Where does patient adherence technology go in a post smart-pill era?

Opinion

November 15, 2017

Where does patient adherence technology go in a post smart-pill era?

Yesterday’s press release about Proteus’ $450 Million digital smart pill approval made the major papers.

WSJ (https://www.wsj.com/articles/fda-approves-worlds-first-digital-drug-1510621146) and NYT (https://www.nytimes.com/2017/11/13/health/digital-pill-fda.html) both offered in depth analysis of technology and user experience challenges. CNN (https://www.cnn.com/2017/11/14/health/fda-digital-pill-abilify/index.html), later in the day, noted that neither Proteus nor Otsuka were willing to comment. Oracle, who hosts the data platform, wasn’t even mentioned.

Interestingly, both original Big Pharma investors and sponsors of this technology are holding back, with neither Novartis nor Otsuka in a hurry to launch any drugs (not even the newly approved Smart Pill version of Abilify - https://www.abilify.com). The patient target group chosen to put through the FDA approval process (Schizophrenia) always seemed like an unfortunate choice.

The negative criticism was entirely predictable and isn’t surprising, because of a variety of factors:

1. User concern with data security. I don’t know a single person who is keen on swallowing a computer chip and wear a monitoring receiver on their body 24/7. Electronic ankle bracelet anyone? Proteus’ response to this makes no sense “the device stays inside the body and the data is stored in the patch”. Yes, my credit card stays in my wallet, too. But it’s of no use until I take it out to pay for something. The smart pill data has to go somewhere, and if it just stays inside the patient’s body, then there is no point having it at all.
2. Proteus states that the chip contains no more Silicon (Si) than a banana. That’s fine, perhaps, but who eats up to 3 or 4 bananas a day? Si is not completely inert, and even if it’s a trace mineral used by the body, too much of a good thing can be bad. The banana analogy is alarming, at best. According to WebMd (https://www.webmd.com/vitamins- supplements/ingredientmono-1096- silicon.aspx?activeingredientid=1096&activeingredientname=silicon) it could contribute to kidney stones, and its safety as a medicinal compound is unknown. It advises pregnant and breast feeding women to avoid intake of supplemental Si.
3. Usability. Proteus attempts to address non adherent (forgetful) patients. But it uses a very big hammer to hit a small mosquito by requiring a) a patient to wear a patch in the correct location, b) to make sure the patch is connected to their smartphone via Bluetooth, c) to make sure the smartphone is within reach and also connected to internet via WIFI or 3G/LTE link, d) to swallow the smart pill and not be concerned if there is no confirmation of the pill having been ingested for up to two hours, or indeed perhaps not being detected at all. So we are targeting poorly adherent patients with an overwhelming technology burden. That’s the opposite of smart. The biggest technology hurdle here is the battery running out of juice. And it warns that the ingestion event might not even be detected by that patch at all.
4. Tolerance of the patch. The patch is just like any other medical patch (pain or birth control patches, for instance). A good proportion of the population experiences contact dermatitis (https://www.medscape.com/viewarticle/572962). Proteus’ instructions are to change location of the patch each week when starting a new one. How many weeks would a patient put up with this? That’s a question that likely has been answered anyway: not too long. One of the main issues of adherence drop off is persistence, meaning patients stop being adherent after some time. The patch seems to just aggravate this issue, not solve it.
5. It doesn’t do what it is designed to do. Proteus’ smart pill does NOT address the intended purpose of the technology which is to improve adherence. Indeed, the FDA has directed Proteus to specifically say so on their device label. The fact is, adherence measurement does not equal adherence improvement; unless the measurement data are used in a specific way to coach patients about their adherence pattern.
6. Cost. Nobody has addressed cost, but there is a requirement to re-apply for a drug application each time a Proteus smart chip is combined with an existing drug. This costs time and money. In clinical trials, where adherence is of paramount significance, the combination of chip and pill might cause unacceptable delays and possibly then force the drug company to go to market with a chip inside every pill whether they want to or not. This would explain why no actual clinical trial seems to have included this chip in its research protocol. Clinical research involves careful study of side effects. Adding guaranteed side effects by using medical adhesive for the detection patch does not help matters.

There have been effective adherence measurement devices in the market for 30 years. MEMS by Aardex is a smart cap for medicine bottles and has been used in hundreds of studies. eCAP by Information Mediary Corp. is a similar, more modern version of this, and has been in use for over 10 years. Med-ic, also by Information Mediary Corp., is a smart chip inserted in medication packaging to record and transmit medication event histories. In all cases where the chip is part of the packaging, rather than inserted into the actual medication, FDA does not require complicated, lengthy and expensive approvals. The technology has been used by hundreds of thousands of patients over more than two decades. It is robust, affordable and easy to deploy.

What makes package-based adherence monitoring the sensible choice for researchers and clinicians alike is the fact that it can be innocuous to the patient.

The patient has to do absolutely nothing, except to take their medicine as usual. The argument of the smart-pill advocates that removal of medication does not prove ingestion is correct. However, it has been shown to be highly correlated.

What is required to drive adherence measurement technologies forward is user adoption. Some pharma and clinical trials teams have waited for the magic smart pill in favor of adopting simpler smart packaging devices. Now that day of reckoning has arrived with Proteus’ FDA approval. The magic has been exposed as just an expensive technology play.

Again, the basic premise that adherence measurement does not in and by itself lead to adherence improvements means that pharmaceutical brand and research teams need to get back to basics. Yes, collect adherence data, but then use it diligently to shape and apply adherence coaching and patient management strategies.

Perhaps to Novartis and Otsuka, their investments in Proteus amount to rounding errors, but instead of a smart pill, they swallowed a bitter one. Oracle has been keeping a very low profile, despite being an early investor. Yesterday was their Juicero (https://www.theguardian.com/technology/2017/sep/01/juicero-silicon- valley-shutting-down) moment perhaps.

One positive outcome is for certain - the Proteus experiment has brought the importance of patient adherence to the forefront of discussion once again. Luckily, sensible technologies already exist to collect adherence data, in the form of smart packaging from leading vendors such as Aardex (Westrock) and Information Mediary Corp.

Michael Petersen is co-founder and C.O.O. of Information Mediary Corporation, which has been developing and deploying smart packaging technology since 2001. Over 1.5 Million devices have been sold to-date including over 1 Million smart blister packages used in pharmaceutical clinical trials. Michael is an advocate of sensible technology deployment, and has been a vocal critic of previous technology hypes in the RFID and smart packaging space. He can be contacted at [email protected]