FDA Defends Decision to Approve Digital Aripiprazole

Members of the U.S. Food and Drug Administration’s Psychiatry Products division go on the defensive in a new article, responding to concerns about the agency’s approval of digital aripiprazole.

Rebecca Troeger
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In a perspective piece published recently in the Journal of Clinical Psychiatry, members of the Psychiatry Products division at the U.S. FDA’s Center for Drug Evaluation and Research respond to critiques of its approval of digital aripiprazole late last year. The authors — one of whom is the division’s director, Mitchell V. Mathis — state that discussion surrounding the drug’s approval has been “obscured by sensationalism.”

“We hope that this piece facilitates a more rational and measured dialogue surrounding the product’s actual capabilities, FDA’s decision to approve the product, and any ethical concerns raised by the product,” the authors write.

Photo Credit: Raw Pixel

In November 2017, the U.S. FDA approved digital aripiprazole (brand name Abilify MyCite). The drug’s maker, Otsuka Pharmaceutical, and its digital technology collaborator, Proteus Digital Health, first filed a new drug application (NDA) for digital aripiprazole with the FDA in September 2015. This NDA was rejected in April 2016, at which time the FDA requested further information, including data on the drug’s functioning under real-life conditions, and additional human factors studies. Proteus/Otsuka resubmitted their NDA to the FDA, along with the requested information, on May  7.

Digital aripiprazole’s clearance is notable in that it represents the first approval of a drug with a “digital ingestion tracking system” in the U.S. Equally remarkable is the fact that such technology was first approved for use in an antipsychotic drug. As Dr. Paul Applebaum, Director of Law, Ethics and Psychiatry at Columbia University told the New York Times, “You would think that, whether in psychiatry or general medicine, drugs for almost any other condition would be a better place to start [with digital technology] than a drug for schizophrenia.” It is also worth noting that Otsuka’s U.S. patent for aripiprazole expired in April 2015, not long before the company submitted its first NDA for the digital version of the drug.

Public reactions following the drug’s approval ranged from highly critical to admiring. The article’s authors hone in on the critical responses, however — including a perspective piece in the New England Journal of Medicine (NEJM) titled “Swallowing a Spy” — which they characterize as sensational.

“Recent publications expressed a wide range of concerns regarding the product, such as its potential to infringe on patient privacy and autonomy, create an adversarial dynamic between clinician and patient, be used in medicolegal situations, or affect insurance coverage,” the authors write.

The authors make a case for the FDA’s approval of digital aripiprazole by emphasizing the fact that their review of the drug and its related components (its internal sensor, the skin patch with which the sensor communicates, a mobile app, and web portal) was based on the results of human factors studies that examined whether patients “could use the product as intended,” as well as a safety assessment of adding a digital sensor to the drug. They state that the FDA focused on the extent to which the digital version might “interfere with prescribed… use,” as well as on identifying and reducing error in order to enhance “simplicity” of use.

Interestingly, one of the authors’ arguments in support of the drug’s approval is that “no data were collected during the product’s development suggesting that the product impacts adherence or influences patient behavior.” It is curious that a drug depicted as a boon to patient adherence was approved without review of its effects on adherence (or patient outcomes).

The authors also maintain that the FDA and Otsuka share the public’s concerns about “the potential ethical issues of monitoring drug ingestion,” and that in fact, the FDA worked closely with Otsuka to deal with some of these issues. They state, for example, that the requirement that patients “actively choose whether to share their information with clinicians and caregivers” was added based on recommendations from a team of bioethicists with whom Otsuka consulted regarding patient privacy issues.

Lastly, the authors assert that some of the public’s fears are based on “inaccurate assumptions” about the drug — for example, they state that the drug sensor’s Bluetooth signal is encrypted and cannot be intercepted, and that the patch does not contain a GPS transmitter and thus cannot act as a “spy,” as the NEJM piece’s title implies.

As they end the article, the authors write:

“The FDA shares the concerns raised by the public regarding potential product use in medicolegal situations and potential use by insurance companies in decisions to pay for care. Although it is outside the FDA’s regulatory and enforcement mandate, a national discussion could help determine if more efforts are needed to protect patient data from digital medicines and applications.”

In their closing sentence following this call for discussion, the authors take aim at their critics one last time, writing, “Our hope is that the necessary discussion rests on rational facts rather than emotional reactions to this new technology.”

 

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Lee, D. J., Farchione, T. R., Mathis, M. V., Muniz, J., & Muoio, B. M. (2018). US Food and Drug Administration’s Approval of Aripiprazole Tablets With Sensor: Our Perspective. The Journal of clinical psychiatry, (3). (Link)

18 COMMENTS

  1. This is spooky. The drug company is explaining that this thing can’t be used as a GPS tracking device, but nonetheless show me where this technology is not going to be directed at insuring drug adherence/compliance (i.e. they don’t care where you go, so long as you are taking your drug when you go there.) I certainly couldn’t imagine mental health courts not getting wind of this thing, and utilizing it in enforcing court orders.

  2. I still think that just dropping one of these creepy Abilify chip pills into a cup filled with warm grapefruit juice or vinegar would simulate the stomach acid needed for the sender chip to tell the pharma gestapo the pill was ingested.

    “The sensor, containing copper, magnesium and silicon (safe ingredients found in foods), generates an electrical signal when splashed by stomach fluid, like a potato battery, said Andrew Thompson, Proteus’s president and chief executive.” Read more https://www.madinamerica.com/forums/topic/defeating-the-abilify-chip-pill-by-fooling-it-into-thinking-its-in-a-stomach/

    • Yes, that’ll work if you carry the vial of fake stomach acid with you as your fake stomach.

      Another desperation tactic might be to ingest activated charcoal at the same time that you ingest the Abilify. Warning, though, activated charcoal will wipe out your nutrition. Don’t eat then, eat some other time. And also, charcoal will block up your plumbing so if that happens you need to keep on top of that.

      “Doctor, my patch must have fallen off in the shower. Suddenly I just don’t see it there, if that’s what you’re wondering. By the way, my aunt died and I will not be able to come to our next appointment. I will call once I am back in town. Maybe then I can get this patch replaced.”

  3. “You would think that, whether in psychiatry or general medicine, drugs for almost any other condition would be a better place to start [with digital technology] than a drug for schizophrenia.”

    You would only think that if you still see psychiatry as something as other than a tool of social control. “Schizophrenia” is still the all-encompassing ogre of choice serving to keep people terrified of crazy people, so a new way to control “these people” is a good tactical, and marketing, decision.

    Since they want to tamp down “sensationalism,” social media types should immediately get to work getting these “digital” drugs to be popularly nicknamed “spy drugs,” “1984 drugs,” or maybe something even catchier.

    What is the effect of hundreds of microchips collecting in ones bowels, I wonder. It should be also examined whether the components are known carcinogens.

    the requirement that patients “actively choose whether to share their information with clinicians and caregivers” was added based on recommendations from a team of bioethicists

    So that should mean no AOT people? (At least not until they make a “wise” decision, huh?)

  4. It certainly CAN act as a spy! That is its intent, to track on “compliance” so that doctors and their enforcement minions can locate “uncooperative” clients, especially those who are on conditional release agreements/AOT orders. There is no other real purpose for this system – it was designed for forced “treatment.”

    • Good point Steve, and true for the ‘clinician’ obsessed with power. But also follow the money. The producer can charge 1,000 times the cost of manufacturing generic pills with its new patent. Already Olanzapine has been repatented as a dispersible tablet, also for reasons of ‘compliance’ – and it is handed over to all and sundry regardless of the presence of ‘compliance’ issues or not. And Ely Lily have already scored 250 billion in profit on that one. I think Abilify was the most profitable drug in the early years of this decade. Have these people no restraints on their greed at all?

  5. “An investigative report uncovers little recognized and unpoliced potential conflicts of interest among those who serve on FDA advisory panels that review drugs. Some members of such panels are later receiving significant payments from either the makers of drugs they previously reviewed, or from competitors. … those asked to weigh in stand to gain tremendously in their further professional careers. “It’s in their best interest to play nice with the companies.” FDA may also have missed or judged insignificant financial ties physicians had before their service on the drug approval advisory panels.” http://science.sciencemag.org/content/361/6397/16