It is estimated that nearly 75% of adults do not adhere to a prescribed pharmacologic regimen, including failure to fill new prescriptions, taking less than the prescribed dose, or discontinuing drug therapy without prior discussion with their physician. Long-term treatments for chronic illnesses often require strict patient medication adherence, yet only 51% of patients in the United States who are prescribed antihypertensive drugs adhere to the prescribed treatment. This number varies from 40–70% for patients taking antidepressants and greatly increases the risk of relapse. Patient nonadherence to a prescribed pharmacologic treatment can not only harm the patient, but also carries a significant financial burden. The total economic burden of medication nonadherence is estimated to be $100–300 billion annually including the cost of hospitalizations and emergency department visits that could have been prevented with proper adherence. In one study, the number of hospitalizations and emergency department visits related to chronic vascular diseases declined with increased adherence and the uptick in pharmacy costs were offset by the healthcare savings.
In addition to contributing to suboptimal treatment outcomes, medication nonadherence can also impact safety and efficacy data in clinical trials for investigational drugs. If a large trial with an outpatient population has variable adherence, the protocol-specified dose may be too low for efficacy or too high and toxic. In 2012, the Food and Drug Administration (FDA) guidance on clinical trials for human drugs and biological products encouraged the use of adherence prompts, alert systems, and counting pills or smart bottles to monitor medication adherence and encourage patient compliance. New technology in the form of smart pills and bottles could help in reducing nonadherence in both clinical trials and individual patient pharmacologic treatment plans.
Pill boxes are an inexpensive tool for improving patient adherence, but visual acuity and cognitive impairment are potential barriers in correctly filling the pill boxes or taking the daily required medications without reminders (particularly in the elderly). Real-time measurement is now possible with pill dispensers containing sensors to monitor adherence, provide reminders, and transmit data to patients, caretakers, and clinicians. One such smart pill bottle was invented by researchers at the University of Alabama in Huntsville and licensed to AdhereTech; it uses a sensor in the bottle to detect if the bottle has been opened and calculates the number of pills or liquid remaining in real-time. This data is then transmitted wirelessly from the bottle to computer servers and is analyzed for any missed doses or errors. If a patient skips a dose, the bottle notifies the patient or other approved individuals via on-bottle lights and chimes and an automated phone call or text message. The use of real-time data analysis can detect lengthy nonadherence and follow-up via a phone call or text message for information on the missed dose or doses. Their responses can be sent directly to live case managers for immediate interventions such as changing the dose or switching the patient to an alternate medication. The bottles are FDA-registered Class I medical devices and the AdhereTech data collection system is HIPAA-compliant. A pilot test is underway at the Walter Reed National Military Medical Center and will be tested in a 12-week randomized trial at Weill Cornell Medical College involving 70 HIV-positive patients with sub-optimal medication adherence.
The same sensor technology integrated into smart pill bottles is also being incorporated on a much smaller scale- the pills themselves. In 2012, Proteus Digital Health received FDA clearance for its ingestible sensor that can be integrated into tablets or capsules during pharmaceutical manufacturing. Less than 1mm square in size and comprised mainly of silicon, the sensor transmits a unique and private digital code to identify the medication, dose, and time of ingestion upon contact with stomach fluid. The stomach fluid acts as a power source to activate the sensor in transmitting the digital code to a battery-operated patch worn on the left side of the body just below the chest. Lastly, the patch sends the information to a Bluetooth-enabled device and a secured centralized database. Using the secure Helius application for smartphones, tablets, and computers, the information can be viewed by the patient or, with permission, to their caregivers or clinicians. The patch may be worn for up to one week; it also can detect and relay information on heart rate, physical activity, and inactivity. In 2010, Proteus announced a collaboration with Novartis to develop and commercialize products with the sensor in the field of organ transplantation with option rights for cardiovascular and oncology product applications, as well as rights to use the technologies in clinical trials for pharmaceutical product development. A 12-week open-label single-arm exploratory study of twenty kidney transplant patients in stable condition after an average of 6.0±5.0 years post-renal transplantation evaluated the sensor and patch accuracy vs. directly observed ingestions (DOI) in medication adherences and timing adherence. The patients were prescribed enteric-coated mycophenolate sodium (ECMPS) that included the sensor technology system. The sensor system reported a 100% detection accuracy rate over 34 directly observed ingestions, 99.4% in ECMPS that included the sensor, and 99.3% in detecting the ingestion of two ECMPS capsules taken simultaneously.
Improving patient medication adherence can be difficult if social and economic factors (age, race, sex, socioeconomic status), patient-related factors (knowledge, attitude, beliefs), condition and treatment-related factors (severity of the symptoms and disease, complexity of the medical regimen, duration of treatment, adverse effects), provider characteristics (communication skills, training, and resources), and settings (drug coverage, cost sharing of medication, and access to medication and clinical care) are barriers to drug therapy. Technology may not improve adherence if one or more of these are significant factors in which real-time monitoring is not the solution. The World Health Organization (WHO) recommendations for patient adherence to long-term treatments, including diet and/or lifestyle changes, include the need for clinicians to assess patient readiness to adhere to a therapeutic plan and provide guidance and support rather than blame if nonadherence occurs.
As the incidence of chronic illnesses continues to climb, medication adherence will become more important than ever in disease control and reducing healthcare-associated costs. Although technology may not resolve all issues linked to patient medication nonadherence, innovations utilizing sensors like the AdhereTech smart pill bottle and the Proteus sensor system could contribute to improved outcomes in pharmacologic treatments seen in clinical trials and patient therapies.