Electronic measurement of medication adherence.

524492 research-article2014

WJNXXX10.1177/0193945914524492Western Journal of Nursing ResearchPark et al.

Research Report

Electronic Measurement of Medication Adherence

Western Journal of Nursing Research 2015, Vol. 37(1) 28–49 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0193945914524492 wjn.sagepub.com

Linda G. Park1,2, Jill Howie-Esquivel2, and Kathleen Dracup2

Abstract The measurement of medication adherence is important in both clinical practice and research settings to offer effective medical therapy, improve clinical outcomes, and determine the efficacy of therapy. The aims of this article are to (a) present an overview of current and developing electronic methods of medication measurement, (b) explore the advantages and disadvantages to each approach, and (c) discuss the implications of using electronic monitoring devices for clinical practice and research. A comprehensive review of electronic forms of medication measurement was performed. A description of each method is presented including oral medication monitors, personal electronic devices, electronic blisters, wirelessly observed therapy, inhaled medication monitors, mobile phones, video/photo-assisted observation, and electronic health records. Familiarity with using electronic devices and advances in technology will continue to develop and influence the measurement of medication adherence. Keywords medication, medication adherence, measurement, electronic monitoring device Medication nonadherence is a major global challenge as more than half of individuals with chronic diseases do not take any or all of their medications 1San

Francisco VA Medical Center, San Francisco, USA of California, San Francisco, USA

2University

Corresponding Author: Linda G. Park, San Francisco VA Medical Center, University of California, San Francisco, Division of Geriatrics, 4150 Clement St. 181G, San Francisco, CA 94121, USA. Email: [email protected]

Downloaded from wjn.sagepub.com at PURDUE UNIV LIBRARY TSS on May 22, 2015

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correctly (Haynes, McDonald, & Garg, 2002; World Health Organization [WHO], 2003). In developing countries with limited resources and access to health care, medication nonadherence is assumed to have even greater magnitude and impact (WHO, 2003). Medication nonadherence is a major barrier to achieving optimal health as demonstrated by increased rates of emergency department visits, hospitalizations, morbidity, and mortality, which are attributed to intentional or nonintentional medication nonadherence (Butler, Davis, Johnson, & Gardner, 2011; Smith et al., 2006). The measurement of medication adherence is important in both clinical practice and research settings. In clinical practice, accurate measurement of patient medication administration will enable health care providers to evaluate clinical outcomes more accurately. In research settings, accurate assessment of medication adherence will lead to conclusive data about the efficacy of the therapy or intervention being tested. Nurses can address the barriers for medication adherence and can be integral change agents in promoting innovative medication measurement in clinical practice and research that is tailored to specific interventions and individual patient groups (Schlenk, Bernardo, Organist, Klem, & Engberg, 2008; Van Camp, Van Rompaey, & Elseviers, 2013). Measurement of medication adherence has traditionally included acquiring data on patterns of medication use from sources such as patient selfreport (i.e., interviews, diaries, questionnaires). Direct observation and pill counts have been other popular methods to record adherence. Clinical signs can be followed to track improvement of certain medical conditions (i.e., blood pressure as a measure for hypertension or pedal edema as a sign of hypervolemia). A rarely used form of medication adherence measurement is the addition of metabolites to medications to prove ingestion of medications (e.g., low doses of digoxin, phenobarbital, bromide, and riboflavin; Braam, Van Uum, Lenders, & Thien, 2008; Steel, Nwokike, & Joshi, 2007). Biomarkers provide vital clinical information about medication adherence (Foundation for the National Institutes of Health, 2012). Biomarkers are defined as characteristics that are objectively measured as indicators of normal biologic, pathogenic, or pharmacologic processes to therapeutic intervention (Foundation for the National Institutes of Health, 2012). Biomarkers include laboratory tests that assess clinical status and management of chronic disease (e.g., cholesterol levels and viral loads) or other physical samples that test for direct concentration levels of medications (e.g., in blood, urine, or hair). A preferred approach to achieve accurate measurement is to use multiple direct and indirect sources including use of biomarkers and self-report (Osterberg & Blaschke, 2005). Beyond the traditional sources of measuring adherence, advancements in technology have added to the breadth of methods one can employ in assessing


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adherence. Electronic monitoring is under rapid development through the use of electronic sensors, mobile, and wireless technologies and potentially can provide a rapid, organized form of collecting, storing, and analyzing adherence patterns with feedback to the patient, clinician, and researcher to enhance medication adherence behaviors. Electronic devices have been available for use in clinical and research settings in the form of electronic pill containers, medication blisters, and inhalers and continue to be popular forms of measurement. Other current and developing methods include personal home-based electronic devices, wirelessly observed therapy (WOT) by ingestible sensors, mobile phones, videoand photo-assisted observation, and electronic health records (EHRs). The current methods of electronic measurement are summarized in Table 1. Although the use of electronic methods to measure medication adherence has grown, there is still a need to establish their functional capabilities in clinical and research settings (Ingerski, Hente, Modi, & Hommel, 2011).

Purpose The aims of this article are to (a) present an overview of current and developing electronic methods of measuring medication adherence, (b) explore the advantages and disadvantages of each approach, and (c) discuss the implications of using electronic devices for clinical practice and research. Although the primary aim is to present a review of electronic measurement methods, these methods may inherently enhance medication adherence through the monitoring effect. In the clinical setting, modified forms of these methods can be considered for the enhancement of medication adherence in the future.

Method A literature search was conducted using PubMed and Cumulative Index to Nursing and Allied Health (CINAHL) to identify relevant articles using “medication adherence” in combination with the following terms: electronic, monitor, electronic monitoring, electronic measurement, Medication Event Monitoring System, pill organizer, electronic blister, wirelessly observed therapy, ingestible sensor, electronic inhaler, mobile health, video, and electronic health records. An Internet search (i.e., Google) was conducted using the above terms to obtain the most current information on industry websites and to access additional articles. Bibliographies of relevant articles were cross-referenced when applicable. Out of 470 titles that were reviewed and 173 abstracts that were screened, 50 articles were reviewed in addition to approximately 27 websites. English-written articles were selected if they



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Wirelessly observed therapy

Electronic blister

Personal device

Oral pill organizer

Oral pill bottle

Type of Electronic Monitoring Device

An ingestible electronic sensor that is attached to a tablet to track use with a patch monitor. The data on the monitor are sent wirelessly to a designated mobile phone then to a secure data server.

Electronic pill bottles with sensors on the caps that digitally records opening of a bottle. Data from caps are downloaded to a computer via a scanner. Electronic pill organizer with sensors that digitally records opening of the lid of each compartment. Some systems provide medication reminder alerts. Devices used for personal home use and available solely for consumer use. Provides medication reminder alerts. Electronic labels affixed to standard paper blister packages or blister pack. Some systems hold blisters, while others have radio-frequency enabled self-adhesive labels.

Description

Table 1. Type and Description of Electronic Monitoring Devices.

(continued)

Intelligent Drug Administration System (IDAS; Bang & Olufsen Medicom, Struer, Denmark) Helping Hand (Bang & Olufsen Medicom, Struer, Denmark) Smart Blisters (Qolpac BV, Eindhoven, the Netherlands) Med-ic ECM (Information Mediary Corporation, Ontario, Canada) Cerepak (MeadWestvaco, Virginia, United States) Helius (Proteus Digital Health, Redwood City, California)

Wisepill (Wisepill Technologies, South Africa) MedSignals (San Antonio, Texas) Med-eMonitor (Rockville, Maryland) GlowCaps (Vitality, Los Angeles, California)

MEMS (MeadWestvaco, Virginia, United States) eCap (Information Mediary Corp., Canada)

Examples

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Text messaging and applications using mobile phones to self-report use of medications. Patients can text responses to medication reminder alerts or use an application to monitor medication use. Patients record themselves taking medications via video or mobile phone in place of face-to-face visits. Real-time interactive video or date/timestamped pictures can be recorded. Medication records available for universal use to monitor medication use while patients are in their network system.

Mobile phones

Electronic health records

Video/photoassisted

Electronic inhaler or nebulizer that digitally records use. Other smaller electronic devices can attach to an existing inhaler.

Description

Inhaled monitor

Type of Electronic Monitoring Device

Table 1. (continued)

Veterans Administration, Kaiser Permanente

Not applicable

DOSER (MEDITRACK Products, Easton, Massachusetts) MDILog (Westmed Technologies Inc., Englewood, Colorado) Smartinhaler (Nexus 6, Auckland, New Zealand) Chronolog (Forefront Technologies Inc., Lakewood, Colorado) Halolite (Profile Therapeutics PLC, Bognor Regis, England) Propeller (Propeller Health, San Francisco, California) All wireless carriers are text-capable Smart phones carry applications

Examples


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Advantages User-friendly Wide access Real-time monitoring Provides patterns of use Well accepted by patients Medication reminders Ubiquitous use Uses wireless technology Does not require patient participation Cost saving compared with direct observation More convenient than direct observation Disadvantages Potentially costly Requires software and analysis Potential software and equipment problems Use does not necessarily reflect ingestion of medication Efficacy not established X X X X

X X X X X

X X X X

X X

X

X X X X X

X X X X

X

X

X

X X X X

X

X X

X

Personal Electronic Device Blister

X

Oral Pill Monitor Organizer

X

X X X

X X X X

X

X X X

X

X X

X

X

X

X X

(continued)

X X X

X X X

Video/photoElectronic Assisted Health records

X

X X X X X X X X

Mobile Phones

X

X

X X X

X

Inhaled Monitor

X

X

X X

Wirelessly Observed therapy

Table 2. Advantages and Disadvantages of Electronic Monitoring Devices.

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X X

X

X X

X

X

Oral Pill Monitor Organizer

X

X

X

X

X

X

X

Personal Electronic Device Blister

X

X

X

X

Wirelessly Observed therapy

X

Inhaled Monitor

X

X X

Mobile Phones

X

X

X

X

X

X

Video/photoElectronic Assisted Health records

Note. There are a variety of brands within the methods presented. The advantages/disadvantages may be variable for pill organizers, electronic blisters, and inhaled monitors.

Potential to produce “alarm effect” Older patients may be resistant May be challenging with complex medication regimens Potential privacy issues with detailed medication behavior patterns May not include the most updated information Requires maintenance of video or other equipment Requires frequent recording by patient and monitoring by staff Requires filling of bottles/organizers/blisters Skin irritation

Table 2. (continued)

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addressed electronic measures of medication adherence. Articles were excluded if adherence was measured using a method other than an electronic source. The electronic devices were selected for this article through a building process of reviewing articles and websites to determine current and developing electronic forms of monitoring medication adherence due to the expanding availability of these products.

Electronic Monitoring Modalities Oral medication monitors. A popular form of an oral medication monitor is the Medication Events Monitoring System (MEMS), which is a computerized monitoring system that includes a computer chip located inside a pill bottle cap. The MEMS allows data, including the date and time of bottle opening, to be downloaded to a computer by using a MEMS reader (Ailinger, Black, & Lima-Garcia, 2008). The MEMS reader is a small device that serves as a platform to transmit data from the cap to the computer (Ailinger et al., 2008). There are two options with MEMS, including TrackCap and SmartCap. In addition to the microchip feature of the TrackCap, the SmartCap features a display on the cap that shows the number of doses taken in the past 24 hours and the hours elapsed since last dosing (MeadWestvaco Corporation, 2013). This system is a common objective method of measuring medication adherence, and it is generally well accepted by patients (Hamilton, 2003; Schwed et al., 1999). One of the advantages of MEMS is the ability to identify patterns of nonadherence such as the “toothbrush effect” or “white-coat adherence,” which pertain to patients improving their medication taking behavior in the 10 days preceding an appointment with their health care provider (Schwed et al., 1999). Another electronic pill bottle that has been reported in the literature is eCap (Ayoade & Oladipo, 2012). This device is very similar to MEMS but also offers 12 optional daily beeping/flashing reminders that are matched to patients’ dosing schedules (Ayoade & Oladipo, 2012). Similar to MEMS, the stored data in the eCap can be downloaded to a computer via a scanner. The eCap system is available for use in clinical trials and commercial packaging (Ayoade & Oladipo, 2012). Several electronic medication organizers for patients taking multiple medications are also available that provide real-time data on adherence. Wisepill was one of the first devices used in adherence research and included a twocompartment container storing approximately 30 large pills or 60 small pills and used real-time cellular signals on a web-based server (Haberer et al., 2010). WisePill, otherwise known as Real-Time Medication Monitoring (RTMM), is an innovative system that combines electronic monitoring with


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text message reminders (Vervloet et al., 2012). The RTMM system has a unique feature to remind patients to take medications through text messages only if they forget to take their pills given the real-time registration of medication use (Vervloet et al., 2012). SIMpill has similar characteristics (SIMpill, 2012). MedTracker is another system that had early experience using a 7-day drug store pillbox with Bluetooth technology (Hayes, Hunt, Adami, & Kaye, 2006). Another organizer is MedSignals, which is a device that consists of four plastic containers and stores data from every lid opening, creating a record that is time-stamped and documented in real time (MedSignals, 2012). Since 2008, data have been transferred through a telephone line, but a new model allows mobile phones with Bluetooth technology to monitor individuals remotely and immediately transfer the data to the patients’ personal profiles on the Internet (MedSignals, 2012). MedSignals has an option to remind patients and caregivers about medication schedules through personalized alerts via email, text, fax, customized electronic medical records connections, or automated phone calls in various languages (MedSignals, 2012). Settings are displayed for each plastic container, so clinicians and researchers are able to remotely monitor medication use (MedSignals, 2012). MedSignals is tailored for health care providers, researchers, home health agencies, and caregivers and is available for consumer purchase unlike MEMS, which is unavailable for personal use. The Med-eMonitor is an electronic pill organizer that stores medications and electronically records the time and date of every opening of five compartments (Haberer et al., 2012). Adherence data are stored in memory and downloaded to a secure website during pre-set time windows through a modem cradle connected to a telephone line (Haberer et al., 2012). The device prompts users to take their medication by sounding a chime and using a liquid crystal display (LCD) to provide instructions on medication use and other customized information (Haberer et al., 2012). RTMM is an innovative system that combines electronic monitoring with text message reminders (Vervloet et al., 2012). The RTMM system has a unique feature to remind patients to take medications through text messages only if they forget to take their pills given the real-time registration of medication use (Vervloet et al., 2012). SIMpill has similar characteristics (SIMpill, 2012). The benefits of the electronic oral medication monitors (single bottles or organizers) cannot be discounted as they document drug holidays (missing doses for at least two consecutive days) or overuse of medication (Schwed et al., 1999). However, disadvantages of the electronic oral medication monitors include the inability to confirm how many pills were removed from the


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bottles and containers or if the pills were actually ingested. Electronic oral medications monitors also have potential mechanical problems. For example, problems reported with the MEMS device include equipment, battery, or actuator switch failure, as well as patients damaging the cap or placing it near a microwave oven (Hamilton, 2003). Other issues with electronic bottles and organizers include the need to carry the devices for medications that require more than once daily dosing (Hamilton, 2003). In addition, patients may resist using a single pill bottle device because it is necessary to use individual bottles instead of the convenience of their pill organizer. Another consideration is the time and ability to download the data from electronic sensors to the computer if data are not transmitted real time. Overall, the clinical benefit of the electronic measures may be limited by the high cost of the materials and software. Personal electronic devices. In contrast to other oral medication monitors that have been predominately reserved for research purposes (except MedSignals), personal home monitors have become available for consumer use. Advancements in technology are allowing patients, caregivers, and clinicians to make strides with adherence to self-administration of medication. For example, GlowCap is a digital pill bottle that sends messages via lights, sounds, music, and automated phone calls and is an excellent alternative to traditional pill containers and reminder systems for home use (Vitality, 2010). An electronic chip on the pill cap monitors when the bottle is opened and wirelessly sends alerts through a mobile network to individuals or their caregivers. GlowCaps also have a button that uses mobile connectivity to contact the patient’s pharmacy for refills then triggers an automatic callback to confirm the request (Vitality, 2010). The use of GlowCaps generates a weekly email summary with personalized information that can be shared with a “health buddy,” and compliance reports are mailed to designated health care providers monthly (Vitality, 2010). Thus, these devices help build a network of social support from caregivers and health care providers. Testing is currently underway to introduce another form of a personal electronic pill device referred to as GlowPack. The GlowPack is a resealable pouch that holds blister packs, inhalers, injectable solutions, liquid medication, and topical ointments that works similar to the GlowCap (Vitality, 2010). As GlowCaps have only been available since early 2013, it is premature to discuss the willingness of consumers to purchase and use the medication devices. At the current time, GlowCaps are only available for purchase through one pharmacy chain and are not covered by insurance, which may militate against their widespread use. However, the personal investment may


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help engage patients and caregivers in using the device to promote medication adherence. In addition, monthly service plans allow for connectivity to an assigned wireless network but incur additional costs to using the device. With the rapid development of technology and research, it is likely that personal electronic devices will gain greater acceptance and popularity as our society becomes more adept to electronic and wireless forms of self-monitoring. Electronic blisters. Electronic blister packs have been used in research settings to monitor adherence. The Intelligent Drug Administration System (IDAS II) is a customized electronic device that accommodates specific blister packs and can record the date and hour of the removal of a drug dose from the blister (Santschi, Wuerzner, Schneider, Bugnon, & Burnier, 2007). The Helping Hand is another type that is a flat, slightly arched blister cardholder and resembles a telephone handset. Programmable visual and audible alerts can be sent as reminders to take medications (De Bleser et al., 2010). Another version is an electronic blister sheet that can contain 28 medication tablets, but a separate device is needed for each medication (Yamada & Nakashima, 2003). The device connects to a personal computer and a printer to set alarms and provides a record of when the device button was pushed (Yamada & Nakashima, 2003). Smart Blisters and the Med-ic ECM are radio-frequency enabled selfadhesive labels that can be affixed to existing standard medication blister packages and have been tested by researchers with promising results (van Onzenoort et al., 2012). Unlike the IDAS, the Smart Blister offers the advantage of not requiring the development of a dedicated system or alteration of the blister pack (van Onzenoort et al., 2012). This medication monitoring system uses wireless data transmission and Internet server storage capabilities to maintain data (van Onzenoort et al., 2012). Another type of electronic blister package is Cerepak, which is portable, disposable, and available in multiple sizes, making it convenient for patients and professionals (MeadWestvaco Corporation, 2013). In addition, the carton is customizable with branding, educational messages, and dosing instructions (MeadWestvaco Corporation, 2013). An advantage to electronic blisters is that blister packaging is more common in some countries than in others (van Onzenoort et al., 2012). More precise and clinically meaningful insights into patients’ medication patterns can be determined in comparison with MEMS where it is unclear how many pills are removed from the bottle (van Onzenoort et al., 2012). Similar to oral medication monitors, high cost and an inability to confirm ingestion of medications are pertinent disadvantages to this method of adherence assessment. In addition,


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using blisters may be challenging for patients who have a complex medication regimen and use pill organizers. Mechanical failures are also a potential disadvantage to accurate medication monitoring (van Onzenoort et al., 2012). WOT. WOT is the newest mode of medication measurement using an ingestible electronic sensor. The first system that was developed and approved by the Federal Drug Administration in 2012 includes (a) an ingestible sensor (Ingestion Event MarkerTM [IEM]) that is attached to a tablet to track use and (b) an ambulatory, battery-operated monitor that is applied as a skin patch that detects an ingested sensor (DiCarlo, 2012). The IEM is a very small (1.0 × 1.0 × 0.33 mm) device that rests in the center of an edible, cellulose-based 5-mm disk (DiCarlo, 2012). After ingestion, the sensor separates from the medication, is activated by gastric fluid, and communicates with the monitor that is worn on the user’s torso (Au-Yeung & DiCarlo, 2012). The information stored in the monitor is encrypted and sent wirelessly using Bluetooth technology to a designated mobile phone with communication to a secure data server (Au-Yeung & DiCarlo, 2012; DiCarlo, 2012). The system provides real-time confirmation of the type, dose, date, and time of medication ingestion but also monitors and records biometric and behavioral data such as heart rate and activity (DiCarlo, 2012). The system can aggregate these biometric and behavioral data with other data such as blood pressure, creatinine, glucose, and weight from other electronic devices and incorporate data entered by individuals such as symptoms or self-assessments (DiCarlo, 2012). The externally worn adhesive monitor allows wear for up to 7 days during all daily activities including bathing and swimming (DiCarlo, 2012). In settings where direct observed therapy (DOT) has been used such as tuberculosis treatment, health workers are able to use WOT as an alternative to confirm objective medication ingestion (Au-Yeung & DiCarlo, 2012). Using WOT allows health workers to manage a large number of patients remotely to verify completion of treatment or to provide more intensive management (e.g., phone calls and/or outreach visits) for nonadherent individuals (Au-Yeung & DiCarlo, 2012). Using WOT reduces the need for patients to travel to a designated location for DOT, and thereby promotes greater privacy, reduces travel expenses, and does not require patients to take time off from work (Au-Yeung & DiCarlo, 2012). Many tuberculosis patients who are migrant workers in countries such as China and Mexico may benefit the most from WOT (Au-Yeung & DiCarlo, 2012). A direct cost comparison of WOT versus standard of care DOT with 7-day and 3-day DOT showed major cost benefits to WOT with costs comparable with 36% of 7-day DOT and 71% of 3-day DOT in public health facilities’ cost-to-treat (Au-Yeung & DiCarlo, 2012). The cost-to-be-treated with WOT were estimated to be 4% of 7-day


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DOT and 8% of 3-day DOT (Au-Yeung & DiCarlo, 2012). Despite these benefits, the WOT method is a novel form of medication monitoring, and its feasibility and acceptability in clinical and research settings is still being established. Adverse, minor patient experiences have included a skin rash with application of the patch and diarrhea (Eisenberger et al., 2013). Inhaled medication monitors. Several electronic monitoring mechanisms are available for metered dose inhalers (MDIs) and nebulizers. Examples of electronic MDIs include the DOSER, MDI Chronolog, MDILog, and Smartinhaler, while the Nebulizer Chronolog and Halolite are examples of nebulizers that electronically monitor use (Asthma and Allergy Foundation of America [AAFA], 2010; Ingerski et al., 2011; Quittner, Modi, Lemanek, Ievers-Landis, & Rapoff, 2008). The DOSER is an electronic MDI with a microchip that displays the number of inhalations taken within a 30-day period (AAFA, 2010). The SmartInhaler contains a microprocessor to record adherence with optional audiovisual reminders (i.e., emitting different levels of light and sound; AAFA, 2010). The MDILog and DPILog (dry powder inhalers) are more sophisticated devices that can monitor more than 1,000 actuations and are downloadable by the patient, caregiver, and clinician for viewing (AAFA, 2010). The microchip monitors both actuation and inhalation from aerosol and dry powder devices, and downloaded information allows clinicians to make more informed treatment decisions relative to inhaler adherence (AAFA, 2010). Another electronic form of monitoring is the Propeller sensor, which is a small device that attaches to the top of an existing inhaler (Propeller Health, 2013). The data are shared with the patient and clinician, so that feedback is given and treatment can be adjusted with customizable alerts to providers if a patient’s condition worsens (Propeller Health, 2013). Electronic inhaled medication monitors are able to detect the major limitation of “dumping” that may occur with inhaled medications (Ingerski et al., 2011). “Dumping” is the act of discarding unused medications before they are checked for adherence and is a phenomenon noted by several investigators who reported 15% of the control group dumped more than 100 actuations of the inhaler’s contents in a 3-hour period (Nides et al., 1993). In contrast, dumping was not found among the treatment group that received feedback about their inhaler use and was aware that their adherence patterns were being monitored (Nides et al., 1993). Similar to other electronic monitors, equipment failure and inability to confirm ingestion of medications are disadvantages associated with inhaled monitors (Ingerski et al., 2011). Other disadvantages are similar to oral medication monitors such as additional costs and time with using the equipment, software, and personnel along with potential mechanical failures.


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Mobile phones. Researchers are currently investigating the use of mobile phones to assess adherence to medications through this electronic form of self-report (Williams, Amico, Bova, & Womack, 2013). Given the popularity of mobile phones, intervention studies support that this modality may be feasible and effective in monitoring and promoting adherence in managing acute and chronic diseases (Cole-Lewis & Kershaw, 2010; de Jongh, GurolUrganci, Vodopivec-Jamsek, Car, & Atun, 2012; Wei, Hollin, & Kachnowski, 2011). Text messaging interventions using short message service (SMS) have been most widely applied. Few investigators have designed or tested interventions using a mobile phone application to assess medication adherence, but there will undoubtedly be more published studies available over time (Hayakawa et al., 2013; McGillicuddy et al., 2013; Meltzer, Kelley, & Hovell, 2008). Text message responses by a patient can be a convenient and engaging mechanism to monitor adherence patterns. Once a patient has responded to a reminder alert to take medications or an application is used, two-way messaging can document medication use, although responses from patients may not reflect actual medication taking behavior. This self-reported electronic medication diary may be a viable way to assess medication adherence, particularly when strict adherence is required (e.g., high-risk HIV populations and patients following organ transplant). The potential for mobile phone use in health care has not been well defined and remains a tremendous opportunity for future research, especially for patients with chronic diseases requiring lifelong medication adherence for optimal outcomes. In the future, further integration of mobile phones with EHRs can support communication between patients and their health care providers. Disadvantages of using mobile phones may be deterioration of interest as the novelty of monitoring adherence wanes over time given the rapidly evolving nature of technology. Factors that maintain engagement of participants remain unknown and serve as important gaps in research. The long-term impact of mobile health interventions is needed to document the efficacy and sustainability of these interventions on medication management. Individuals who are less technically inclined such as older adults may have difficulty using mobile phones for medication monitoring due to unfamiliarity with text messaging or applications, difficulty with fine motor skills, and resistance to using mobile phones for the purpose of monitoring. Video- and photo-assisted observation. Researchers have piloted the use of mobile DOT by having tuberculosis patients in Kenya transmit daily video recordings via mobile phones of medication self-administration (Hoffman et al., 2010). Using mobile health technology may be a substitute for face-to-face visits with


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health care workers in remote areas where the incidence of tuberculosis and HIV/AIDS is high and medication adherence levels are suboptimal (Hoffman et al., 2010). Video-assisted methods to measure adherence may be most valuable in regions where patients would be required to travel long distances to meet with health care providers for a short period of time for the purpose of monitoring treatment. Another innovative way to measure adherence is to have patients take pictures of medications prior to self-administration with mobile phones (Galloway, Coyle, Guillén, Flower, & Mendelson, 2011). Mobile technology such as the mobile phone is likely to influence medication adherence measurement in the future due to its ubiquitous use, particularly in developing countries. Video- and photo-assisted observation can significantly reduce costs of personnel resources; however, this mode of adherence measurement requires regular surveillance and communication with patients. This method requires dependable wireless services and more significant patient participation than other forms of adherence measurement. EHRs. Maximizing the potential of EHRs and pharmacy records can be a valuable way to measure medication adherence and maintain a permanent history of medication use. Pharmacy databases are increasingly popular forms of assessing medication use and can be used in conjunction with other monitoring systems (Vollmer et al., 2012). The expanded development of EHR such as electronic prescribing (Bosworth et al., 2011) can promote communication on medication information between health care providers, hospital systems, pharmacies, and patients. Improving interdisciplinary communication through an integrated EHR will be a critical step in improving the current state of adherence and optimizing the clinical value it can bring to patients. The current system must transition from an organization-specific EHR that stores health records to one that can seamlessly transfer valuable medication information to a broader network of providers and patients. Data that are available through pharmacy records are limited to the dates the medication was dispensed, which may not reflect actual medication administered (Jentzsch & Camargos, 2008). In addition, patients may obtain medications through other pharmacies, so records may be incomplete. Historically, refill records have been restricted to health care providers in closed clinical settings such as large health organizations (e.g., Veterans Administration and Kaiser Permanente), although some large pharmaceutical companies are reporting patterns of medication refills to providers. Open communication between health care providers and pharmaceutical companies needs to be


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developed and strengthened to use pharmacy records as a viable source of measuring medication use. Dependency on the health care team to accurately input data and for patients to communicate any changes that have been made outside the system is also a potential disadvantage to this mode of adherence measurement.

Discussion This review of electronic monitoring devices for medication adherence has numerous implications for clinical practice. The electronic methods that have been described, including oral medication monitors, personal electronic devices, electronic blisters, WOT, inhaled medication monitors, mobile phones, video/photo-assisted observation, and EHRs, can provide resources for clinicians to monitor patients by innovative and multifaceted methods. Medication monitoring may be most critical in patient populations with a history of organ transplant, HIV, and tuberculosis due to the public health implications. Electronic monitoring may begin in the inpatient setting and continued through outpatient clinics and home health services, so a variety of clinicians will need to be adept with these devices (e.g., MedSignals pill organizer). There is a growing need for an expanded interdisciplinary collaboration of nurses, physicians, pharmacists, engineers, computer scientists, and industry to implement these novel forms of medication measurement (e.g., mobile phone or wireless technology) in a safe, effective, and patientcentered manner. In the clinical setting, strategies to promote the use of electronic monitors will involve the development of more clinician- and patient-friendly methods of monitoring and evaluating adherence. A user-friendly interface that requires minimal technical expertise and promotes time efficiency is essential to bring the issue of medication adherence measurement to the forefront of clinical encounters as opposed to restricting it to research settings. The primary goal of accurately monitoring medication use will be achieved by a collaborative effort between patients and caregivers through effective communication in the clinical setting. Providing feedback about medication use through these monitoring devices may motivate patients to modify behavior (Eisenberger et al., 2013). The use of electronic devices can facilitate a dialogue between the patient and the medical team regarding medication adherence based on the objective assessment of medication intake (Eisenberger et al., 2013). There is a need to make meaningful connections to clinical outcomes after distribution of prescriptions but a radical transformation is needed within the nursing, medical, and pharmacy communities to support surveillance of medication adherence. User-friendly devices that


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engage patients and promote communication with clinicians are now available and include personal electronic devices, WOT, inhaled medication monitors, mobile phones, and video/photo-assisted observation. Changes in health policies may be required to keep prescribers and pharmacies more accountable to monitor adherence. This review of electronic monitoring devices also has implications for research. Abundant opportunities are available as electronic methods for measuring medication adherence are developing rapidly. A mixed-methods approach with quantitative and qualitative research involving patient feedback will be valuable as patient participation will be key to determining the efficacy of these methods to measure adherence accurately. Another prerequisite to successful measurement of medication adherence is patient participation with electronic devices. Understanding factors that motivate patients to change behavior through theoretical models will also influence the success of electronic monitoring systems. Due to the novel nature of many of these methods, there is limited research with long-term studies establishing efficacy and patient satisfaction with individual methods (e.g., personal electronic devices, WOT, video/photo-assisted observation) although MEMS has been widely used. Comparative effectiveness studies may also be helpful in comparing modalities. Finally, researchers must also consider patient security as a priority with some methods of monitoring that may be viewed as more intrusive such as personal electronic devices that can involve a caregiver, mobile phone text messages and applications, and video/photo-assisted observation. Establishing a secure process to share data from EHR, which is the least intrusive of all methods, across a network of providers and pharmacies also remains an opportunity. Removing barriers to using electronic monitors effectively needs to be considered. For example, consideration of removing technical obstacles with electronic devices or patient discomfort (e.g., skin rash from sensors) should be made (Eisenberger et al., 2013). In addition, as electronic methods are more costly than traditional methods of self-report, their use may be limited in both clinical practice and research. As the efficacy and popularity of electronic devices to accurately measure medication adherence become more apparent, it is hopeful that these systems will be less cost-prohibitive. Costs can be contained by better pricing from manufacturers or through subsidies by stakeholders (e.g., insurance companies, health care systems). Although a variety of electronic methods of medication measurement are currently available and even more are in development, other traditional methods of measuring medication adherence will remain important in both clinical practice and research. The most widely used techniques for monitoring adherence in research trials are pill counts and medication diaries; however,


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regular monitoring is rare in the clinical setting (Purohit & Purohit, 2009). Electronic monitoring devices are most suitable in research settings (except personal devices), although most developed methods can be used in clinical settings. However, electronic monitoring demands a considerable amount of technology and staff resources, so feasibility in the clinical setting requires further exploration. Multiple methods of measurement can corroborate adherence behaviors (Osterberg & Blaschke, 2005). For example, a text messaging intervention using multiple measurement tools such as a self-reported questionnaire, MEMS, and text responses from patients found that all three groups had similar improvement in self-reported adherence from baseline to followup, while there were significant group differences detected only by MEMS and text responses (Park, Howie-Esquivel, Chung, & Dracup, 2014). Using a more objective form of adherence such as MEMS is useful to determine adherence patterns; however, other forms of measurement such as self-report provide important information, so that appropriate interventions can be implemented. Future trends in medication measurement include use of electronic devices with remote monitoring that allow instant feedback on medication adherence for patients, caregivers, clinicians, and researchers. More innovative forms of measurement including a combination of forms that have been reviewed will likely become available. Researchers have already combined the use of mobile phone technology with electronic blisters and ingestible sensors to monitor adherence through mobile phones (Brath et al., 2013). The rapid integration of technology with daily living through real-time monitoring and Bluetooth technology will continue to advance and reshape the measurement of medication adherence. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

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