Adherence: A review of Education, Research, Practice, and Policy in the United States

Abstract

Objective:
To describe the education, research, practice, and policy related to pharmacist interventions to improve medication adherence in community settings in the United States.

Methods:
Authors used MEDLINE and International Pharmaceutical Abstracts (since 1990) to identify community and ambulatory pharmacy intervention studies which aimed to improve medication adherence. The authors also searched the primary literature using Ovid to identify studies related to the pharmacy teaching of medication adherence. The bibliographies of relevant studies were reviewed in order to identify additional literature. We searched the tables of content of three US pharmacy education journals and reviewed the American Association of Colleges of Pharmacy website for materials on teaching adherence principles. Policies related to medication adherence were identified based on what was commonly known to the authors from professional experience, attendance at professional meetings, and pharmacy journals.

Results:
RESEARCH AND PRACTICE: 29 studies were identified: 18 randomized controlled trials; 3 prospective cohort studies; 2 retrospective cohort studies; 5 case-controlled studies; and one other study. There was considerable variability in types of interventions and use of adherence measures. Many of the interventions were completed by pharmacists with advanced clinical backgrounds and not typical of pharmacists in community settings. The positive intervention effects had either decreased or not been sustained after interventions were removed. Although not formally assessed, in general, the average community pharmacy did not routinely assess and/or intervene on medication adherence.

Education:
National pharmacy education groups support the need for pharmacists to learn and use adherence-related skills. Educational efforts involving adherence have focused on students' awareness of adherence barriers and communication skills needed to engage patients in behavioral change.

Policy:
Several changes in pharmacy practice and national legislation have provided pharmacists opportunities to intervene and monitor medication adherence. Some of these changes have involved the use of technologies and provision of specialized services to improve adherence.

Conclusions:
Researchers and practitioners need to evaluate feasible and sustainable models for pharmacists in community settings to consistently and efficiently help patients better use their medications and improve their health outcomes.

Full text

Rickles NM, Brown TA, McGivney MS, Snyder ME, White KA. Adherence: a review of education, research, practice,
and policy in the United States. Pharmacy Practice (Granada) 2010 Jan-Mar;8(1):1-17.
www.pharmacypractice.org (ISSN: 1886-3655) 1
ABSTRACT*
Objective: To describe the education, research,
practice, and policy related to pharmacist
interventions to improve medication adherence in
community settings in the United States.
Methods: Authors used MEDLINE and International
Pharmaceutical Abstracts (since 1990) to identify
community and ambulatory pharmacy intervention
studies which aimed to improve medication
adherence. The authors also searched the primary
literature using Ovid to identify studies related to the
pharmacy teaching of medication adherence. The
bibliographies of relevant studies were reviewed in
order to identify additional literature. We searched
the tables of content of three US pharmacy
education journals and reviewed the American
Association of Colleges of Pharmacy website for
materials on teaching adherence principles. Policies
related to medication adherence were identified
based on what was commonly known to the authors
from professional experience, attendance at
professional meetings, and pharmacy journals.
Results: Research and Practice: 29 studies were
identified: 18 randomized controlled trials; 3
prospective cohort studies; 2 retrospective cohort
studies; 5 case-controlled studies; and one other
study. There was considerable variability in types of
interventions and use of adherence measures.
Many of the interventions were completed by
*Nathaniel M. RICKLES. Pharm.D., Ph.D., BCPP.
Assistant Professor of Pharmacy Practice &
Administration. Department of Pharmacy Practice,
Northeastern University School of Pharmacy. Boston, MA
(United States).
Todd A. BROWN. MHP, RPh. Vice Chair, Department of
Pharmacy Practice. Northeastern University School of
Pharmacy. Boston, MA (United States).
Melissa S. MCGIVNEY. PharmD, FCCP. Associate
Professor of Pharmacy & Therapeutics. Director,
Community Practice Residency Program, University of
Pittsburgh School of Pharmacy. Pittsburgh, PA (United
States).
Margie E. SNYDER, PharmD, MPH. Assistant Professor
of Pharmacy Practice, School of Pharmacy &
Pharmaceutical Sciences, Purdue University. Indianapolis,
IN (United States).
Kelsey A. WHITE, Pharm.D. Candidate. Northeastern
University School of Pharmacy. Boston, MA (United
States).
Series editors:
Marie P. SCHNEIDER. PhD. Researcher and lecturer in
Pharmacy Practice. Community Pharmacy, Dpt of
ambulatory care and community medicine, University
Hospital, Lausanne (Switzerland).
Parisa ASLANI. PhD. Senior Lecturer in Pharmacy
Practice. Faculty of Pharmacy, University of Sydney
(Australia).
pharmacists with advanced clinical backgrounds
and not typical of pharmacists in community
settings. The positive intervention effects had either
decreased or not been sustained after interventions
were removed. Although not formally assessed, in
general, the average community pharmacy did not
routinely assess and/or intervene on medication
adherence.
Education: National pharmacy education groups
support the need for pharmacists to learn and use
adherence-related skills. Educational efforts
involving adherence have focused on students’
awareness of adherence barriers and
communication skills needed to engage patients in
behavioral change.
Policy: Several changes in pharmacy practice and
national legislation have provided pharmacists
opportunities to intervene and monitor medication
adherence. Some of these changes have involved
the use of technologies and provision of specialized
services to improve adherence.
Conclusions: Researchers and practitioners need to
evaluate feasible and sustainable models for
pharmacists in community settings to consistently
and efficiently help patients better use their
medications and improve their health outcomes.
Keywords: Medication Adherence. Pharmacists.
Education, Pharmacy. United States.
CUMPLIMIENTO: REVISIÓN DE LA
EDUCACIÓN, INVESTIGACIÓN, PRÁCTICA
Y POLÍTICA EN ESTADOS UNIDOS
RESUMEN
Objetivo: Describir la educación, investigación,
practica y política relacionadas con las
intervenciones farmacéuticas para mejorar el
cumplimiento de la medicación en establecimientos
comunitarios en Estados Unidos.
Métodos: Los autores utilizaron Medline e
International Pharmaceutical Abstracts (desde
1990) para identificar los estudios de intervención
de farmacia comunitaria y ambulatoria que trataban
de mejorar el cumplimiento de la medicación. Los
autores también buscaron en literatura primaria
usando Ovid para identificar estudios relativos a la
enseñanza de farmacia sobre cumplimiento de la
medicación. Se revisaron las bibliografías de los
estudios relevantes para identificar literatura
adicional. Buscamos en los sumarios de tres
revistas de educación de farmacia de Estados
Unidos y se revisó la web de la Asociación
Americana de Facultades de Farmacia a la busca de
materiales sobre principios de educación sobre
International Series: Adherence
Adherence: a review of education, research,
practice, and policy in the United States
Nathaniel M. RICKLES, Todd A. BROWN, Melissa S. MCGIVNEY, Margie E. SNYDER , Kelsey A. WHITE.
Received (first version): 18-Jan-2010 Accepted: 1-Mar-2010

Rickles NM, Brown TA, McGivney MS, Snyder ME, White KA. Adherence: a review of education, research, practice,
and policy in the United States. Pharmacy Practice (Granada) 2010 Jan-Mar;8(1):1-17.
www.pharmacypractice.org (ISSN: 1886-3655) 2
cumplimiento. Las políticas relacionadas con
cumplimiento de medicación se identificaron
mediante lo que era conocido por los autores desde
su experiencia profesional, asistencia a congresos y
revistas farmacéuticas.
Resultados: Investigación y práctica: se
identificaron 29 estudios: 18 ensayos controlados
aleatorizados; 3 estudios de cohorte prospectivos; 2
estudios de cohorte retrospectivos; 5 estudios de
caso control; y otro estudio. Hubo una considerable
variabilidad en los tipos de intervenciones y en el
uso de medidas del cumplimiento. Muchas de las
intervenciones eran realizadas por farmacéuticos
con formación clínica avanzada y no por típicos
farmacéuticos comunitarios. Los efectos positivos
de las intervenciones disminuyeron o no se
mantuvieron después de que las intervenciones
desaparecieron. Aunque no se evaluó formalmente,
en general, las farmacias comunitarias normales no
evaluaban rutinariamente y/o intervenían en el
cumplimiento de la medicación.
Educación: Los grupos nacionales de educación de
farmacia apoyan la necesidad de que los
farmacéuticos aprendan y usen habilidades
relacionadas con el cumplimiento. Los esfuerzos
educativos relacionados con el cumplimiento se han
centrado en el conocimiento de los estudiantes de
las barreras al cumplimiento y en las habilidades de
comunicación necesarias para envolver a los
pacientes en un cambio actitudinal.
Política: Varios cambios en el ejercicio de la
farmacia y en la legislación nacional han
proporcionado a los farmacéuticos la oportunidad
de intervenir y monitorizar el cumplimiento de la
medicación. Algunos de estos cambios incluyeron
el uso de tecnologías y la provisión de servicios
especializados para mejorar el cumplimiento.
Conclusiones: Los investigadores y facultativos
necesitan evaluar modelos factibles y sostenibles
para los farmacéuticos en la comunidad para ayudar
consistente y eficientemente a pacientes en su
mejor uso de las medicaciones y mejorar sus
resultados en salud.
Palabras clave: Adherencia a la medicación.
Farmacéuticos. Educación farmacéutica. Estados
Unidos.
INTRODUCTION
Medication adherence or the older term, medication
compliance, is defined as the extent to which a
person’s medication use behavior coincides with
medical or health advice; and persistence as the
duration of time from initiation to discontinuation of
therapy.1 Medication non-adherence and the lack of
persistence is a severe and pervasive problem
involving many not yet fully understood aspects of
individual behavior and gaps in service delivery, and
which often results in negative patient outcomes
such as poor clinical outcomes and increased
hospitalizations.2-6 Such negative outcomes are
associated with recent United States (US)
healthcare costs estimated to be USD290 billion a
year.7 Research has shown non-adherence to many
medications to range from 40 to 50%.8
After several decades of research, we have learned
that medication non-adherence is due to many
factors including lack of adequate knowledge about
medication and treatment goals, beliefs about the
medication, complex regimens that are difficult to
manage, side effects, and costs associated with
medications.9-11 There have been several studies
over the years showing how different interventions
can improve treatment adherence.12 In general,
research shows that patient-centered, multi-modal
educational and behavioral interventions are more
effective than one approach.12 Intervention
approaches have included the use of various
reminder systems, simplification of drug regimens,
medication counseling, and collaborative team
approaches, involving multiple healthcare providers,
as well as follow-up and monitoring.12,13 A relatively
recent systematic review indicated that simple
interventions (such as a medication calendar or
pillbox) improved adherence and other outcomes for
short-term treatments.13 Such effects, however,
were inconsistent with less than half of the studies
showing benefits. Efforts to improve adherence to
chronic medications are often complex and
ineffective making it hard to interpret the full benefits
of treatment.
In the United States, there has been a growing
literature showing that pharmacists in a variety of
practice settings and across different disease states
have an important role to play in medication therapy
management (MTM) activities including optimization
of medication adherence. Many of the studies in the
last two decades have contextualized MTM
activities as a part of the pharmacist’s direct
responsibilities for patient outcomes commonly
known as “pharmaceutical care”.14 The
pharmaceutical care movement has focused on the
pharmacists’ responsibility to care for patients’
medication-related needs including adherence. The
American Association of Colleges of Pharmacy
(AACP) Commission to Implement Change in
Pharmaceutical Education has embraced
“render[ing] pharmaceutical care” as pharmacy
practice’s mission.15 These ideals are further
reflected by the Joint Commission of Pharmacy
Practitioners (JCPP) (representing 11 US pharmacy
organizations). The JCPP vision states that
“pharmacists will be the health care professionals
responsible for providing patient care that ensures
optimal medication therapy outcomes” and that
“pharmacy education will prepare pharmacists” to
provide this care.16
In conjunction with the pharmaceutical care
movement of the 1990s, US schools and colleges of
pharmacy expanded their curriculums and require
all pharmacy graduates to complete a six-year
clinical doctoral degree (PharmD degree). This
curricular expansion enabled students to learn more
clinical skills and gain additional patient care
experiences. Such additional skills should position
all current pharmacy graduates, regardless of
practice setting, to help improve patient medication
use.

Rickles NM, Brown TA, McGivney MS, Snyder ME, White KA. Adherence: a review of education, research, practice,
and policy in the United States. Pharmacy Practice (Granada) 2010 Jan-Mar;8(1):1-17.
www.pharmacypractice.org (ISSN: 1886-3655) 3
Before the all-PharmD graduation requirement,
pharmacists with advanced clinical knowledge
would often use their additional clinical skills
working in institutional settings. It was generally
viewed that pharmacists practicing in community
settings such as community pharmacies did not
have the expertise or time to follow-up and provide
additional clinical services. However, the influx of
doctor of pharmacy graduates into community
pharmacies along with the proliferation of
community pharmacy residency programs has
brought about interest and participation in the
provision of additional clinical services by
community pharmacists. Although there is a
growing database of US studies evaluating the role
of pharmacists working in community pharmacies
and other ambulatory settings to improve
medication adherence, the present review is
believed to be the first manuscript compiling and
analyzing these recent studies.
Compared to other countries, the US literature on
community and ambulatory pharmacist interventions
to improve adherence is fairly large. Many would,
however, view the literature as relatively small and
agree there needs to be considerably more
research done in the area. This literature also forms
the foundation for both current educational efforts in
the US Schools and Colleges of Pharmacy related
to teaching medication adherence, and policies and
practices being advanced by various local, state,
and national organizations. The present manuscript
will explore all these aspects by first reviewing the
ambulatory and community pharmacy adherence
studies, then shifting to a review of current
educational efforts underway in US Schools and
Colleges of Pharmacy, and ending with current
policies and practices related to the community
pharmacist’s role in medication adherence.
Pharmacy Interventions in Ambulatory and
Community Settings
Methodological Approach
The databases MEDLINE and International
Pharmaceutical Abstracts since 1990 were
searched using the following key MeSH terms
“pharmacist* or community pharmacist*” and
“adherence or compliance” and “United States”. The
asterisk indicates that multiple variations of the term
were searched (i.e., pharmacist, pharmacies,
pharmacists). Studies with an intervention delivered
by pharmacists practicing in an ambulatory or
community pharmacy setting and that measured
medication adherence were included. All study
designs were included. A hand search of the
bibliographies of the included studies was also
conducted to identify research that was not found in
the database search.
If a study reported a significant adherence finding, a
statement describing the finding as well as the
extent of significance (such as if the p value is ≤ to
0.05, 0.01, or .001 or the presence of a confidence
interval) was included. If the study reported no
statistically significant difference this was stated
without the statistical measure.
Results
The literature search resulted in 29 studies17-48
including 18 randomized controlled trials, 3
prospective cohort studies, 2 retrospective cohort
studies, 5 case-controlled studies, and one other
study. Annex 1 lists the studies that were included
as well as the setting, intervention, adherence
measures, and results. All of the studies included in
this review involved interventions intended to
improve medication adherence. Some studies
explored the improvement of adherence as the
primary endpoint and other studies viewed
improved adherence as an intermediate outcome
leading to improved clinical outcomes.
In 38% (11/29) of the studies a change in
medication adherence was not seen.17-
20,26,27,29,31,35,43,47 In 24% (7/29) of the studies, an
inadequate sample size to detect differences in
adherence was identified as a
limitation.19,24,25,28,29,35,43 The use of self-reported
medication adherence was also problematic as
baseline medication adherence was frequently
higher than expected (patients often overestimate
their adherence).22,26,28,29,35,43 Higher baseline
adherence reduces the potential for change in
adherence in patients receiving the intervention.
The interventions used in the studies varied greatly
from very specific packaging to multi-modal
educational and behavioral interventions. Despite
these issues many studies did demonstrate a
change in adherence. Forty-four percent (8/18) of
the randomized controlled studies reported at least
one statistically significant adherence result. These
studies demonstrated that ambulatory and
community pharmacists can provide services that
increase medication adherence. Additional research
on the specific activities that produce these results
would allow them to be reproduced.
In some studies, a change in adherence was
observed soon after the start of the intervention. In
others, it took some time for the intervention to
influence adherence. It is not clear why this is the
case but we suspect that patients require time to
make cognitive and behavioral adjustments during
behavioral change. Three studies also
demonstrated that unless the intervention was
continued, the change in adherence decreased or
did not persist.33,34,36 Research is needed to identify
which patients are most likely to benefit from these
services and to determine the most cost-effective
method of providing these services.
In sixteen of the 29 studies (55%) the interventions
were delivered by clinical pharmacists practicing in
ambulatory settings and employed by the
institutions where the care was being
provided.17,19,20-24,26,30.32-34,36,41-43,47 Greater
involvement by community pharmacists who work in
retail settings is needed to provide these services to
larger patient populations. Community pharmacists
are in an ideal position to provide long-term
adherence services as they have access to
medication refill histories and have routine contact
with patients. It is important to recognize that there
were no known studies assessing the extent to
which pharmacists in community settings routinely

Rickles NM, Brown TA, McGivney MS, Snyder ME, White KA. Adherence: a review of education, research, practice,
and policy in the United States. Pharmacy Practice (Granada) 2010 Jan-Mar;8(1):1-17.
www.pharmacypractice.org (ISSN: 1886-3655) 4
assess and intervene on medication adherence. It is
generally believed that the average pharmacist in
the community setting does not regularly assess
and intervene on medication adherence.
Review of Educational Efforts in US Schools
and Colleges of Pharmacy
Overview
The promotion of medication adherence is one
component of pharmaceutical care practice and is
considered one of four basic needs that patients
have related to their medications.49 The outcomes
of AACP’s Center for the Advancement of
Pharmaceutical Education (CAPE) support the need
for practitioners skilled in medication adherence
principles. Both the “pharmacy practice” and “social
and administrative pharmacy” documents
supplementing the CAPE outcomes specifically
indicate promoting adherence under the outcome of
“pharmaceutical care”.50-52 However, US schools
and colleges of pharmacy have varied greatly in
providing education related to medication
adherence. A 2005 survey of communication skills
assessed by 50 US schools and colleges of
pharmacy found that only 22% of institutions
assessed students on any adherence-related
skills.53 The current review aims to identify specific
educational practices used by US schools and
colleges of pharmacy to develop adherence
promotion skills among students. The examples
provided in this section are not necessarily from the
same schools and colleges of pharmacy identified in
the 2005 survey that assessed students on
adherence-related skills. Further, these examples
represent those that have been published as
examples of curricular innovations to teach students
about medication adherence.
Methodological Approach
After a brief Internet search, we formally searched
primary literature using Ovid, combining the MeSH
terms “Education, Pharmacy” and “Medication
Adherence.” We also searched using the
combinations of “Education, Medical” and
“Medication Adherence” along with “Education,
Medical” and “Education, Pharmacy” combined with
“Patient Compliance.” We searched motivational
interviewing as it is considered an important
technique for clinicians to use to engage patients in
changing their medication adherence behavior.
Further, we reviewed the bibliographies of relevant
articles in order to identify additional literature. We
also searched the tables of content of three current
US journals focusing on pharmacy education:
American Journal of Pharmaceutical Education, the
International Journal of Pharmacy Education and
Practice, and Currents in Pharmacy Teaching and
Learning. These journals were searched for articles
related to “adherence”, “compliance” and
“motivational interviewing.” Finally, we reviewed the
AACP website for any tools or recommendations on
teaching adherence principles.
Results
In the US, many of the efforts in pharmacy
education to teach adherence principles have
focused on exposing students to the numerous
difficulties associated with adhering to a medication
regimen. The teaching strategies often involve the
student pharmacists consuming placebo
medications (e.g., small candies) for a short period
of time in order to gain a sense of what it is like to
be a patient. For example, at Idaho State University,
first and third year professional students are paired
for four weeks.54 The first year students play the
role of patient and are “prescribed” a complex
medication regimen for which the third year student
provides counseling and assessment. Through this
experience, specific barriers to medication use are
identified and students reflect on their experience.
Similarly, Singla and colleagues at Midwestern
University (Glendale, Arizona) described an
educational program that brought pharmacy and
osteopathic medical students together to learn
about medication adherence.55 In this experience,
medical students role-played physicians with a
needle-stick requiring HIV prophylaxis therapy. The
pharmacy students then provided patient counseling
and an assessment of adherence. This activity was
four weeks in duration and many barriers to
adherence were discussed. Also focusing on
regimens for HIV, faculty at West Virginia University
designed a program to expose pharmacy students
to the difficulties associated with adhering to
antiretroviral therapies.56 Students took placebos for
one week, similar to the other studies described
above, and recorded their adherence on a log
sheet. The students reported many common
barriers to medication adherence. Finally, Divine
and colleagues reported on an adherence
simulation program at the University of Kentucky
that involved students using multiple “medications”
for 10 days in order to better understand the
experiences of geriatric patients.57
There appear to be limited published examples of
programs in pharmacy education designed to
specifically develop student communication skills
that promote adherence. One example is from
Auburn University, a pharmacy school with experts
in motivational interviewing. As described by
Villaume and colleagues, “treatment nonadherence
results from patient ambivalence and resistance”.58
At Auburn, educators have created the “Auburn
University Virtual Patient.” This program allows
students to consider each part of a patient-
pharmacist interaction and reflect on how the
success of the conversation is impacted by what is
said by the pharmacist. During the prototype stage
of the Virtual Patient program, students created
“scripts” for the Virtual Patient, including Virtual
Patient responses and how the student would
respond using both motivational interviewing
techniques and a traditional “biomedical” approach.
These exercises help the students understand how
effective/ineffective conversations unfold and how
such conversations impact patient outcomes.
Another recent paper described the use of
standardized patients or actors in a communication

Rickles NM, Brown TA, McGivney MS, Snyder ME, White KA. Adherence: a review of education, research, practice,
and policy in the United States. Pharmacy Practice (Granada) 2010 Jan-Mar;8(1):1-17.
www.pharmacypractice.org (ISSN: 1886-3655) 5
skills course and lab as a way for students to
actively learn how to counsel patients who are non-
adherent to drug therapy.59 Students were given
medication profiles reflecting non-adherence to a
drug therapy. The students were expected to detect,
assess, and intervene on the medication non-
adherence. The standardized patients were given
scripts to indicate, when elicited from the student,
various issues they were having with the
medications. Students were given these same
scenarios at the beginning and end of the course.
Using a structured communication skills
assessment form, students’ communication skills
were assessed during both times. The educators
used the changes in the evaluation form at the
beginning and end of the course as a way to assess
student learning on how to effectively intervene
using communication skills on patient non-
adherence.
Although a review of the literature revealed a small
number of published examples describing teaching
approaches to engaging more students in
medication adherence assessment and intervention
techniques, further educational research is
warranted. It is reasoned that the more students
practice such approaches before they graduate, the
more likely they will engage in such activities when
practicing as pharmacists.
Current Policies and Practices Related To
Pharmacy Medication Adherence Activities
Methodological Approach
Policies related to medication adherence were
identified based on what was commonly known to
the authors from professional experience,
attendance at professional meetings, and pharmacy
journals. The authors did not employ any specific
electronic literature database(s) or other formal
mechanism to ascertain current policies related to
medication adherence.
Results
There have been several policies and practices over
the last three decades that support the role of the
US pharmacist in community settings to engage in
adherence interventions. For over two decades,
most community pharmacies have maintained
computerized prescription profiles that allow them to
identify late refills. These computerized profiles are
only appropriate estimates of refill patterns when
the patient only uses the pharmacy or chain of
pharmacies (assuming the particular chain
pharmacies have linked computer systems). If the
patient goes to multiple pharmacies, gaps in their
profiles may inaccurately reflect non-adherence.
Many of the computer software programs also have
capabilities to display electronic messages
indicating the patient is late in picking up refills.
Unfortunately, the busyness of most community
pharmacy practices makes it difficult for
pharmacists to consistently engage patients when
they see these messages pop up on their screens.
Large chain pharmacies have also recently
implemented tools and programs to improve
adherence. For example, several of the large
pharmacy chains have tools on their company
websites in which patients can sign up and have
reminders to take their medications sent
electronically to their cell phones, home/office
numbers, and e-mail addresses. Some of the chains
have telephone-based programs to call patients
when they are late in picking up their medications
and simply remind them to pick up their
medications. Nearly all community pharmacies sell
pillboxes that can help patients remember when to
take their medications. Select and perhaps more
progressive pharmacies collect fees for packaging a
patient’s monthly medications into boxes or blister
packs. Some pharmacies have attempted to
synchronize the prescription refills for patients. This
helps the pharmacy by making the workload more
predictable and ensures that the patient has needed
medications.60 There are also several companies
that have started up to help pharmacies identify
patients such as those non-adherent requiring
additional and personalized services. Mirixa61,
PurpleTeal62, Aprexis Health Solutions63, Outcomes
Pharmaceutical Health Care64, and Medication
Management Systems, Inc.65 are just a few
examples of new companies focused on helping
pharmacists provide adherence services.
In addition to pharmacy-driven initiatives to improve
adherence, there have been some efforts by federal
and state governments for community pharmacists
to improve adherence. At the federal level, the
passage of the US Medicare Modernization Act of
2003 and the Medicare Prescription Medication
Benefit (Part D) formally marked the initiation of
Medication Therapy Management (MTM) services
for patients enrolled in Medicare, a federal program
providing medical and prescription coverage for
older adults.66 The Centers for Medicare and
Medicaid Services describe MTM as a means to
ensure that “medications prescribed for targeted
beneficiaries are appropriately used to optimize
therapeutic outcomes and reduce the risk of
adverse events”.67 MTM has been further defined by
the profession as “a distinct service or group of
services that optimize therapeutic outcomes for
individual patients [that] are independent of, but can
occur in conjunction with, the provision of a drug
product”.68
The American Pharmacists’ Association and the
National Association of Chain Drug Stores
Foundation provide further guidance by defining the
“core elements” of an MTM service, including
medication therapy review, personal medication
record, medication action plan, intervention and/or
referral, and documentation and follow-up.69 While
the “core elements” serve as a basis for all MTM
services, the mechanisms to enroll patients and to
provide compensation to the pharmacist to care for
the patient differ based on the payer.
In 2009, an average of 13% of patients receiving
Medicare was provided MTM.69 Each individual
Medicare insurance plan has unique criteria for
MTM enrollment. Eighty-four percent of plans
required the beneficiary to be taking two to five
Medicare-covered medications and be treated for
two to three chronic diseases.70 The five most

Rickles NM, Brown TA, McGivney MS, Snyder ME, White KA. Adherence: a review of education, research, practice,
and policy in the United States. Pharmacy Practice (Granada) 2010 Jan-Mar;8(1):1-17.
www.pharmacypractice.org (ISSN: 1886-3655) 6
common chronic conditions were diabetes, heart
failure, hyperlipidemia, COPD and hypertension.70
Additionally, a further criteria for enrollment was that
the total medication costs, as paid by both patients
and insurers, was over USD4000 a year for
medications.
The most common mechanisms to provide care and
contact with the patient were: medication reviews,
phone outreach, face-to-face contact, refill
reminders, intervention letters, educational
newsletters, prescriber consults, drug interaction
screenings, case management and medication
profiles or lists.70 While patient adherence is not
currently a required outcome marker of Medicare, it
can be inferred from the types of patient contact that
it is a component of most of the Medicare-supported
MTM programs. The payments for the provision of
MTM is unique to each Medicare insurance plan
with the majority of plans using in-house staff.70,71
Examples of MTM programs and networks that
engage community-based pharmacists in the
provision of MTM to Medicare beneficiaries include:
Humana72, Mirixa61, and Outcomes Pharmaceutical
Health Care.64 The use of community-based
pharmacists is likely to increase during the 2010
calendar year because the new requirements for
MTM programs are that the services must be
delivered face-to-face.73
At the state level, some states for many years have
been reimbursing pharmacists for adherence
activities provided to patients receiving state
prescription coverage due to having a low income
and other eligibility requirements (called
Medicaid).74 More recently, individual state Medicaid
programs have also partnered with pharmacists to
provide MTM to their beneficiaries. Select states
that are known to have MTM programs which
engage community-based pharmacists include:
Iowa, Minnesota, North Carolina, Florida,
Mississippi, Montana, Ohio, Vermont, and
Wyoming.75 As with Medicare MTM programs,
adherence is not a required outcome measure in all
of these programs, but the programs do generally
identify patients with multiple medications and
multiple chronic conditions. There are a number of
additional states with programs starting and
advocacy for such programs underway. A common
theme between most of the programs is they were
established with a partnership of the state
pharmacists association, the schools or colleges of
pharmacy located within the state, and the state
Medicaid program.
Aside from these efforts, several foundations,
pharmaceutical companies, and federal agencies
(such as the National Institutes of Health) have
provided researchers grants to explore and evaluate
adherence interventions by community pharmacists.
The Pharmacy Quality Alliance (PQA), a non-profit
organization, has developed a collaborative
program focused on improving the quality of
medication use across multiple health settings.76
One of their many initiatives has been examining
through pilot research the use of adherence
measures as a benchmark for the quality of
community pharmacies. Such initiatives are
controversial as they assume that pharmacies
should be responsible for patient medication
adherence behaviors. Many community pharmacists
feel they can’t be responsible for a patient’s rational
decision to not take their medications as prescribed.
Others say that pharmacists should be responsible
for adherence outcomes if one supports the
philosophy of pharmaceutical care and pharmacists
being directly responsible for patient drug therapy
outcomes. One potential consequence of this work
is that adherence measures are created for each
pharmacy and publicly reported as an index for
each pharmacy’s quality of care. Clearly, more
research will need to be conducted before all can
accept adherence measures as a benchmark for
pharmacy quality.
CONCLUSIONS
The present review describes several trials showing
the impact of pharmacists in community settings on
patient adherence. While a majority of studies show
pharmacists having a significant impact on
medication adherence, there are several as well
showing the lack of an impact on adherence. In
some cases, the lack of impact may be due to
sample size and study design issues. It is not clear
how well researchers assessed the consistency to
which the interventions were carried out (program
fidelity) and may account for some of the decreased
impact. It is also not clear how many of the
interventions described are sustainable and being
actively maintained in practice.
The practice model used for many of the
interventions in the review involved face-to-face
visits via appointments. Due to heavy prescription
volumes associated with most US pharmacies, it
seems impractical to expect appointment-based
care to be the sole model of adherence
interventions. Telephone-based adherence
management was another model explored and
could better fit into current practice patterns as calls
could be made during slower times. This latter
approach is still fraught with problems as it is not
always clear when to consistently plan calls, and
patient availability often does not match pharmacist
availability. In these latter “in-house” (at the
pharmacy site) models of adherence intervention
and monitoring, it is also likely additional pharmacy
staff may need to be hired to offset the time given
for such adherence initiatives. Such additional costs
may not be feasible for many US pharmacies
struggling to maintain profits given heavy
competition and lean reimbursements from
insurance companies. Further, to survive financially,
community pharmacists need to be reimbursed for
their time (face-to-face or via telephone) in helping
patients manage their medications. Reimbursement
efforts at the federal and state level as described
previously are helpful and making it more possible
for community pharmacists to engage in these
activities without incurring financial hardships.
Similar efforts are also needed by private insurance
payers in compensating pharmacists for their
services.

Rickles NM, Brown TA, McGivney MS, Snyder ME, White KA. Adherence: a review of education, research, practice,
and policy in the United States. Pharmacy Practice (Granada) 2010 Jan-Mar;8(1):1-17.
www.pharmacypractice.org (ISSN: 1886-3655) 7
There needs to be more research to explore other
models for which pharmacists in community settings
can consistently and actively engage in adherence
interventions and monitoring. One model currently
being explored by the lead author of this review
involves pharmacists at an off-site location making
outbound calls to patients regarding ways to
improve adherence. The primary disadvantage of
the model is the difficulty for patients to establish a
relationship with a pharmacist they do not know
over the phone. However, the key advantage of the
model is that it avoids the point-of-service and
economic demands of prior models.
Future research should not only test these latter
models for feasibility and effectiveness but also
explore how pharmacists can approach adherence
interventions and monitoring at the population level.
For example, are there tools or algorithms that can
be developed that allow pharmacists to stratify
individuals based on degree of risk for non-
adherence and that the nature and extent of
interventions be based on patient’s degree of risk?
We need such tools to help pharmacists in
community settings efficiently deliver the right dose
of patient-centered interventions to those in need.
Therefore, research is needed to identify the
resources and models of practice best to provide
these services in a community pharmacy setting.
Additional educational research is warranted to
identify effective strategies for preparing
pharmacists to assist patients in medication
adherence. It is clear that by delivering efficient and
effective adherence interventions, US pharmacists
in community settings can have a significant and
cost-effective impact on improving the health of our
communities.
CONFLICT OF INTEREST
None declared.
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10
Annex 1.
Study Condition Methods Intervention Adherence Measure Adherence Outcomes
Randomized Controlled Trials
Hypertension
17. Carter BL et
al. (2008)
Hypertension  N=179
 Intervention clinics vs.
control clinics
 9 months
 5 clinics within 15 miles of
Iowa City, IA
 Clinical Pharmacists
Identified suboptimal
medication regimens,
recommended adherence
aids and negotiated strategy
with patient to improve
adherence
Medication adherence at 9 months
calculated from pill counts as the
percent of predicted doses
measured at each study visit

Significantly greater adherence at
baseline in control group (89%
vs. 71%, p<0.001)
 Only 4% of recommendations
involved adherence
 No difference in adherence at 9
months (92% in control group vs.
94% in intervention group)
18. Planas LG et
al. (2009)
Hypertension  N=52
 Pharmacist intervention vs.
Control
 49months
 5 community pharmacies in
Tulsa, OK
 Community Pharmacists
Provided medication therapy
management services
including education on
medications, identification
and resolution of drug
therapy problems,
adherence assessment and
personalized plans as
needed
Adherence measured from claims
history provided by the managed
care organization using a
medication acquisition method
Mean adherence during study period
(control vs. intervention 78.8% vs.
87.5%, p=ns
19. Mehos BM
et al. (2000)
Hypertension  N=36
 Control vs. Pharmacist
Intervention
 6 months
 Family medicine residency
training clinic in Denver, CO
 Clinical Pharmacists
Gave blood pressure
monitor and performed
monthly telephone calls to
evaluate blood pressure
response
Percent adherence calculated by
dividing the number of
tablets/capsules refilled by the
amount prescribed during the
study
Change in adherence not seen:
Control: 89% vs. Intervention: 82%
Elderly Patients
20. Hanlon JT et
al. (1996)
Elderly patients
with 5 or more
regularly scheduled
medications
 N=208
 Usual care vs. usual +
clinical pharmacist care
 1 year
 General Medicine Clinic in
Durham, NC
 Clinical Pharmacists
Encouraged patient
adherence using both
adherence-enhancing
strategies (reminder
packages/calendars) and
written patient education
materials
Self-reported: the proportion of
medications for which patients’
response agreed with the
directions for their use. This
approach was chosen based on a
study showing the self-reported
medication use and actual use
were comparable in elderly
patients.
Adherence: No statistically significant
change Intervention: 77.4% vs.
Control: 76.1%

11
21. Lee JK et al.
(2006)
Elderly patients
with at least 4
chronic
medications
 N=200
 Pharmacy Care (PC) vs.
Usual Care (UC) in 3
phases
 14 months
 Medical center in
Washington, DC
 Clinical Pharmacists
Individualized medication
education, medications
dispensed using an
adherence aid, and regular
follow-up for 6 months. Half
were randomly selected for
an additional 6 months of
intervention.
 Proportion of pills taken from
blister packs on months 4, 6,
8, 10, 12, and 14 measured
by pill counts
 Primary outcome: change in
medication adherence

Mean adherence (%):
Baseline: 61.2
8 month for PC group 96.9
(p<0.001)
14 month UC 69.1 vs. PC 95.5
(p<0.001)
 ≥80% adherent (%):
PC @ 14 months: 97.4
UC @ 14 months: 21.7 (p
<0.001)
HIV/AIDS
22. Rathbun, RC
et al. (2004)
HIV/AIDSa  N=33
 Adherence clinic (AC) vs.
standard care (SC)
 7 months
 HIV clinic in Oklahoma City,
OK
 Clinical Pharmacists
Educated about appropriate
administration of HAARTb,
food restrictions, adverse
event management
strategies, and monitored
patient progress after
therapy initiation with follow-
up as needed
Electronic monitoring device used
to measure:
 Medication consumption
(number of doses consumed
divided by number of
prescribed doses)
 Dose precision (percent of
doses taken at the prescribed
interval calculated by number
of doses taken within 1.5
hours of interval divided by
total number of prescribed
doses)
 Self-reported adherence
using a validated, 2-page
questionnaire to assess
adverse events, patient
perception of treatment, and
adherence during the
preceding week. Was
administered at weeks 4,16,
and 28.

Medication consumption AC vs.
SC:
Week 4: 86% vs. 73%
Week 16: 77% vs. 56%
Week 28: 74% vs. 51%
 Dose Precision (AC vs. SC):
Week 4: 69% vs. 42%, (p< 0.05)
Week 28: 53% vs. 31%, (p< 0.05)
 Self-reported adherence*: (AC
vs. SC) 94% vs. 89%
Depression
23.& 24. Finley
PR et al. (2002
& 2003)
Depression  N=125
 Collaborative care model
group vs. Control group
 6 months
 Medical Center in San
Rafael, CA
 Clinical Pharmacists
Titrated medication doses
with scheduled follow-up
appointments and telephone
calls to assess drug
adherence and drug therapy
 Medication possession ratio
(MPR) from computer refill
records defined as the number
of days supply of drug the
patient received over the 6-
month period
Pilot Project
 MPR (intervention vs. control): 6
months: 0.811 vs. 0.659,
(p<0.005)
 Percent continuing therapy
beyond 3 months (intervention vs.
control): 0.811 vs. 0.659 (p<
0.005)
Study
 MPR (intervention vs. control) at
6 months: 0.83 vs. 0.77

12
25. Rickles N et
al. (2005)
Depression  N=63
 Telemonitoring group
(PGEM) vs. Usual Care
(UC)
 6 months
 8 community pharmacies in
Wisconsin
 Community Pharmacists
Placed 3 monthly telephone
calls to assess knowledge of
antidepressants, adverse
effects, and treatment goals
Percent non-adherence measured
from pharmacy records and self-
report of adherence within past 7
days. Patients were asked to
answer the question “in the past 7
days ending yesterday, how many
times did you miss taking a pill?”
which is based off of an item in the
validated Brief Medication
Questionnaire.

Percent non-adherence at 6
months (PEGM vs. UC): 30.3 vs.
48.6 (p ≤ 0.05)
 Self-reported adherence: no
difference between groups
26. Capoccia KL
et al. (2004)
Depression  N=74
 Enhanced care vs. Usual
care
 1 year
 University of Washington
Medical Center
 Clinical pharmacist
Provided weekly telephone
calls for the first 4 weeks,
followed by phone contact
every 2 weeks through week
12, then every other month
from months 4-12 to
address depressive
symptoms and medication-
related concerns
Medication adherence measured
by self-reported number of days
taking antidepressant medication
in past month (percent of patients
adherent ≥ 25 days/past 30 days),
which has shown excellent
agreement between questions
regarding the use of
antidepressants in the past month
and refill records in previous
studies.
No change in adherence between
groups
Asthma and COPD
27. Weinberger
M et al. (2002)
Asthma and
COPDc
 N=447
 Control (C) vs. usual care
(UC) vs. pharmaceutical
care (PC)
 1 year
 36 Indianapolis chain
drugstores
 Community Pharmacists
PC: Provided techniques to
measure peak flow, study
materials, handouts, and
resources, and reinforced
adherence. PEFR values
were reported during
monthly phone calls to
research personnel.
UC: Patients received
neither peak flow meters nor
instructions on their use
C: Patients received peak
flow meters and instructions
on their use but PEFR
values were not reported to
pharmacist
Proportion of non-adherence over
the previous month using:
 Inui self-reporting instrument
 Morisky 4-item scale
No difference in self reported
adherence*
Helicobacter Pylori Infection

13
28. Lee M et al.
(1999)
Helicobacter pylori
infection
 N=125
 Enhanced compliance
program (ECP) vs. control
group
 14 days
 4 ambulatory health centers
in MA
 Pharmacists
Provided initial counseling,
written information,
demonstrated medication
calendar and pillbox, and
made follow-up telephone
calls at least 3 days after
therapy initiation
Numbers of patients able to
complete 60% or more and 90% or
more of the 2-week regimen based
on pill counts

No difference in percent of
patients taking > 60% of
medication (ECP vs. control): 95
vs. 89
 Percent of patients taking > 90%
of medication (ECP vs. control):
89 vs. 67 (p<0.01)
29. Stevens VJ
(2002)
Helicobacter Pylori
infection
 N=333
 Usual care vs. counseling
and follow-up
 3 months
 Health Maintenance
Organization in Portland,
OR
 Pharmacists
Provided 15 minute
counseling sessions
including side effects,
importance of completing
regimen, possible barriers to
adherence and coping
strategies, follow-up call 2-3
days after start to check on
adherence. Participants
were then contacted 8 days
after start of medication
regimen and asked to report
adherence to the current
regimen and symptoms.
Self-reported percent of
participants missing ≥1 doses of
each component of the regimen
measured 8 days after treatment
start. The questionnaire used was
not validated.
No difference in percentage of patients
missing any component of the regimen
Diabetes Mellitus
30. Odegard PS
et al. (2005)
Diabetes Mellitus  N=77
 Usual care vs. Pharmacist
intervention
 1 year
 8 clinics in the greater
Seattle, WA area
 Clinical Pharmacists
As part of a diabetes care
plan, conducted weekly in-
person or telephone
meetings then monthly after
predetermined progress with
plan was reached
Self-reported: number of missed
medication doses over the last 2
weeks using 2-question recall
technique validated in a chronic
disease model.

Percent of patients reporting
missing medication doses
(intervention vs. control): 56 vs.
35
 Self-reported adherence* in
pharmacist intervention group
was not better than usual care
group
31. Grant RW et
al. (2003)
Diabetes Mellitus  N=232
 Pharmacist intervention vs.
control
 3 months
 Community health center
near Boston, MA
 Pharmacists
Addressed adherence and
adherence barriers via initial
phone interview, performed
assessment of adherence,
and provided drug-specific
education, sent E-mail to
primary care provider
summarizing discrepancies
and adherence barriers
Self-reported adherence measured
as number of adherent days out of
past 7 days, which has shown in
prior research to have a good
correlation with electronic
monitoring.
Self-reported adherence* rates high at
baseline for both groups and did not
change
Other Chronic Medications

14
32. Solomon DK
et al. (1998)
Hypertension and
COPDc
 N=231
 Traditional pharmacy care
vs. pharmaceutical care
 6 months
 10 Veteran’s Affairs medical
centers and 1 university
hospital throughout the
United States
 Clinical Pharmacy
Residents
Focused on symptom
control, patient adherence,
drug product selection, use
of resources, patients’
satisfaction with care,
disease and disease
management knowledge,
and quality of life issues in 6
monthly visits
 Four item self-reported
adherence measure by
Morisky et al.
 Tablet counts when
medications were brought to
visits

Hypertension
Self-reported adherence*
(treatment vs. control): 0.23 vs.
0.61 (p< 0.05)
 COPD
No change in self-reported
adherence (no data provided)
 Tablet count results not provided.
33.& 34. Murray
MD et al.
(2007 & 2004)
Heart Failure  N=314
 Pharmacist intervention (PI)
vs. Usual care (UC)
 1 year
 Inner-city ambulatory care
practice in Indianapolis, IN
 Clinical Pharmacist
Nine-month pharmacist
intervention provided
patient-centered verbal
instructions and written
materials about medications
and monitored patients’
medication use, healthcare
encounters, and body
weight, followed by 3-month
follow-up period.
 Medication adherence
tracked by using electronic
monitors to compute taking
adherence and scheduling
adherence
 Refill adherence measured
by medication possession
ratio (medication received
relative to amount prescribed)
obtained from prescription
records
 Self-reported adherence
using Inui and Morisky
questionnaires

At end of intervention (UC vs. PI):
Taking adherence: 67.9%
vs.78.8% (CI 5.0-16.7)
Scheduling adherence: 47.2% vs.
53.1% (CI 0.4-11.5)
 After 3 month follow-up period
(UC vs. PI):
Taking adherence: 66.7% vs.
70.6% (CI -2.8-10.7)
Scheduling adherence: difference
48.6 vs. 48.9 (CI -5.9-6.5)
 1 year refill adherence: 105.2%
vs.109.4% (p< 0.05)
Error!
Bookmark not
defined. Nietert
PJ et al. (2009)
Chronic Disease
Medications
 N=3048
 Patient telephone (PP)
contact vs. Physician fax
contact (FP) vs. usual care
(UC)
 9 months
 9 pharmacies within a
medium-sized grocery store
chain in South Carolina
 Community Pharmacists
(PP) arm provided
telephone calls to overdue
patients asked why,
reminded them on
importance of taking
medication, and helped the
patient find ways to
overcome barriers. (FP) arm
provided physicians with
written prompts to assist
patients with persistence
Refill persistence from
administrative pharmacy data
identifying patients who were ≥ 7
days overdue (index date) and
defined as number of days from
index date to next date of next
prescription refill
No significant difference in adherence
by treatment arm
36. Faulkner et
al. (2000)
Patients
undergoing
coronary artery
revascularization
and on lipid
lowering therapy
 N=30
 Telephone contact vs. no
telephone contact
 2 years
 Cardiac Clinic in Omaha,
NB
 Clinical pharmacist
Telephoned patients weekly
for 12 weeks - Emphasis
placed on importance of
therapy, and patients
questioned on specific
reasons for non-adherence
when applicable
Non-adherence defined as
 Short term: Returning >20%
of prescribed pills at week 6
and 12 visits (pill and packet
counts)
 Long term: Failing to fill ≥
80% of prescriptions at 1 and
2 years (pharmacy refill
records)

Short term adherence: No
significant difference
 Long term adherence: 63%
telephone contact vs. 39% no
telephone contact for lovastatin
48% telephone contact vs. 23%
no telephone contact for
colestipol (p<0.05)
Prospective Cohorts

15
Tuberculosis
37. Tavitian SM
et al. (2003)
Latent Tuberculosis
Infection (LTBI)
 N=294
 No control group
 8 years
 Ambulatory care health
center in Los Angeles, CA
 Clinical pharmacists
Pharmacist managed clinic
for hospital employees with
LTBI. First visit included
discussion of importance of
adherence, then by
appointment at months 1, 2
and 3 to reinforce
Telephone interviews on
months 4-9. Non-adherent
patients were telephoned 2-
4 times a month until
reached
Completion rate determined by
number of health care workers
who completed course of LTBI
therapy divided by number of
workers monitored in the clinic
Pharmacists managed clinic improved
treatment completion rates. (Authors
finding no statistical data provided)
Chronic Medications
38. Berringer R
et al. (1999)
Diabetes Mellitus  N=3867
 No control group
 1 year
 2 independently owned
community pharmacies in
Richmond, VA
 Community Pharmacists
Monitoring by staff
pharmacists including
patient education, patient
concerns at point-of-
dispensing
Chart review by staff and
clinical pharmacists.
Medication adherence rate
calculated by dividing actual days
supply by the prescribed days
supply using prescription refill
records

Mean adherence rates:
Year prior to program: 88.1% ±
19.1%
 During study year: 90.3% ± 16.3%
39.& 40. Bluml
et al. (1998 &
2000)
Hyperlipidemia  N=397
 No control group
 Average period of 24.6
months
 26 community pharmacies &
ambulatory care pharmacies
in 12 states
 Community and clinical
Pharmacists
Collaborative practice model
including private/semiprivate
consultation areas,
technician support,
documentation systems,
and point-of-care testing
technologies. Follow-up
visits scheduled every
month for 3 months then
quarterly thereafter
Number of patients who did not
miss doses for ≥ 5 days or miss a
scheduled refill visit by more than
5 days divided by total number of
patient visits
90.1% adherence rate at end of study
Retrospective Cohorts
HIV/AIDSa

16
41. Gross R et
al. (2005)
HIV/AIDSa  N=110
 3 refill mechanisms: monthly
pick-up at hospital
pharmacy vs. monthly mail
order vs. pharmacist-
dispensed pill organizers
every 2 weeks
 3 months
 VA Medical Center HIV
clinic in Philadelphia, PA
 Clinical pharmacists
Dispensed pill organizers to
patients with suspected or
documented poor
adherence every 2 weeks,
telephoned if prescriptions
were not picked up at drop-
off/mail order pharmacies
Adherence over previous 3 months
defined as: (the number of pills
dispensed divided by number of
pills prescribed per day)/(number
of days between refills) multiplied
by 100
Good adherence defined as 85%
or greater

Percent Adherence:
Mail order vs. pick up: 91 vs. 80
(p< 0.05)
Pill organizer vs. pick up: 99 vs.
80 (p< 0.05)
Mail order vs. pill organizer: 91
vs. 99 (p=0.14)
 Proportion w/ good adherence:
Mail order vs. pick-up: 61% vs.
39% (p < 0.05)
Pill organizer vs. pick-up: 100%
vs. 39% (p<0.001)
Mail order vs. pill organizer: 61%
vs. 100% (p< 0.05)
Tuberculosis
42. Hess K et al.
(2009)
Latent Tuberculosis
infection (LTBI)
among college
students
 N=348
 No control group
 9 months
 LTBI Clinic in CA university
 Clinical Pharmacists
Counseled on importance of
treating LTBI and
encouraged patients to
complete therapy
Successful completion:
taking 270 tablets in a 9-12 month
period
6-month completion: taking 180
tablets in a 6-month period
Assessed by pharmacists’ counts
or self-reported if vial not available

Successful completion rate 6
month: 67% vs. 9 month: 59%
Case Controlled Studies
Hypertension
43. Vivian EM
(2002)
Hypertension  N=56
 Pharmaceutical care group
vs. control group
 6 months
 Veteran’s Affairs Medical
Center in Philadelphia, PA
 Clinical Pharmacists
Provided drug counseling
and hypertensive drug
therapy changes during
monthly visits
Non-adherence: Percent forgetting
to take at least 1 dose within past
week (self-reported using a
questionnaire that was not
validated) or failure to refill drugs
within 2 weeks after the scheduled
refill date (refill records)
No significant difference in adherence
HIV/AIDSa
44.
Visnegarwala F
et al. (2006)
HIV /AIDSa in
HAART naïve
women
 N=74 women
 Adherence Coordination
Services (ACS) group vs.
Directly Delivered Therapy
(DDT) group vs. Standard of
Care (SoC) group
 6 months duration
 HIV clinic in Houston, TX
 Pharmacists
ACS group received
reminder calls for pharmacy
refills. DDT had medications
delivered to them
7-day self-reported adherence for
ACS group using a self report
questionnaire and number of
empty bubble packs for DDT group
Adherence; ACS: 81% of 11 women
on HAART had 100% self-reported
adherence. DDT: 85% average level
of adherence. SoC: Not measured

17
45. Hirsch JD et
al. (2009)
HIV/AIDSa  N=1353
 Pilot pharmacy group vs.
other pharmacy group
 1 year
 10 HIV/AIDS specialty
community pharmacies in
CA
 Community Pharmacists
Managed adverse drug
reactions and side effects,
evaluated patients’ ability to
adhere to medication
regimens, tailored drug
regimens to accommodate
specific patient needs
Medication possession ratio equal
to the sum of the number days
supply of ART medication for 1
year divided by 365.25 days
 Non-adherent: <50%
 Partially adherent: 50-79%
 Adherent: 80-120%
 Excess fills: >120%
Adherence (Pilot vs. Other):
Non-adherent: 12.3 vs. 9.3 (p=0.001)
Partially adherent: 11.7 vs. 7.8
(p<0.001)
Adherent: 56.3 vs. 38.1 (p<0.001)
Excess fills: 19.7 vs. 44.8 (p<0.001)
46. Lentz N et al.
(2007)
HIV/AIDSa  N=50
 Refill Assistance Monitoring
Program (RAMP) vs. non-
RAMP
 6 months
 BioScrip Pharmacy in
Milwaukee, WI
 Community pharmacists
Implemented RAMP, a
telephone-based refill
reminder program where the
pharmacy contacted
patients 5 days before their
medications were due to
assess medication
management issues and
schedule the refill and
delivery of medication
Medication Possession Ratio
(MPR) measured by pharmacy
refill records calculated by dividing
the total number of days supply for
all fills minus the days supply of
last fill by the number of days
between first and last fill

Mean MPR’s:
RAMP: 1.03 vs. Non-RAMP: 0.86
 >=85% adherence rates:
RAMP: 96% vs. Non-RAMP: 60%
 >=95% adherence rates:
RAMP: 92% vs. Non-RAMP: 32%
Other Chronic Medications
47. Bozovich et
al. (2000)
Hyperlipidemia  N=205
 Lipid clinic vs. control group
 6 months
 Lipid clinic in Greensboro,
NC
 Clinical Pharmacists
60 minute initial visit which
included evaluation of
barriers of adherence,
followed by weekly 30-
minute visits for
reinforcement
Percent adherence defined as
refilling a prescription within 3 days
of when it was due to be refilled,
measured by direct patient
questioning and analysis of local
pharmacy refills

80% adherence with drug changes
and laboratory visits at 9 months.
 Medication adherence was not
reported separately from laboratory
visit compliance.
Other
Hypertension
48. Lai LL (2007) Hypertension  N=103
 No control group
 9 months duration
 Community pharmacy in
South Florida
 Community Pharmacists
Community pharmacy-
disease management
program where pharmacist
measured blood pressure,
provided consultation to
patients
Percent of patients who refilled
medications on time.

Percent of patients getting refills on
time at: 1 month: 71.2%, 3 months
82.7%, 6 months 88.5%, 9 months
95.7%
 Compared to baseline 70.6%, after
9 months 95% of participants
renewed their prescriptions on time
(p< 0.05)
a. Human Immunodeficiency Virus/ Acquired Immune Deficiency Syndrome
b. Highly active anti-retroviral therapy
c. Chronic obstructive pulmonary disease
*Self-reported Adherence via a validated method