Proteus Digital Health published a paper on its ingestible sensor that explains the design of the sensor, the safety tests Proteus completed, and the clinical trials Proteus conducted with 412 patients who used the system over 5,656 days.
The Proteus digital medicine platform is a medication management and adherence system that includes unique measurement tools, like sensor-enabled pills, a peel-and-stick biometric sensor patch worn on the body, and companion smartphone apps. The patch records when a pill is ingested and also tracks other things like sleep patterns and physical activity levels. The ingestible sensor component secured FDA clearance in July 2012, while the company’s sensor-laden patch got FDA clearance in 2010.
The ingestible sensor is made up of an integrated circuit, two "active" layers, "excipient materials" that provide adhesive, and a "skirt, which contains ethyl cellulose, hydroxypropyl cellulose, and triethyl citrate. The company explains in the paper that the pill is made entirely of ingredients found in food.
Before human trials, the sensor underwent several safety tests. Proteus performed chemical extraction studies in which researchers studied the effects of the sensors when placed in deionized water; toxicology studies that were performed on animals to test their reactions to the pill; mechanical safety tests to measure gastric transit time; and electrical safety tests to measure cardiac stimulation.
The company then used the sensor in a series of clinical trials. Patients in the trials had various health conditions including hypertension, heart failure, diabetes mellitus, tuberculosis, bipolar affective disorder, and schizophrenia. While the studies were analyzed separately, the company also aimed to look at the aggregate performance of the sensors.
To do this, the company measured the performance detection accuracy (PDA) of the sensor, which identifies how many sensors administered under direct observation were detected. The 412 patients ingested a total of 20,993 sensors. They ingested at most 34 pills per day and used the pills 90 days at most. The company found that the "PDA" was 99.1 percent.
Proteus explains in the paper that the sensor was designed for two purposes.
The first is that the patient can use the sensor to measure their medication adherence. The sensor is taken at the same time as the user's medications so that it can mark the time that the medication was taken and how adherent a patient was after this time.
Users can also take the pill with nutritional supplements and different foods so that they can understand how these foods and supplements affect their athletic performance, and how adjusting their diet could make their performance better.
Proteus suggests three different ways to take the ingestible sensor with other medications. It can be added to a drug when the drug is still in powder form, added to the pill in a gelatin capsule during the drug's "capsule filing", or attached to a drug with an adhesive layer.
"It is important to note that the detection accuracy of such events need not be perfect, rather only sufficient to provide a statistically meaningful classification of adherence behavior within a reasonable period of time," the company writes. "The higher the detection accuracy, the fewer ingestion events needed for such classification for a given statistical level of confidence."
Last week, Proteus announced that it raised an additional $52 million from undisclosed investors following a $120 million raise the company announced in June. That brings Proteus’ latest round of funding — its seventh — to $172 million. By our count the company’s total known funding is now close to $400 million, which makes it one of the most-funded, private companies in digital health.