDUM: The Regulatory Reality and Path Forward

The Uncomfortable Truth

Regulators love precedent for first approvals, and would be expected to resist contradictory precedent for subsequent ones. The issue isn't that iBCI companies are ignoring rare disease patients—it's the concern that the FDA's habit is to actively steering them toward disease-specific indications despite functional precedents existing elsewhere in the agency.

FDA expects iBCI companies to demonstrate benefit>risk for each patient group defined by etiology within study samples. Endpoint development centering on participant function has been met with queries about validation per patient group by etiology. Companies face the specter of narrow approvals if pivotal trial enrollment is unevenly distributed across etiologies—which is inevitable without rigid enrollment quotas.

The trade-off being presented: accept disease-specific indications for a faster, lower-resistance initial approval, with the understanding that etiology-agnostic expansion will be "arduous" later. Should sponsors be pushed into this choice?

Learning from Precedent: What the Labeling Actually Says

The details matter. Consider these examples:

DEKA Arm (510(k) Summary): The Indications for Use raise immediate questions:

• Why limit to "18 years or older" rather than "skeletally mature"?

• Why specify "amputation" versus "congenital limb deficiency" rather than simply "absent limb"?

• The phrase "to assist in activities of daily living" is likely why CMS coverage depends entirely on geographic lottery—where you live determines whether your local Medicare Administrative Contractor considers it "medically reasonable and necessary," based on local politics and cost tolerance rather than science.

Indego Exoskeleton (Product Code PHL): The IFU states it "is intended to enable individuals with spinal cord injury at levels T3 to L5 to perform ambulatory functions." Notably, "spinal cord injury" encompasses both traumatic and non-traumatic etiologies—in principle covering SCI from stroke, tumor resection, surgical injury, or severe transverse myelitis. This language offers useful flexibility.

The key insight: It may not be the Indications for Use section that needs broadening, but rather careful formulation of the Warnings/Precautions sections to avoid creating payer ammunition for denials.

The FDA-CMS Labeling Paradox

FDA and CMS use device labeling in fundamentally different ways:

• FDA wants to ensure safety and effectiveness for the appropriate population

• CMS wants to contain costs and searches labeling for any justification to deny coverage

Even though FDA emphasizes it does not practice medicine, and CMS officially claims cost is not considered (despite protestations to the contrary), payers ruthlessly mine warnings and precautions to argue devices are "not medically necessary" for specific patients or that patients fall into "high-risk" categories the manufacturer supposedly doesn't endorse.

The solution: Align clear biomarkers of response with IFU language and precautions. This satisfies everyone—companies get paid when patients are appropriate candidates; payers avoid paying for inappropriate candidates. The better the objective criteria, the less room for arbitrary denial.

What Companies Can Do Now

Every iBCI company can leverage the Pre-Submission (Pre-Sub) process strategically:

1. Specifically request feedback on functional indication language, citing multiple supporting precedents (NuedEXta, MyoPro, InterStim, Indego)

2. Request formal meetings with senior review staff (not just project managers) to discuss regulatory rationale

3. Ask FDA to document concerns about functional indications in writing—creating a record that can be referenced and challenged

This strategy benefits all stakeholders: investors, patients, physicians, and FDA itself.

What Won't Work

Blog posts won't change this. Informal discussions—even with every KOL on Earth—at iBCI-CC or conferences won't alter the trajectory. The community must compel FDA, CMS, and legislators to respond in writing. Not in an adversarial way, and instead with a genuine open-hearted partnership to make sure all the children and adults who could benefit from these life-changing technologies can do so.

Possible formal mechanisms:

• Citizen Petitions requesting FDA develop guidance on functional indications for neurorehabilitation devices (though these rarely drive change alone)

• Public Workshops specifically on functional vs. disease-specific indications (though FDA may defer to iBCI-CC)

• Medical Device Development Tools (MDDT) program (though this takes years and doesn't guarantee uptake by review divisions)

The reality: FDA has largely handed off policy development to the iBCI-CC. If this community sees the current direction creating more uncertainty than it resolves, the iBCI-CC must take ownership rather than rely on FDA or CMS to lead.

The Core Principle Bears Repeating

Some might argue that different etiologies carry different surgical risks. For instance, patients with DMD may have cardiomyopathy that complicates anesthesia. But this is a general surgical risk, not a device-specific risk. The FDA's role is to assess whether the device itself is safe and effective for the intended functional use—not to practice medicine by determining which patients can safely undergo surgery.

In meetings over years, FDA has proven quite sensitive to the point that they do not practice medicine. The challenge is leveraging this awareness into indication approvals that empower physicians to use their expertise and skill—not labeling that gives payers weapons to override clinical judgment.

The Stakes Remain

The first iBCI approval will set precedent that shapes the field for decades. We have one chance to get the regulatory framework right. Disease-specific indications will create access barriers the moment they're granted. Functional indications require more careful negotiation now but prevent orphaning rare disease patients forever.

The question is whether the iBCI community will accept the path of least regulatory resistance today, or fight for the framework that serves all patients who could benefit tomorrow.

The people with the conditions, their families, their physicians- must take the lead in steering the conversation, and my understanding is that both the FDA and CMS were created by the laws we as a nation invented to serve the people, and that the details on how those agencies were built may render them fundamentally reactive rather than proactive and visionary, even if people with proactive vision do work there.

Will the community coalesce around "this is the functional indication-for-use we want and need" and get FDA and CMS to commit to it? Can we shift the conversation away from a focus on disabilities and towards the capabilities people need to become independent?