NeuroVoices: Michael Okun, MD, on Reforming the Device Approval Process

Michael Okun, MD

A recently published editorial in JAMA Neurology by Michael Okun, MD, and James Giordano, PhD, highlighted some of the major flaws with the process in which deep brain stimulation and neurotechnological devices are approved for patients with rare diseases. While the process for requesting orphan drug designation for the use of specific drugs may be more straightforward, neurotechnological devices that are developed and/or can be used for rare diseases do not benefit from the same approval process.

Humanitarian device exemptions (HDEs) have been used as a regulatory pathway for device availability in rare diseases but are slowly being phased out due to industry partner concerns over the costs required to develop and maintain the HDE, as well as limitations of profit, tax exclusivity, lack of incentives, and legal liability. Okun and Giordano touch upon multiple issues within the system, including the barriers set by insurance companies which force patients who seek this selective type of care to pay out-of-pocket costs.

Okun, the executive director of the Norman Fixel Institute for Neurological Diseases, and Adelaid Lackner Professor and chair of neurology at the University of Florida, also serves as the medical director of the Parkinson’s Foundation. He calls for major reform throughout the paper, with an emphasized use of disease-based registries and modifications to the preexisting condition clause of the Patient Protection and Affordable Care Acts.

As part of the NeuroVoices series, Okun sat down to provide in-depth explanation of the flaws of approval system for neurotechnological devices for patients with rare diseases, and why they do not receive the same standardized process that clinical drugs have as they go through the pipeline. He also touched on the issues that stem from insurance companies and why change is only attainable if all levels are engaged at the discussion table.

NeurologyLive: Why do neurotechnological devices that are developed for rare diseases not receive the same benefit as other drugs that may receive orphan drug status? Where is the disconnect?

Michael Okun, MD: I would back up first and say that we’re dealing with a system that’s decades old in place, even before the advent of all these new devices and precision medicine. I don’t know that when it was first constructed but people saw these devices, particularly brain and spinal cord, not the way they see them as such transformational therapeutics. You’re dealing with a system that was designed for drug development, which is sometimes way easier. You take a pill, you document what happens with the pill, and decide yes or no. Same way vaccines were developed as well. When you implant a device, there are bumps in the road. When you implant that device in a human, there’s no blood supply, so the device can get infected. Even if you take an antibiotic, you may not be able to clear that section, and the device may have to come out. This can be anything from a pacemaker for the brain, to a spinal cord stimulator. Anything that you can put in has the potential to get infected and come out. There are hardware issues, things can break, there can be fractures, and pieces that need to be replaced. Additionally, there can be updates, software issues, all of which are not seen by pharmaceuticals in general.

The pharmaceutical industry has a heavy lobby, with a lot more money in it. I don’t think we should kid ourselves with that. If you lift the hood of the car, you’ll see that this is a very strong lobby group. I’m not judging that; I’m just stating the facts. But the device industry is expanding. Now you have a situation that nobody really anticipated. Let’s be fair, I don’t think even the smartest among us anticipated a situation where we might have a precision medicine for devices.

What do I mean by precision medicine? You could have a rare or a common disease, like Parkinson disease (PD), with a rare symptom. In that case, you can actually target a specific circuit in the brain and treat that symptom. The brain has added a level of complexity to the conversation. If you’re talking about the gallbladder, not that there’s anything wrong with the gallbladder, but the distributed network of the nervous system is amenable to being targeted by neuromodulation techniques. We can change the way the different areas communicate with each other and thereby, change individual symptoms.

Now we can change the paradigm. Normally, we get a drug, have it approved, and watch it treat the disease to the best it can. Now we have a situation where a device can be applied to a circuit as well which is very different. We have to appreciate the upside of that. The problem is that if we continue to have a process that is streamlined in the same direction as every drug, that leaves rare diseases out of the picture, or lessens their chance of moving forward. We mentioned in the report that if you’re involved in the drug development of rare diseases, you incentivize people to stay in the game. Those aspects don’t exist on the device side. In fact, what happens is that the cost to the manufacturer can be so high and the legal exposure can be at a level that creates an impossibility for a business to want to do business and get involved.

The example I’ve been involved with for many years stems from a grant from the Tourette Association of America. We have a publicly available database that has tracked 320 cases around the world for many years. Tourette still has no approval, but yet we know that our database works. We know that people with Tourette can have these head snapping tics where they can fracture their neck and become quadriplegic. They can have self-injurious behavior, which can lead to severe consequences to school, social isolation, and acceptance. We have a treatment that can suppress the motor and vocal aspects of Tourette by 40% to 50% better in most series with multiple targets, but we can’t apply it.

We’ve written about a bait and switch, which happens when both an insurance company agrees, their medical director agrees, and the conversation leads to confirmation about a patient having surgery. When payment time comes, they don’t pay for the device. They feel as though they aren’t obligated. We must recognize that we have shifted into a new era, and that we have to have a pathway for rare diseases and devices that can be used to treat these rare diseases or rare symptoms of common diseases.

The humanitarian device exemptions (HDEs) are beginning to fall apart as an option because insurance companies can still refuse payment on those. Device manufacturers are beginning to say, “Whoa, we don’t want this. We have legal risk. We have a million or so bucks to spend on someone patrolling this, along with all these complications and regulations. It’s not our core business anyway. Why do we want to bid?” Now I have to hold onto something that can help our kids and adults with Tourette, for example. Even if I can give it to them, the insurance company is going to bait and switch anyway. Our piece addresses the gaps. We have to have a process where we can move this in a different path. It’s reasonable to have data, but there should be a lower standard, especially if the data is done through foundations and universities and is publicly posted.

On the industry side, people should be given a legal break. Not a pass, but there should be breaks and incentives for them to make these devices available which can end up being life changing innovations for these various disorders. If we don’t do that, we’re going to be in trouble or just sitting on a lot of technology that can’t actually get out to these people with rare diseases.

How much blame is on insurance companies? Do you feel as though we are ever going to reach a point where they finally give that right-to-try?

There’s blame to go around all the way. If you give an insurance company an inch on a loophole, they’re going to take it. It’s a business, and we’ve given them a loophole out, so they’re going to exploit it. We haven’t held them accountable. My argument has been that they shouldn’t be able to loophole out of approvals from various things. They’ve loopholed out even when people have HDEs. They haven’t been paying for obsessive compulsive disorder cases, here, at the University of Florida, even with an HDE in place. In other places around the country, even though there’s an HDE, they don’t want to pay when there’s an ID or experimental IDE that’s in place.

They need to be pushed to say, “Yes, you do have that burden.” I would argue this is not necessarily a violation, but a direct conflict to the pre-existing conditions within the Affordable Care Act, because it appears to me that they’re not offering a treatment for a pre-existing condition. They would respond by saying we (clinicians) haven’t established the data and conversed with the regulatory agents, but that just leaves us stuck. You have to fix both parts of the system to get the wheel moving again. Let’s say you do allow people to post their data on public databases, and the FDA agrees there is enough evidence, then they should be held to a pre-existing standard. They shouldn’t be able to try to get out of that. This will probably reduce the long-term morbidity of the cases when its applied in the right situations as well as save these people money within their insurance systems.

There is a method to the madness, but there a few points in this wheel which make it complicated that need addressing. Industry needs to be given more of an incentive to stay in the game. Universities and foundations need to be allowed to track their own data. Remember, you’re going to need industry to submit on all the side effects and the upkeep of all of these things. The FDA is going to want to see that we’re not going to be able to provide on the device that’s being used. There has to be a way to track, and then there has to be a way within the law for us to say to insurance companies, “you can’t just say there’s a carve out or walk away from people with medical diseases.” I think there’s a few touchpoints that we get out with this piece that are very important.

Transcript was edited for clarity.