Telling Technology: Increasing Adherence, Tagging Triggers

In the United States, half of all chronic disease medications are not taken as prescribed.¹ Each year, this nonadherence causes 125,000 deaths; 10% of all hospitalizations²; and $105 billion in preventable costs.³ Long-term adherence is difficult to achieve, typically dropping after the first 6 months of treatment.⁴ Patients often improve adherence in the 5 days before and after a visit to their provider, but they have difficulty sustaining this “white-coat adherence.”⁵
 
Traditional adherence aids, such as pillboxes and blister packaging, help patients organize their medications by day and time. A 2015 systematic review and meta-analysis looked at 52 medication adherence studies employing either pillboxes or blister packaging. Results suggested that these methods significantly improve adherence: average adherence rates were 71% for treatment subjects and 63% for control subjects.⁶ However, there is still room for improvement and a role for new, high-tech devices. Effortlessly delivering real-time adherence data to patients, providers, and caregivers, these products provide daily accountability, facilitate adherence conversations, and predispose patients to more informed treatment decisions. New technologies can also address medications not included in pillboxes, such as inhalers and insulin pens.
 
Smart Containers
Pill bottles are receiving makeovers from companies such as New York-based AdhereTech (Table 1^7,8). When the technology-enhanced bottles are opened, sensors calculate the quantity of medication (tablets, capsules, or liquid) remaining and send the date, time, and dose taken to a portal for provider or researcher access. If patients miss a dose, lights and chimes on the bottle and an automated phone call or text message remind them to take their medication. The program asks patients for a reason why the dose was missed, analyzes responses, and refers patients to a case manager when appropriate, such as for reports of adverse events.⁷
 
Table 1: Smart Bottles: Advantages

Calculates amount of medication remaining May communicate automatically with health care team using Bluetooth technology Reminds patients when doses are due Asks patients to explain missed doses Gathers data to guide treatment decisions

^{Adapted from references 7 and 8.}

Another smart container under development is an in-home dispensing and reminder system designed by HAP Innovations of Durham, North Carolina. Patients plug in the machine and load a medication cartridge that has been prefilled by a local pharmacist. From there, medication dispensing and reminders are fully automated for patient convenience. The Bluetooth-enabled device also gathers data from medical devices in the home, adding these to an electronic health record that can be shared with family members, pharmacists, and other providers. Plans even include a screen to enable telemedicine meetings with physicians, pharmacists, and caregivers.⁸
 
Smart Pills
Ingestible sensors provide a new way to measure adherence directly, something a container simply cannot do. Proteus Digital Health, based in Redwood City, California, is pioneering this new technology. In July 2015, the FDA approved the company’s co-encapsulated sensor for measuring adherence. Then, in September 2015, the FDA accepted the first-ever Digital Medicine New Drug Application, combining Proteus’ sensor with Otsuka’s Abilify (aripiprazole) into a single tablet.⁹ No bigger than a grain of sand, this tiny silicone microchip is covered in thin layers of magnesium and copper. When the chip reaches electrolytes in the stomach, an adhesive-backed monitor worn on the patient’s torso detects a specific electrical current. The Bluetooth-enabled monitor transmits the date, time, and medication name to a smartphone app, and on to patient-approved caregivers and providers through a secure Web portal. The monitor can record other data, too (Table 2^9-11). Algorithms can even determine when patients are sleeping. This enables researchers to gather detailed data on medications’ physiologic effects over long periods.¹⁰
 
Table 2: Smart Pills: Data Gathering

Smart pills can gather the following information: Date, time, and name of medication taken Activity levels at frequent intervals Body position Heart rate Respiratory rate Steps Temperature

^{Adapted from references 9-11.}

A pilot study on 5 patients with metformin-treated type 2 diabetes showed how providers could use this system to analyze adherence patterns. In one patient, sleep disturbances were highly predictive of missed doses the next day. For him, resolving sleep problems could be key to improving metformin adherence.¹¹ Studies support this system's accuracy and safety. A 12-week study on 20 patients taking co-encapsulated sensors with medication reported a detection accuracy of 100% after 34 directly observed ingestions. Over 2377 prescribed ingestions, the system was 99.3% accurate at detecting the consumption of 2 capsules taken together. No serious safety concerns were attributed to the sensor system. The tiny sensor is excreted in feces, and the trace amounts of copper and magnesium absorbed are minimal compared with recommended daily allowances. However, some patients react to the monitor’s adhesive backing, and 2 subjects quit the study due to skin rash.¹⁰