Digital Pill May Improve Adherence to Oral Cancer Drugs

Roxanne Nelson, RN, BSN

February 06, 2019

Oral chemotherapy has changed the paradigm of cancer treatment, moving it from the inpatient to the outpatient setting. Although more convenient for the patient, adherence can sometimes be problematic.

A new "digital pill" may allow clinicians to better monitor their patients.

In a small pilot study, colorectal cancer patients are being administered capecitabine (Xeloda, Hoffman-LaRoche) that has been embedded with a sensor. The sensor can alert the oncologist, nurse, or caregiver when the pill has been taken.

Developed by Proteus Digital Health, the product can securely capture, record, and share information about the time, dose, and type of oral chemotherapy medication taken. The goal is to help optimize treatment regimens while maintaining the patient's privacy, the company says.

The study, which is currently underway, includes seven patients with stage III or IV colorectal cancer. The technology is being developed in collaboration with the University of Minnesota Health and Fairview Health Services.

"We were interested in making oral chemotherapy safer and more practical," said Edward Greeno, MD, professor of medicine, Division of Hematology, Oncology and Transplantation, the University of Minnesota, Minneapolis, who is leading the pilot project. "Historically, chemotherapy has been given intravenously — first in the hospital, and then it moved to the clinic — but there were a lot of safety mechanisms in place that were all tied to physical presence in the infusion center."

The situation is very different with oral chemotherapy, he explained. "Once we started using oral chemotherapy at home, I would write a prescription and hand it to the patient, and that was it. Everything was invisible to us."

Mechanisms were put in place to help monitor patients receiving oral therapy, Greeno continued, such as having pharmacists check in with the patient. "But we really don't have that direct connection as we did in the clinic, when patients are treating themselves at home," he said.

Adherence can be challenging. For example, the regimen for capecitabine is complex. To complete one of eight cycles of chemotherapy, a patient must take four pills twice a day, with 2 weeks on therapy and 1 week off therapy.

Another problem that can arise is anxiety.

It can be frightening for patients not to have support when they are receiving chemotherapy, explained Greeno. "They are basically on their own at home, but this system gives them more of a connection to their doctors," he said.

So far, feedback has been very positive. "We were worried that patients would not want to do it, but they all think it's a great," Greeno said. "They no longer have to worry if they forgot their pill, like waking up at midnight and wondering whether or not they took it."

The digital system also allows providers and caregivers to find out about potential problems in real time. During the trial, the system notified the team that one of the patients had not taken her dose. When they subsequently checked up on her, she said that her "hands hurt and she couldn't open the bottle," Greeno explained.

"We quickly found out what the problem was and remedied it," he said. "We were not only able to find out that she had not taken her dose, but the reason for it."

The device not only monitors adherence but also measures patient activity and rest, as well as heart rate. "This enables us to get a better idea of what is happening with the patient in real time," he said.

Provides Info on Pill and Patients

The digital pill system consists of an ingestible sensor that is about the size of a grain of sand. It is placed inside a gel cap along with the active drug. The patient wears a sensor patch measuring about 1" × 3" on their torso. After the pill is swallowed, the sensor is activated when it reaches the stomach. It then sends a signal to the patch, which in turn sends a digital record to an app on the patient's mobile device. The record is also sent to the Proteus cloud, where it can be shared with designated providers and caregivers.

Although this is the first foray of the digital pill into chemotherapy, the technology itself is not brand new.

Scooter Plowman, MD, senior director of franchise development at Proteus Digital Health, explained that the sensor is already being used, either commercially or in clinical trials, in about 40 medications for the treatment of hypertension, hyperlipidemia, diabetes, hepatitis C infection, HIV, and tuberculosis.

"There isn't any oral therapeutic that it can't be used with," Plowman told Medscape Medical News. "Thousands of patients have been treated — over 180,000 patients have ingested the sensor to date."

In more than 60 clinical trials that have been conducted since 2004, the patch and sensor have been demonstrated to be accurate and safe. In one study that involved 20,993 ingestions in 412 study participants, there was a 97.3% detection rate of the ingestible sensor and 100% accuracy, with no false positive signals. Only four participants (1% of the cohort) reported experiencing nausea or vomiting, and during 6407 patch-use days among 492 volunteers, 61 individuals (12.4%) reported a self-limited rash around the sensor site.

The trials with various digital pills show that adherence rates are higher than are seen with standard therapy. "The digital drugs have an average adherence rate of 80%, while the literature shows that only about 50% of prescriptions are taken as directed," said Plowman. "This is a way to help physicians keep a closer eye on their patients and for the care to be more precise and personal."

So far, the company has produced products that combine an active FDA-approved drug with the sensor in a single capsule. Because they are separate components, they did not need to receive an additional approval from the regulatory agency.

However, one product involves a different technology, explained Plowman. The Abilify MyCite aripiprazole tablet, for use in the treatment of schizophrenia and bipolar disorder, was developed in collaboration with Otsuka Pharmaceuticals. It represents a kind of "next generation" of ingestible sensors, he said.

In this case, "the sensor is actually embedded in the pill," explained Plowman, "so it is different and required FDA review and approval, which was received in 2017."

The FDA noted that this was the first digital medicine system to be approved as a pharmaceutical. Thus, said Plowman, it can be prescribed like any other drug; previous regulatory clearance for the Proteus technology was obtained through the medical device pathway.

The Abilify MyCite system is not yet available commercially. Plowman explained that the delay is largely because the drug is the first of its kind, and it took several years to obtain FDA approval. "Part of the process now is also to establish a new payment model for it, so that has also been taking some time," he explained.

Next Moves

The company plans to expand digitalizing supportive medications and to develop products that cancer patients can use to manage side effects. A larger trial with digital capecitabine is also planned, Plowman said. Patients are currently being enrolled at two sites. The goal is to enroll 750 patients over 2 years.

"This is going to be a registry study, so it will be ongoing," he said. "And we want to use real-world data, which is more beneficial and enhances quality."

The focus will continue to be on the treatment of gastrointestinal cancers with capecitabine.

Approached for comment, William Blackstock, MD, chair of radiation oncology and program director of the Comprehensive Cancer Center at Wake Forest Baptist Health, Winston-Salem, North Carolina, commented that he was quite excited to read about this new technology.

"We are going to be seeing more and more cancer drugs moving to oral therapy," he told Medscape Medical News. "And you know patients don't like to disappoint their doctors. If you ask them if they took all their medicine, they'll tell you, 'Sure, of course I did.' And you never really know if that's true or not, because they don't want to disappoint you.

"I think this is a good way to tell if the therapy that we're prescribing is actually being taken by the patient," he said.

Blackstock also thinks that manufacturers should consider using this technology for new drugs in clinical trials. "You don't want a study to be negative because the patients weren't taking the drug and you just didn't know it," he said. "I worry about that. I've done studies with patient logs, and you have to just trust them."

He also noted that the population is getting older. "We need strategies to make sure that elderly individuals who are living independently are taking their medications as prescribed. So this technology will be a great help to family members. It has a lot of applications," he said.

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