The document discusses medication non-adherence, which is a major problem that impacts health and costs the healthcare system billions annually. It describes various technologies that have been developed to help patients better manage and adhere to their medication schedules, ranging from basic pillboxes and reminders to more advanced automated dispensers and sensors. The document recommends pilot studies be conducted to evaluate the real-world effectiveness of different medication adherence technologies in improving patient outcomes beyond standard discharge instructions alone.

1. Medication Adherence
Enabling Technologies
January 18, 2016 (revised from May 7, 2009 version)
Michelle Y. Williams, RN, MSN, PhD candidate
TECHNOLOGY BRIEF

2. TECHNOLOGY WHITE PAPER MEDICATION ADHERENCE TECHNOLOGIES
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Executive Summary
The inability to achieve medication adherence, also known as medication
compliance and concordance, is a multifaceted problem that imperils the
health of individuals and populations, and hamstrings the efficiency of the
health care system at large. Its reach extends to care in the home, clinic,
hospital, networked health care system, and beyond.
According to the American Heart Association (AHA), the #1 problem in
treating illness today is the failure of patients to take their prescribed
medications correctly.1
Ernst and Grizzle (2001) found that prescription
medication nonadherence contributes to more than 125,000 deaths each
year in the U.S., costing the health care system over $177B annually. The
Joint Commission (JC) has found that prescribing and medication
administration errors typically occur when a patient is admitted to,
transferred within, or discharged from a health care facility.2
Moreover,
errors originating within the hospital can follow patients when they are
discharged, prolonging the harmful impact to the patient.
The medical device industry continues to churn out new, innovative
medication adherence solutions that range from very basic manual and
battery-operated devices to high tech systems that can handle more
complex patient care needs. A scan of the industry found 21 different
medication adherence technologies that can be used to store, organize,
and dispense medications, including some that can be programmed to
deliver medication reminders via phone, text, and email.
Our recommendation is that interested groups consider pilot studies to
test and measure outcomes from different medication adherence
technologies. This will help determine whether they add additional
benefits above and beyond the medication lists provided to patients at
discharge from the hospital.
1
See Appendix B: Medicine Safety – A Toolkit for Families.
2
http://www.jointcommission.org/sentinelevents/sentineleventalert/sea_35.htm.

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The Challenge
Medication errors harm an estimated 1.5M people and kill several
thousand each year in the U.S., costing the nation more than $3.5B
annually.4
According to the Joint Commission, accurate and complete
medication reconciliation can prevent prescribing and administration
errors. Techniques like medication reconciliation helps prevent omissions,
duplications, dosing errors, or drug interactions, and should be done at
every transition of care, when new medications are ordered, or when
existing orders are rewritten.5
However, the most problematic cause of
medication error is patient behavior, something not within the direct
control of the health care provider.
Patient Noncompliance
Fifty percent of patients are noncompliant with their medications.6
In a
meta-analysis looking at patient adherence to medical treatment,
researchers found a 76% discrepancy rate between the medicines
patients were prescribed, and those they actually took. Of those
discrepancies, 51% were due to patients taking unrecorded medicines;
29% were from patients not taking a prescribed medicine; and 29% were
from incorrect dosages.7
Additionally, 32M Americans take at least three
medications daily; 29% stop taking their medicine without their physician’s
consent; and 22% take less medication than is prescribed to them.8
Not
surprisingly, medication nonadherence has been called “America’s other
drug problem,” leading to needless disease succession and even
fatality.9,10
Furthermore, 10% of all hospital and 23% of all nursing home
admissions occur because patients fail to take their prescription
medications correctly.11
4
http://www.iom.edu/Object.File/Master/4/117/ToErr-8pager.pdf.
5
http://www.jointcommission.org/sentinelevents/sentineleventalert/sea_35.htm.
6
National Council on Patient Information and Education(NCPIE).
7
Bedell, S., et. al. 2000. Discrepancies in the Use of Medications. Archives of
Internal Medicine (July 24, 2000) Vol. 160.
8
http://www.americanheart.org/presenter.jhtml?identifier=107.
9
DiMatteo, M.R., et al. 2002. Patient Adherence and Medical Treatment
Outcomes: A Meta-Analysis. Med Care (September 1, 2002) 40: 794-811.
10
Ernst, F.R., and A.J. Grizzle. 2001. Drug-Related Morbidity and Mortality:
Updating the Cost-of-Illness Model. J American Pharmaceutical Association
(March-April 2001).
11
http://www.americanheart.org/presenter.jhtml?identifier=785.

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What can we do to improve medication adherence? Vendors of
technology-based medication adherence solutions claim their solutions
can help address the noncompliance problem in the home, where there is
no nurse or pharmacist to reconcile medications. Some studies have
confirmed this, showing that such solutions may have a place in a multi-
pronged approach.12,13,14
The Solutions
Medication adherence vendors offer in-home devices and software
packages for medication self-management featuring storage, dispensing
and organizing units, and reminder systems using email, phone, and text
messaging. The devices range from low tech manual and battery-
operated products to high tech systems that can be integrated into a
health care organization’s electronic medical record (EMR).
How Do They Work?
There are many different technology approaches to medication
adherence. Which one is best? Medication adherence is a problem that
affects many different populations such as pediatric and adult patients.
Thus the technology must be tailored to the target patient population.
The table below lists 21 different products, their key features, photos, and
website URLs where available. They represent the spectrum of products
available today. Typical device categories are pill boxes, reminder
systems, and sensors that measure post-ingestion and physiologic drug
uptake. One of the most striking things about this assorted batch of med
adherence gadgets is the broad range of features they offer.
12
Schoenthaler, A. 2008. Patients’ Perceptions of Electronic Monitoring Devices
Affect Medication Adherence in Hypertensive African Americans. The Annals of
Pharmacotherapy (April 8, 2008) 42(5): 647-652.
http://www.theannals.com/cgi/content/abstract/42/5/647.
13
Walker, E.A., et al. 2007. Adherence to Preventive Medications: Predictors and
outcomes in the Diabetes Prevention Program. Diabetes Care (September 2006)
29(9): 1997-2002.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1762037.
14
Riekert, K.A., and C.S. Rand. 2004. Electronic Monitoring of Medication
Adherence: When is High-Tech Best? J Clinical Psychology in Medical Settings
(March 2002) 9(1): 25-34.
http://www.springerlink.com/content/w76f76595kun74h6/.

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TABLE 1. Medication Adherence Solutions.
Product Name and Vendor
Product Availability
Product Features Product View
1. CADEX Medication
Reminder Watch (12-Alarm
Wristwatch) by ePill
Commercially Available
Medication reminder system with 12 daily alarm capacity,
alpha reminder messaging, and beeping sound with
medical snooze.
2. CareCalls by Freedom
Telecare
Commercially Available
Secure web-based application with 24/7 access to live
care call service plus the ability to automatically check on
clients, send reminders, and capture caregiver visit
results.
3. Compliance for Life
TM
by
iReminder
Commercially Available
Secure web-based customizable audio/voice reminder
system, including phone, email, and textmessaging.
4. CompuMed Medication
Dispenser by ePill
Commercially Available
Secure tamper-proof automated medication box and
reminder system that organizes and dispenses pills.
5. DialogMeds™ by Medica-
Safe
Clinical Trials
Secure web-based medication reminder and pill bottle
system controls and tracks pill dispensing, provides
reports, and handles medication packaging and refills.
6. Didit™ by The Gentle
Reminder
TM
Commercially Available
Manual plastic device that can be attached to the pill bottle
to display day and dose reminders.
7. Dispense-a-Pill by
HealthOneMed
Clinical Trials
Access-controlled automated medication box with
reminder system and dispenser.
8. EMMA
TM
System by
InRange Systems®
Commercially Available
Web-based medication management system that
documents drug compliance and enables the caregiver to
remotely manage medications.
http://seniorjournal.com/NEWS/Health/2007/7-06-21-
EMMA.htm.
9. Ingestible Medicine Pills by
Proteus Biomedical®
Clinical Trials
Raisin™ microchip-enabled ingestible pills to track
medication adherence.
http://www.thestandard.com/news/2009/01/16/briefly-
proteus-biomedicals-creates-ingestible-technology.
10. Implantable Electronics by
Proteus Biomedical®
Clinical Trials
ChipSkin™ technology protects implanted electronic
devices used to track physiologic parameters or deliver
medications from deteriorating.

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TABLE 1. Medication Adherence Solutions(continued).
11. Med-eMonitor by InforMedix
Clinical Trials
Automated medication box, reminder system, and
dispenser with detachable portable pill box.
http://boston.bizjournals.com/washington/stories/2008/03/
03/story9.html
12. Medication On Demand
(MOD)® by Avancen
Commercially Available
Automated bedside medication-on-demand system with
RFID wristband for patient identification.
13. MedSignals by MedSignals
Corp.
Commercially Available
Automated medication box, reminder system, and
dispenser with four separate web- or device-
programmable drug compartments.
14. Medtime XL by ePill
Commercially Available
Automated medication box and reminder system that
organizes and dispenses pills.
15. Monitored Automatic Pill
Dispenser MD2 by ePill
Commercially Available
Automatic medication box and dispenser with a phone
reminder system.
16. OnTimeRx® by AmeliaPlex
Commercially Available
Two-way mobile application featuring email, text
messages, phone, and pager reminders for daily pill
doses, doctor appointments, prescription refills, etc.
17. Pill Phone by Vocel
Commercially Available
The Pill Phone is a mobile handset application that sends
permission-based personalized reminders to patients to
take their medications or refill their prescriptions.
18. SMART by SIMpill
Commercially Available
Secure web-based medication adherence monitoring
system that detects nonadherence and sends alerts.
19. Seven-Day Organizer and
Reminder by ePill
Commercially Available
Automated 7-day pill organizer, medication box, reminder
system, and dispenser.
20. Timex Daily Medication
Manager® by MEDport
Commercially Available
Battery-operated pill box with audio, beeping, and visual
reminders.
21. The Talking Rx
TM
by
Dynamic Living
Commercially Available
Battery-operated pill bottle with integrated audio recording
device that can be programmed to verbalize the drug
information and prescription.

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The Larger Picture
Medication adherence is a complex problem with many contributing
factors. Beyond devices, there are other complementary approaches
depending on which aspect of the problem one is addressing.15
Contributing Factors:
1. Socioeconomic factors include limited English language
proficiency, low health care literacy, lack of family or social
support, and high medication cost.
2. Provider-patient and health care system factors include poor
provider communication skills, inability of the system to educate
patients and provide follow-up, patient information materials
written at too high a literacy level, and lack of continuity of care.
3. Cognitive factors include patient misperception of illness
severity, rejection of diagnosis or treatment, lack of motivation for
treatment, and functional limitations due to other conditions (e.g.,
mental retardation, psychotic disorders, depression, and chronic
conditions).
4. Therapy-related factors include complexity of medication
regimen, frequent changes in medication regimen, medications
with social stigma, and unpleasant side effects.
5. Other patient factors include physical and psychological issues,
such as visual and hearing impairment, self-perceived risk or
susceptibility to disease, general motivation, psychosocial stress,
anxiety, and alcohol or substance abuse.
Patient-related factors are just one determinant of adherence behavior.
Adherence is a complex behavioral process strongly influenced by the
environments in which people live and the characteristics of their health
care providers. Whether people take medications as directed depends on
knowledge and beliefs about their illness, motivation to manage it,
confidence in their ability to engage in illness-management behaviors,
and expectations regarding the outcome of treatment and the
consequences of poor adherence (World Health Organization, 2003).
15
http://www.who.int/medicinedocs/en/d/Js4883e/7.2.2.html.

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Alternative Solutions
Of the many interventions used to improve medication adherence, the
following were most often cited in the literature:
 Education to increase patient knowledge
 Using adherence aids such as medication refill reminders
 Prescribing fewer drugs or fewer doses
Simplifying a medication dosage regimen alone, however, is unlikely to
have an effect on a person who, for instance, does not believe that
medications will improve their health condition. Rather, getting to the root
cause of the nonadherence is the key to a successful intervention.
According to medication adherence experts, the ideal time to initiate
adherence interventions is when therapy first begins.
The Industry
Many different groups make up the medication adherence ecosystem and
industry16,17,18
– from individuals and their families and social networks to
big business, including pharmaceutical companies, health care
organizations, health care and patient safety consumer interest groups,
policy and lawmakers, technology companies, politicians and lobbyists,
and health care regulators and licensing and accrediting agencies. No
estimate of market size has been published, but if the $177B cost of
nonadherence is any indicator, the market is sizable.
President Obama signed a government stimulus package that allocates
$19B for health information technology (HIT), comparative effectiveness
research (CER), and medical research.19
Although the details are not
clear, there is hope throughout the country that at the very least, dollars
will be directed towards remote and home-based telehealth20
and
telemedicine21
solutions that may help improve medication adherence.
16
http://www.who.int/medicinedocs/en/d/Js4883e/6.1.3.html.
17
http://www.jointcommission.org/sentinelevents/sentineleventalert/sea_35.htm.
18
http://www.google.com/search?hl=en&q=medication+adherence+industry&start=
10&sa=N.
19
http://www.hrsonline.org/Policy/LegislationTakeAction/stimulus_signed_feb09.cf
m.
20
Delivery of health care services at a distance via communications technology.
21
The practice of medicine at a distance; in particular,teleconsultation.

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The Companies
The device companies in this report range from new startups
focused on a single product and solution, like Gentle
Reminder’s Didit, to research organizations creating disruptive
preclinical-stage products, like Proteus Biomedical’s Ingestible
Pill and Implantable Electronics. In a changing U.S. economy,
many technology giants like Intel, Google, and Microsoft are
also looking for new opportunities in health care. It would not
be surprising to see Microsoft and Google, who have already
created online personal health portals, enter the medication
adherence market.
Key Issues
There are several issues medication adherence devices raise for
healthcare organizations.
1. Technical integration. In some cases, vendors will need to
integrate with an organization’s infrastructure and connect
with legacy systems.
2. Cost. Medication adherence products are not currently
covered as a health plan benefit. Sorting out who should
bear the cost for these adherence aids will be an important
decision that must factor in longer term benefits such as
reduced hospital utilization and chronic care costs.
3. Security and HIPAA. Some of the technologies use third-
party vendors to host patient clinical data. Although all data
is stored in an encrypted format and transmitted between all
parties using a VPN and standard encryption, external
hosting does raise HIPAA and security management issues.
Additional transport layer security is required on SSL/TLS to
provide end-to-end security.
4. Patient acceptance and capability to use these
systems. Inherent to medication adherence is individual
cooperation. Current research has linked treatment
resistance to poor acceptance of enabling technologies. In
fact, nonadherence at the start of one study was the
strongest predictor of nonadherence two years later. Other
studies found high acceptance and capacity to use enabling
technologies by patients regardless of age, previous
computer experience, or socioeconomic background. Key
success elements included frequent delivery of educational
content and sessions with providers for self- testing and
feedback.

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5. Outcomes measurement. While patient acceptance of and
capability to use medication adherence technologies are key
outcome metrics to monitor, improvement in operational
efficiency and quality of care are equally as important.
Additionally, baseline metrics on disease- specific quality of
life, including general satisfaction, self-efficacy, and specific
satisfaction with treatment processes should be obtained
and compared regularly.
Recommendations
Medication adherence is a complex problem with many causative factors,
and a host of possible solutions depending on which piece of the puzzle
one is tackling. We recommend a holistic approach – a personalized
medication adherence strategy31
– that focuses on the case-specific
barriers to adherence. Such an approach is more likely to be successful
because it leverages educational and behavioral interventions, incentives,
and technology only where they are suitable to the case at hand.
The strategy should be developed in concert with the patient and applied
consistently by all the patient’s caregivers and providers. There should be
ongoing measurement of adherence as well as comparative effectiveness
of interventions, thus metrics need to be built into the strategy. How to
best deliver those metrics is a question every medication adherence pilot
team should address so that the organization can start to build a body of
expertise and experience.
One area where medication adherence strategies will play an important
role is telehealth. With telehealth programs currently underway in many
settings, I recommend that telehealth investigators measure the
outcomes of medication adherence interventions as an essential part of
study protocol.
31
Haynes, R.B., et al. 2009. Interventions for enhancing medication adherence
(Review). The Cochrane Library (2009) Issue 1. Hoboken, NJ: John Wiley &
Sons Ltd.
http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD000011/pdf_fs.ht
ml. Almost all of the interventions that were effective in the long term were
complex, including combinations of information, reminders, self-monitoring,
reinforcement, counseling, family therapy, psychological therapy, crisis
intervention, manual telephone follow-up, and supportive care.

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References
Agency References
Agency for Healthcare Research and Quality (AHRQ). 301.427.1364.
Website: www.ahrq.gov.
American Association of Poison Control Centers (AAPCC). 800.222.1222.
Website: www.aapcc.org.
American Society of Health-System Pharmacists. Website:
www.safemedication.com. Email: Safemedication@ashp.org.
Centers for Disease Control and Prevention (CDC). 800.311.3435.
Website: www.cdc.gov.
National Center for Complementary and Alternative Medicine (NCCAM).
888.644.6226. Website: www.nccam.nih.gov/timetotalk.
U.S. Food and Drug Administration (FDA). 888.463.6332. Website:
www.fda.gov.
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