Post by Roland Nadler
Next time you impulsively pull up YouTube to check out the adorable cat video du jour, you might find your fix delayed by a most unusual advertisement:
Or by this one, with all the subtlety of a ten-ton hammer:
Or by this one, approximating the style of your typical YouTube vlogger:
Though they run the gamut of production values, these ads all lead to information about how the device being marketed is “FDA-cleared” to treat a variety of psychological ills such as anxiety and insomnia.
What’s going on here? What are these stimulators, and what does it mean to say that they have clearance from the Food and Drug Administration?
Let’s start with the basics. The devices in these ads are known to regulators as Cranial Electrotherapy Stimulators. They work by running a fairly weak electrical current through the head – these ones in particular use alternating current, sent through the user’s scalp by way of wet-sponge electrodes. What happens within the cranium when this technology is turned on is … anyone’s guess, really. It seems that the electricity causes affected neurons to be more excitable, but it is not known why making certain brain cells eager to fire would, say, cure insomnia.
Fortunately or unfortunately depending on your view of things, we needn’t have any understanding of how or why a therapy functions in order for regulatory authorities to approve it for consumers. In the US, drugs and devices must be safe, and for the most part we require that they be effective. So it goes with these CES products, which are classified as medical devices. In fact, they have been on the market for over 30 years, though the technology has remained relatively obscure until recently.
FDA regulates medical devices somewhat differently from drugs. Ordinarily, drugs require extensive scientific studies (multiple clinical trials, familiar to many as Phase I, Phase II, and so on) before they can go on the market. But – to give a quite drastically simplified overview of it – devices are different. About 57% of medical devices don’t require any pre-approval at all: these are devices in FDA’s “Class I” (e.g., band-aids) or “Class II” (e.g., motorized wheelchairs) categories. There is also a “Class III” category, which includes items like defibrillators and knee replacements. A Class III device must go through pre-market approval – usually via a clinical trial for safety and efficacy.
To every rule there is an exception, and for the pre-market approval requirement, there are two exceptions. One is a grandfather clause involving devices marketed before 1976, and the other is a regulatory allowance (or loophole, depending on how you feel about it) known as 510(k). Basically, 510(k) approval allows a device to bypass the usual Class III approval requirements if the manufacturer can convince FDA that the device is “substantially similar” to a “grandfathered” Class III device, or one that has already been cleared. The regulatory history when it comes to CES devices is long and confusing, but suffice it to say that thanks to one or both of those exceptions, CES devices seem never to have undergone the full pre-market approval via clinical trial.
Fast forward to 2012. Fisher-Wallace (the company behind the stimulator in those ads), along with Electromedical Products International and Neuro-Fitness (two other companies in the CES space), was alarmed at a 2011 proposed rule by FDA to revoke the 510(k) option for CES devices. The companies petitioned FDA to make the opposite move – to place CES in a more lenient regulatory category altogether, relegating it to Class II rather than the status quo of Class III plus 510(k). And in February of 2012, FDA’s Neurological Devices Panel met to come to a decision.
By all accounts [NB: source behind paywall], this meeting was controversial. In fact, Fisher-Wallace was so displeased with the procedure and the outcome that they have filed a citizen’s petition on the matter and have even contemplated a lawsuit against the agency. At any rate, in the meeting, it was mostly agreed that the safety data for CES were fairly strong. But FDA remained skeptical of the efficacy data. Perhaps the biggest disagreement arose over just what would be best for the public given the uncertainty of the data. The industry argued that patients with issues like insomnia, anxiety, and depression deserve access to low-risk treatments even with shaky efficacy data, because so many of them are dissatisfied with their other treatment options. Which, I think, is a reasonable argument; drugs are often Not Very Pleasant, and patients with treatment-refractory conditions are quite understandably looking to take the kitchen-sink approach.
Meanwhile, FDA worried that giving patients access to a potentially ineffective device could lead to a great deal of harm by allowing psychological conditions to worsen due to the patient’s choice not to use a more effective treatment. This, too, strikes me as a valid concern. Suppose, for instance, that CES were being marketed for treatment of bipolar disorder. (It is not … yet. I think it will be soon. Moreover, it has been studied, and I rather wonder why it has not been marketed for bipolar depression already). Patients who do not get their bipolar disorder under control with an effective intervention after the first break tend to experience mania-depression swings of increasing severity. With such a narrow window before the disorder becomes unmanageable, proven efficacy is indispensable. A patient understandably seeking to avoid the grueling experience of treatment with lithium might miss that window by relying on CES instead.
Ultimately, the industry’s view failed to convince the Neurological Devices Panel, which recommended to FDA that it finalize the following rule: CES devices are Class III and cannot, going forward, evade pre-market approval via 510(k).
So then, what is Fisher-Wallace talking about when it advertises its stimulator as enjoying FDA clearance? It is a bit of a mystery to me. They just suffered a considerable – and from the look of it, rather upsetting to them – regulatory setback. Now, that is not to accuse Fisher-Wallace of any dishonesty about their regulatory situation. The Panel only recommended a rule to FDA; until the rule is finalized by the agency and a specific “effective date” is established for the pre-market approval requirement, the status quo endures. Still, it would be more candid – if not exactly good for business – for these ads to depict a little Sword of Damocles suspended over the words “FDA-cleared.”
Now that we have made sense of the legal details here (at least, as much sense as can be made), I would just step back and make one more point regarding the bigger picture.
I will be the first person to agree that it would be wonderful to have another safe, effective, inexpensive alternative to drugs for the treatment of mental conditions. The world would be a better place if we made that happen swiftly. And these sorts of “electroceuticals” could even prove useful in enhancing cognition, which is for many an exciting prospect (if, admittedly, a topic fraught with ethical issues of its own). All of this is well and good … but. I do think a great deal of regulatory caution is warranted here, and the most important reason in my view is one that seemed to enjoy very little prominence in the industry-agency discourse that took place.
To wit: these are devices made for home use by end-users. They are portable and self-applied. And as of now there is very little information available at any level – FDA or the products themselves – regarding the proper placement of the electrodes, or regarding what happens if they are not placed correctly.
In other words, the safety results we have now are based on proper use, but that tells us next to nothing about how safe it is in real-world terms to hand consumers CES stimulators and send them on their way, free to bemusedly zap their brains without detailed guidance about how to zap safely. People could hurt themselves, needlessly so.
Consider a related (but, for FDA purposes, different and apparently as-yet unregulated) technique called transcranial direct current stimulation (tDCS). One study evaluating whether tDCS could enhance people’s arithmetic skills noted that, when experimenters switched the anode and the cathode (essentially throwing the electrical current through the brain into reverse), the participants’ mathematical abilities were reduced. That’s a scary result.
CES is usually alternating current, so that particular risk is less of an issue, but it nonetheless serves as a case in point: shooting electricity through one’s brain is probably not an amateur-hour undertaking. Sure, there are lots of things that people could hurt themselves with that we regulate minimally or not at all. But electroceuticals are probably much more like prescription drugs, in that they require expertise to use wisely. At the very least, we should assume that they are until we have a compelling case, supported by extensive evidence, to the contrary.
I haven’t personally held a CES device in my hands, but I have gotten to play with a tDCS device (no, I didn’t work up the gumption to actually turn it on). I can say from handling it that putting it on my head in reverse or arranging the electrodes crookedly, off-center, or otherwise wonky would be unsettlingly easy.
And the instructions on the device I looked at were disappointingly vague and imprecise about the placement issue, and about safe and proper usage generally. From looking at images of CES devices, the same appears to be true of those.
So, not only are there apparently newly-minted legal reasons for regulators to pipe up when these ads give the impression that FDA has signed off on the technology, but it seems to me there are nontrivial policy reasons for some caution as well.
On the other hand, maybe I can make use of one of these stimulators to break my near-compulsive habit of watching adorable cat videos on YouTube …
Roland Nadler is a 2L at Stanford Law School, the student fellow at the Center for Law and the Biosciences, and co-director of the Stanford Interdisciplinary Group on Neuroscience and Law (SIGNAL).