Foundations and Essentials for the Doctor of Nursing Practice

Patient Education and Counseling 101 (2018) 1175–1192

Review article

Pharmacist-nurse collaborations in medication adherence-enhancing interventions: A review

Jennifer Celioa,b, Françoise Ninanec, Olivier Bugnona,b, Marie Paule Schneidera,b,* aCommunity Pharmacy, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Switzerland bCommunity Pharmacy, Department of Ambulatory Care & Community Medicine, University of Lausanne, Switzerland cDepartment of Ambulatory Care and Community Medicine, Lausanne University Hospital, Lausanne, Switzerland

A R T I C L E I N F O

Article history: Received 3 August 2017 Received in revised form 13 December 2017 Accepted 30 January 2018

Keywords: Medication adherence Patient compliance Patient adherence Pharmacists Nurses Interdisciplinary communication Interprofessional relations Collaborative care Patient care team Teamwork

A B S T R A C T

Objectives: Healthcare providers play an important role in addressing medication adherence. Pharmacists and nurses are qualified in this field even though they have different expertise. They both claim their role at the patient’s side in collaboration with physicians. To avoid care duplication, such interprofessional collaborations must be carefully defined. The objectives of our review were to: 1) identify medication adherence-enhancing interventions involving pharmacists and nurses; 2) describe their respective roles. Methods: Literature searches were conducted in PubMed/Medline, Embase, Cochrane Library. Screening criteria were: medication adherence-enhancing interventions, at least a pharmacist and nurse collaborating with/without other healthcare professionals, role description, outpatient settings, at least one oral treatment, adult patients. Results: After screening, 21 references fulfilled the inclusion criteria. Pharmacists and nurses were both in a strategic position to identify eligible patients for adherence interventions, to assess and promote adherence. Pharmacists specifically ensured treatment efficacy, security and access, they provided information on the medication and related lifestyle advice. Nurses clinically co-managed patients with physicians; they also provided patients with information on their disease. Conclusions: Pharmacist-nurse medication adherence-enhancing interventions are rare and often in a nascent phase. Practice implications: The results of our review should help in designing new pharmacist-nurse medication adherence-enhancing interventions.

© 2018 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1176 1.1. Medication adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1176 1.2. Collaboration between healthcare providers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1176 1.3. Aim of the review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1176

2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177 2.1. Database search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177

2.1.1. PubMed/MedLine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177 2.1.2. Embase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177 2.1.3. Central cochrane library . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177

2.2. Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177 2.3. Review process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177

3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177 3.1. Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177 3.2. Characteristics of the identified pharmacist-nurse interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1178

Contents lists available at ScienceDirect

Patient Education and Counseling

journal homepage: www.else vie r .com/ locate /pateducou

* Corresponding author at: Community Pharmacy Research Unit, Pharmacie de la Policlinique Médicale Universitaire, 44 Rue du Bugnon, Lausanne 1011, Switzerland. E-mail address: [email protected] (M.P. Schneider).

https://doi.org/10.1016/j.pec.2018.01.022 0738-3991/© 2018 Elsevier B.V. All rights reserved.

1176 J. Celio et al. / Patient Education and Counseling 101 (2018) 1175–1192

3.3. Medication adherence, clinical and economic outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1178 3.4. Pharmacists’ and nurses’ areas of expertise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1188

3.4.1. Pharmacists’ and nurses’ common areas of expertise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1188 3.4.2. Pharmacists’ areas of expertise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1189 3.4.3. Nurses’ areas of expertise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1189

3.5. Communication and information exchange between professionals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1190 4. Discussion and conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1190

4.1. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1190 4.2. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1190 4.3. Practice implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1191 Conflict of interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1191 Financial support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1191 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1191

1. Introduction

1.1. Medication adherence

Medication adherence is defined as “the extent to which a person’s behavior—taking medication, following a diet, and/or executing lifestyle changes—corresponds to agreed recommenda- tions from a healthcare provider” [1]. Medication adherence comprises three elements: initiation, implementation and discon- tinuation [2]. Briefly, “initiation” refers to the first dose taken, “implementation” refers to the extent to which a patient’s actual dosing corresponds to the prescribed dosing regimen and “discontinuation” refers to the interruption of treatment [2]. Persistence is another important concept and is defined as the length of time between initiation and discontinuation [2]. It is estimated that approximately 50% of chronic patients worldwide adhere to their treatment [1]. This suboptimal medication adherence of patients leads to poor clinical outcomes, increases mortality and generates economic loss [3–6]. Healthcare profes- sionals (HCPs), particularly physicians, pharmacists and nurses, play an important role in identifying patients with suboptimal adherence and in providing interventions to support and improve adherence, persistence and retention in care [1,6].

1.2. Collaboration between healthcare providers

In outpatient settings, chronic patients are usually followed by several HCPs (i.e., physicians, pharmacists, nurses and others). One of the issues of health systems is the poor, sometimes non- existent, collaboration between the different healthcare profes- sionals [7]. The discordance of the collaboration and the lack of coordination between HCPs cause disruptions in patient care [8]. Patients often triangulate between these various professionals [ 7]. Poor collaboration and communication among HCPs and between HCPs and patients may result in negative consequences, e.g., fragmentation in responsibilities, disrupted care and delayed care [9].

In 2013, the World Health Professions Alliance (WHPA) published a statement on collaborative practice [10]. Effective collaborations can lead to the following: an improved coordination between health professionals, patients and families, the opportu- nity for patients to take part in medical decisions [10], a safer health system [10], an increase in health professionals’ satisfaction [10,11] and a better use of resources [10,11]. Finally, effective collaborations can improve patients’ satisfaction [12], increase the quality of care [13] and patients’ quality of life [11].

Furthermore, collaborations among HCPs might have a positive impact on overall patient medication adherence and achievement of treatment goals. However, the evidence supporting this is still limited [14].

In the literature, the terms “interdisciplinary collaboration”, “interprofessional collaboration”, “multidisciplinary collaboration” and “multiprofessional collaboration” are not clearly defined and are often used interchangeably. “Interdisciplinary collaboration” was defined by Stone et al. in the 1970s as “when interprofessionalism emerged from the evidence suggesting that lives could be saved with better coordination and collaboration in the health services” [15]. Interdisciplinarity is best seen as bringing together distinctive components of two or more disciplines [16]. A discipline is a body of knowledge. For example, psychiatry, general medicine, infectiology are disciplines in the strict sense [17].

A profession is the association of one or more discipline(s) combined with skills (complex know-how in given situations). The profession justifies remuneration and provides a social position [11].

The term “interdisciplinary” is widely used by researchers and practitioners [15]. In recent years, the term “interprofessional collaboration” gained importance. According to the World Health Organization (WHO) [18], the “interprofessional collaboration” includes two aspects: an interprofessional education that leads to an interprofessional patient-centred collaboration. An interpro- fessional education exists when two or more professionals have a common training; they learn how to collaborate with each other, which then improves the quality of care [19].

The prefixes “multi” and “inter” define the intensity of the collaboration. “Inter” characterizes the integration of different HCPs’ knowledge and expertise, which implies strong interactions, spaces for dialogue and exchange of knowledge [11,20]. The team is a structured entity with a common goal and a common decision- making process [11,20]. “Multi” is used when HCPs work on the same project but independently or in parallel; they coordinate themselves but may not meet [11,20]. Fig. 1 illustrates the ““multi (left) and ‘inter-’ (right) collaborations (see Fig. 1).

1.3. Aim of the review

Physicians take medication adherence into consideration to refine the diagnosis and the treatment, for example they can decide to involve patients in shared decision making before initiating a medication. Alongside the prescription of long-term treatments, physicians need information on medication imple- mentation and persistence in order to ensure treatment efficacy and patient security. We postulate that pharmacists and nurses are in strategic positions to ensure continuity in care beyond the medical visit, to assess and reinforce medication adherence as a continuum and report to physicians. Pharmacists are particularly skilled in reinforcing patients’ behaviours with medication and nurses in escorting changes in various patients’ lifestyle behav- iours. Hence, to address the specific needs of chronic patients in new care models, pharmacists and nurses are both qualified to assess and support medication adherence but with different

Fig. 1. Multi- collaboration (left) and inter- collaboration (right) of healthcare providers around the patient. Based on the concept of: 1. de la Tribonnière X. L'interdisciplinarité en éducation thérapeutique du patient: du concept à une proposition de critères d'évaluation. Educ Ther Patient. 2013;5[1]:163-76. 2. Choi BC, Pak AW. Multidisciplinarity, interdisciplinarity and transdisciplinarity in health research, services, education and policy: 1. Definitions, objectives, and evidence of effectiveness. Clin Invest Med. 2006;29 [6]:351-64.

J. Celio et al. / Patient Education and Counseling 101 (2018) 1175–1192 1177

expertise [5,21]. The objectives of our review were as follows: 1) to identify medication adherence-enhancing interventions involving both pharmacists and nurses, and 2) to describe the specific roles of pharmacists and nurses in these medication adherence- enhancing interventions. Medication adherence-enhancing inter- ventions (hereinafter referred as interventions) aim to reinforce and improve patient’s medication adherence.

2. Methods

2.1. Database search

Literature searches were conducted in PubMed/MedLine, Embase and Central Cochrane Library. The searches were restricted to articles written in English or French and published from January 1996 to November 2016. The focus of these searches were articles encompassing the concepts of “medication adherence”, “interdis- ciplinary collaboration”, “interprofessional collaboration”, “multi- disciplinary collaboration” and “multiprofessional collaboration”, as these concepts have gained importance and significance during the past 20 years. The literature search was conducted using the following algorithms:

2.1.1. PubMed/MedLine (“Medication adherence”[mh] OR “Patient Compliance”[Mesh:

NoExp] OR “Medication adherence”[tiab] OR “Medication compli- ance”[tiab] OR “Patient Compliance”[tiab]) AND (“Pharmacists”[mh] OR pharmacist*[tiab]) AND (“Nurses”[mh] OR “Nursing staff”[mh] OR nurse*[tiab] OR “Interdisciplinary communication”[mh] OR “Patient care team”[mh] OR “Cooperative behavior”[mh] OR “Interprofessional Relations”[Mesh:NoExp] OR interdisciplinar* [tiab] OR interprofessional*[tiab] OR multidisciplinar*[tiab] OR multiprofessional*[tiab] OR Collaborative care[tiab] OR Patient care team*[tiab] OR Teamwork[tiab]).

2.1.2. Embase ('patient compliance'/de OR ‘medication compliance'/exp OR

((Medication NEAR/3 (compliance OR adherence)) OR (Patient NEAR/3 Compliance)):de,ab,ti) AND ('pharmacist'/exp OR phar- macist*:de,ab,ti) AND ('nurse'/exp OR ‘nursing staff'/de OR nurse*: de,ab,ti OR ‘interdisciplinary communication'/de OR ‘cooperation'/ exp OR (interdisciplinar* OR interprofessional* OR

multidisciplinar* OR multiprofessional* OR “collaborative care” OR (Patient NEXT/1 care NEXT/1 team*) OR Teamwork):de,ab,ti).

2.1.3. Central cochrane library (((Medication NEAR/3 (compliance OR adherence)) OR (Patient

NEAR/3 Compliance)):ab,ti) AND (pharmacist*:ab,ti) AND (nurse* OR interdisciplinar* OR interprofessional* OR multidisciplinar* OR multiprofessional* OR “collaborative care” OR (Patient NEXT/1 care NEXT/1 team*) OR Teamwork):ab,ti.

2.2. Study selection

The abstracts/full articles that fulfilled all the following criteria were eligible for the review:

Interventions: description of the medication adherence- enhancing interventions as evaluated in clinical studies (study designs: controlled randomized clinical trials, cluster randomized trials, cost-effectiveness studies, observational studies), or ana- lysed in [systematic] reviews, or implemented in routine care. All ‘multi-’ and ‘interprofessional’ interventions were considered.

Participants: at least a pharmacist and a nurse collaborating with or without other HCPs.

HCPs: description of the pharmacists’ and nurses’ roles. Settings: outpatient settings, ambulatory care. Treatments: at least one orally administered treatment. Patients: adults (>18 years).

2.3. Review process

The first author (JC) conducted the review and a senior researcher in medication adherence (MPS) validated each step. The other coauthors (FN, OB) did not participate in the literature review but they participated in the clarification of the theoretical concepts related to the HCPs collaborations.

3. Results

3.1. Study selection

The electronic search resulted in 1160 citations, of which 275 duplicates were identified and discarded. Of the 885 citations

Fig. 2. Articles screening process.

1178 J. Celio et al. / Patient Education and Counseling 101 (2018) 1175–1192

eligible for screening, 66 abstracts fulfilled the inclusion criteria and the full articles were reviewed. In the end, 21 references [ 22–42] (14 articles and 7 conference abstracts) were retained. The screening process is described in Fig. 2.

3.2. Characteristics of the identified pharmacist-nurse interventions

The designs of the 21 identified references were as follows: five randomized controlled trials (RCTs) [22–25,33] (of which there was one cost-effectiveness analysis [33]), one non-randomized clinical trial [26], five single-group intervention studies [28–32], and ten routinely implemented interventions [27,34–42]. The interventions were led by pharmacists, nurses and physicians [ 23,24,27,28,32–34,36,38–41]; pharmacists and nurses [24,26,31]; hospital pharmacists, nurses and psychologists [29]; pharmacists, nurses, and other healthcare professionals [30,35,37,42]. The characteristics of the reviewed studies and interventions are presented in Table 1.

3.3. Medication adherence, clinical and economic outcomes

Of the 21 identified interventions, 16 measured or planned to measure medication adherence [22–34,38,39,41] and 11 assessed or planned to assess clinical outcomes [22–26,28–31,33,39]. Only 12 interventions focused primarily on medication adherence [ 22,25–27,29,32–34,38–41]. Ten interventions did not provide any adherence or clinical results [31,32,34–38,40–42].

Only 4 studies demonstrated improvements in both medica- tion adherence and clinical or economic outcomes [25,26,30,33].

A RCT [25] showed a difference in medication adherence (median post hoc adherence composite index of 1.36 vs. 1.00 in the control group, p = .008) associated with better clinical outcomes in the intervention group. The change in the mean 24- h ambulatory blood pressure was larger (SBP: �11.9 vs. �7.1 mmHg, p < 0.001, DBP: �6.6 vs. �4.5 mmHg, p = .007) in the intervention vs. the control group, and more subjects in the intervention group achieved the target blood pressure (46.0% vs. 28.6%, p = .006) [25]. In a single group intervention study [30], self-assessed adherence (measured by the Morisky question- naire) improved at 3 months (3.16 � 0.95 vs. 2.91 �1.03 (baseline), p < 0.1, n = 159) and sustained at 6 months (3.13 � 0.90 vs. 2.85 � 1.01 (baseline), p = .2, n = 103); physical health scores improved at 3 months (38.44 � 11.39 vs. 36.99 � 10.25 (baseline), p = .01, n = 169) but not at 6 months (36.96 � 10.94 vs. 35.94 � 10.38 (baseline), p = .29, n = 104) [30]. In a non-randomized trial [26], adherence increased in both groups (Ig 71% to 80%, p = .006, Cg 72% to 87%, p < .001); however, patients in the intervention group had 55% higher probabilities to achieve blood pressure control (OR = 1.559, 95% CI [1.082–2.245], p = .017) and 13% higher probabilities to achieve glycaemic control (OR = 1.134, 95%CI [0.8545–1.506], p = .383) [26]. Cost-effectiveness analysis [33] showed that adherence and sustained virological response rates to hepatitis C are higher in the intervention group than in the control group (p < 0.05). Moreover, the cost-savings per patient in the intervention group was s2476, and QALYs per patient increased by 0.622 (for genotypes 1 or 4) and s1471 + 0.208 QALYs (for genotypes 2 or 3) [33].

Table 1 Characteristics of the 21 Reviewed Articles.

Design Program Setting, Nr patients. (Intervention group (Ig)/Control group (Cg))

Path. Program duration

Types of Intervention Pharmacists’ role Nurses’ role Outcomes Adherence measure instrument

Main results

Randomized controlled trial (RCT)

Leiva et al. [2014] Spain

28 primary care centers, Balearic Islands, Aragon, Catalonia, Spain (Ig: 114/Cg: 109) Ig: multifactorial intervention Cg: no change in their care.

HBP 12 months Multifactorial intervention (pharmacist + nurse) 1) Motivational interview 2) Pillbox reminder 3) Family support 4) BP measurement 5) Simplification of dosing

regimen

Freq: at 1m, 3m and 9m Team meetings: N/A

1) Supervision of each patient’s treatment and dosage

2) Simplification of the dosing regi- men at the first follow-up visit, when possible

Motivational interview

1) Systolic BP at 12m 2) Diastolic BP at

12m 3) Proportion of par-

ticipants with ad- equate BP control at 12m (European Society of Hyper- tension/Society of Cardiology guide- lines)

4) Medication ad- herence

Medication refills (MPR of a randomly chosen antihypertensive drug during 6m)

� Systolic BP: 151.3 Ig vs 153.7 Cg (P = .294)

� Diastolic BP 83.4 Ig vs 83.6 Cg (P = .917)

� 15.8% Ig achieved BP control vs. 9.2% Cg (p = .098). RR = 1.72 (95%IC: 0.83–3.56)

� Adherence to antihy- pertensive therapy: 75.3% Ig vs. 76.7% Cg. Adh <80% in 51.4% Ig vs 50.8% Cg.

Randomized controlled trial (RCT)

Carrion et al. [2013] Spain

Liver unit, Gastroenterology Department, Hospital del Mar, Universitat Autonoma de Barcelona, Spain Pts were divided into 3 groups: Cg: pts receiving treatment from 2003 to 2004with a standard follow-up Ig (MSP group): pts included from 2005 to 2006 in the program MSP- validation group: pts from 2007 to 2009 to validate the efficacy of the MSP. (131 (Ig)/169 (MSP validation)/147 (Cg))

HCV 48 weeks + 24 weeks after treatment completion

A multidisciplinary support program (MSP) to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in chronic hepatitis C (CHC) (pharmacist + nurse + physician) Freq: at baseline, 2, 4, 12, 24 and 48 weeks during treatment and 24 weeks after treatment completion Team meetings: weekly

1) Medication ad- herence assess- ment

2) Reinforcement of the medica- tion instruction

3) Recording of the drug doses

4) Promotion of medication ad- herence

1) Complete and standardized in- formation re- garding HCV (epidemiology, natural history, diagnosis and follow-up)

2) Information about the anti- viral treatment (type of drugs, doses, adminis- tration adverse effects)

1) Medication ad- herence

2) Sustained virolog- ical response (SVR)

3) QALY

Assessed by the pharmacist as a % using a daily self- reported questionnaire related to the number of pills and injections.

Adherence (>80% of each drug) and SVR (undetectable viral load 24 weeks after the end of the treatment) rates higher in Ig (94.6% and 77.1%) and MSP- validation groups (91.7% and 74.6%) compared to Cg (78.9% and 61.9%) (P< 0.05 in all cases) (all patients) � The Ig (compared to

Cg) saved s2476 and increased 0.622 QALYs per patient (genotypes 1 or 4), and saved s1471 and increased 0.208 QALYs per patient (genotypes 2 or 3).

The multidisciplinary support program group met weekly to evaluate the degree of motivation & adherence

Randomized controlled trial (RCT)

Pyne et al. [2011] HITIDES study (HIV Translating Initiatives for Depression Into Effective Solutions) United States

3 Veterans Affairs HIV clinics (Central Arkansas Veterans Healthcare System, Michael E. De Bakey VA Medical Center, Atlanta VA Medical Center), United States (Ig: 123/Cg: 126) Ig: support of the HITIDES team Cg: usual care (within the

HIV and

depressive disorder

12 months Practice-based collaborative care An offsite HIV depression care team delivered a collaborative care backed by a Web-based decision support system (nurse depression care manager + clinical pharmacist + psychiatrist) Freq: monitoring by the nurse every 2 weeks during acute treatment (before achieving a sustained 50% decrease in the

Review of depression treatment history

Telephone-based monitoring 1) Education and

activation 2) Assessment of

treatment bar- riers and possi- ble resolutions

3) Practical help to reintegrate so- cial life

1) Depression sever- ity

2) Treatment re- sponse, remission and depression- free days

3) Health-related quality of life

4) Health status 5) HIV symptom se-

verity 6)

AIDS Clinical Trial Group assessment questionnaire (participants reported the number of skipped doses for each antiretroviral medication for each of the past 4 days)

� Significant differ- ences were as fol- lows:

� More depression- free days during the 12 months (b = 19.3; 95% CI, 10.9–27.6; P< .001).

� Lowering HIV symp- tom severity at 6 months (b =�2.6; 95% CI, �3.5 to �1.8; P < 0.001) and 12

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Table 1 (Continued)

Design Program Setting, Nr patients. (Intervention group (Ig)/Control group (Cg))

Path. Program duration

Types of Intervention Pharmacists’ role Nurses’ role Outcomes Adherence measure instrument

Main results

involvement of the HITIDES team)

9-item Patient Health Questionnaire (PHQ-9) depression score), every 4 weeks during watchful waiting or continuation treatment (PHQ-9 score <5) or 6 months after maintaining a 50% decrease in the PHQ-9 score Team meetings: once a week or as needed

Antidepressant or HIV medication adherence

months (b =�0.82, �1.6 to �0.07, P=0.04).

� Intervention effects were not significant for other secondary outcomes

Both pharmacists and nurses: treatment suggestions, pharmacotherapy and specialty mental health counseling

Randomized controlled trial (RCT)

Wang et al. [2010] Taiwan

Pulmonary Medicine outpatient clinic (Tri-Service General Hospital, Taipei, Taiwan) (35 (Gr.1)/34 (Gr.2)/32 (Gr.3)) Group 1: nurse- administered education program Group 2: education program (nurse) with an additional pharmacist counseling Group 3: a control group with routine care only (control)

Asthma 3 months Asthma educational program (nurse (+pharmacist)) Freq: Three 1-h sessions offered during monthly clinic visits (at months 1, 2 and 3) Team meetings: N/A

For group 2: 1) Information re-

lated to the ac- tion and side effects of asth- ma medications

2) Treatment plans for individual- ized medication

3) Modification of medications in response to progressive asthma

1) Definition, eti- ology, diagnosis, disease prog- ress, and com- plications of asthma

2) Instruction to monitor disease severity (e.g. use of the peak ex- piratory flow meter);

3) Introduction on medications for asthma therapy (e.g. correct in- haler techni- ques); and

4) Guidelines for self-manage- ment

At baseline, 3 months and 6 months: 1) Asthma knowl-

edge 2) Health-related

quality of life 3) Medication ad-

herence

Self-assessed adherence (Morisky questionnaire)

� Knowledge scores in Gr. 1 and Gr.2 in- creased significantly compared to Gr.3 (Cg) � gr.1: month 3 (23.03 vs. 20.22), month 6 (20.79 vs. 21.03) all P< 0.0168 – gr.2: month 6: 23.57 vs. 21.03, P< 0.0167.

� No significant dif- ferences in medica- tion adherencewere seen among groups, even though medi- cation adherence scores for all 3 groups increased signifi- cantly with time.

Randomized controlled trial (RCT)

Rinfret et al. [2009] Canada

8 primary care clinics in Laval, Quebec, Canada. Prescriptions filled at one of the 32 participating pharmacies (Ig: 111/Cg:112) Ig: educational booklet, digital home BP monitor, log book and access to a telephone-linked IT-supported management program Cg: usual care and educational material

HBP 1 year Information technology (IT)- supported management program to facilitate BP and adherence data circulation between patients and primary healthcare providers (physician + pharmacist + nurse) Freq: the system collected self- recorded BP and self-assessed adherence data weekly. Team meetings: data and generated reports were faxed monthly to the team.

To the IT-supported central system: 1) Transmission of

data on antihy- pertensive pre- scription refill (for both groups)

2) Communication of changes in medication (for both groups)

If poor BP control after 4 weeks or report of non adherence 1) Inquiring about

BP or adherence difficulties

2) If necessary, re- ferring subjects to their physi- cian or pharma- cist

1) Change in mean 24-h, daytime and nocturnal SDP and DBP measured by ambulatory blood pressure monitor- ing (ABPM)

2) Change in office SBP and DBP measured by a digital BP moni- tor;

3) Proportion of subjects that achieved target BP

4) Medication ad- herence

Self-assessed adherence (Morisky questionnaire) and continuous medication availability (CMA) and measures of gaps (CMG) scores calculated from the pharmacy data.

� Change in the mean 24-h ambulatory BP greater in Ig vs. Cg for SBP (�11.9 versus �7.1mm Hg; P < 0.001) and DBP (�6.6 vs �4.5mm Hg; P = 0.007).

� More subjects achieved Canadian Guideline target BP in the Ig vs. Cg (46.0% vs 28.6%, P = 0.006).

� A trend toward im- proved medication adherencemeasured by prescription refills (CMA) in the Ig vs. Cg (P = 0.07)

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� Median posthoc ad- herence composite index: 1.36 (Ig) and 1.00 (Cg) (P = .008)

Non- randomized clinical trial

Mino-León et al. [2014] Mexico

2 family medicine clinics of the Instituto Mexicano del Seguro Social, Mexico (Ig: 211/Cg: 229) Ig: incorporation into the health team of 2 experienced pharmacists Cg: usual care and a brochure with “basic” information on the proper use of antihypertensive and antidiabetic drugs

Type 2

diabetes mellitus (T2DM) and/or HBP

6 months Incorporation of the pharmacist as a support member of the health team at the ambulatory health care level! to increase the proportion of patients with T2DM and/or HBP who adhere to their drug regimen. (pharmacist + nurse) Freq: a session with the pharmacist after the medical visit and 3 follow-up sessions with the nurse Team meetings: N/A

A session after the medical visit: 1) Importance of

taking each of the drugs

2) Management of missed doses

3) Management of adverse effects

4) Information about medica- tion schedules regarding food and meal times

5) Importance of diet and exer- cise

6) Reducing salt intake (if HBP)

7) Pictograms to inform regard- ing quantities, schedules and duration of each treatment

3 follow-up sessions with a nurse (at week 4 and months 2 & 3): 1) Reinforcement

of the pharma- cist’s advice

2) Pill count

1) Medication ad- herence

2) Control of T2DM (�130mg dL�1)

3) Control of HBP (� 140/90mmHg)

Pill count � Increase of adher- ence (medication use between 80%-110%) in both groups be- tween baseline and month 6 (Ig 71–80%, P = .006 and Cg 72– 87%, P = .000)

� 55% higher probabil- ity of Ig to achieve control of HBP com- pared to Cg (gener- alized linear models)

� 13% more possibility for the Ig to achieve glycaemic control compared to Cg

Single group intervention study

Rodis et al. [2010] United States

HCV education and monitoring service, Ohio, United States 17 patients

HCV 3 months Pharmacists and a nurse practitioner developed a new model of care in an HCV education and monitoring service. The study was developed to evaluate the impact of this partnership of care. (pharmacist + nurse + physician) Freq: Pharmacist: baseline and monthly follow-up phone calls Nurse: visits scheduled quarterly Team meetings: N/A

1) Initial education and training on the administra- tion and side effects associat- ed with HCV combination therapy

2) Monthly follow- up phone calls to assess side effects, make recommenda- tion to enhance tolerability of HCV medica- tions, and iden- tify serious side effects.

Follow-up visits 1) Changes in quality of life (QOL)

2) Changes in medi- cation adherence

3) Relationships be- tween medication adherence and QoL

4) Patient satisfac- tion

Self-assessed adherence (Morisky questionnaire)

� 99.8% of total inter- feron and ribavirin doses taken during the first 3 months

� Satisfaction of care as expressed by patients

Single group intervention study

Berki- Benhaddad et al. [2006] France

Bichat-Claude- Bernard Hospital, Paris, France 4 groups: Discontinuation (n = 26) Failure

HIV 12 months Specific educational and counseling intervention to examine and improve adherence (implementation and initial results) (psychologist + hospital

Simultaneously present at the first visit (40–60min). For the following visits, their respective presence was related to specific skills required for each patient (not specified). Their role 1)

At baseline, 1, 3, 9 and 12 months 1) CD4 cell counts

and HIV viral loads

2)

Visual Analog Scale (no more details in the article)

Effectiveness � Discontinuation 13/

26 (50%) � Failure 25/61 (41%) � Preparation 31/37

(84%)

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Table 1 (Continued)

Design Program Setting, Nr patients. (Intervention group (Ig)/Control group (Cg))

Path. Program duration

Types of Intervention Pharmacists’ role Nurses’ role Outcomes Adherence measure instrument

Main results

(two consecutive viral loads >200 copies/mL) (n = 61) Preparation (naive patients seen before starting the treatment) (n = 37) Reinforcement (patients seen for counseling to prevent virological failure) (n = 15)

pharmacist + nurse) Freq: N/A Team meeting: N/A

Assessment of knowledge, disease’s- and treatment’s representations

2) Assessment of the motivation 3) Supporting patients in the disease’s-

and treatment’s acceptance 4) Provision of information about the

disease and the medication 5) Monitoring medication adherence

Effectiveness of the intervention (taking,-restarting HIV regimen, vi- rological response (< 200 copies/ mL) (Medication adherence)

� Reinforcement 14/15 (93%)

Medication adherence � No data available

Single group intervention study

Farris et al. [2004] Canada

Canada, 182 patients

Complex patients

6 months A collaborative community- based care among providers distant from one another (implementation phase). 6 primary health care teams (family physicians, nurses, pharmacists, and home care case managers (nurses)). Freq: N/A Team meetings: every week (for 1.5 h) to discuss patients’ health problems Information from follow-up assessments was shared during the next team meeting Medication or health issues were identified by the team. The team then decided on actions to take or issues to monitor. Follow up was completed as necessary via telephone or in person by the appropriate provider

1) Home medica- tion reviews

2) Telephone fol- low-ups

3) Contact with patients' com- munity phar- macist if necessary

4) Documentation of each identi- fied health issue and actions tak- en by the team

1) Contact with home care case managers or

2) Direct responsi- bility for patients

1) Physical health component (at 3 and 6 months)

2) Mental health component (at 3 and 6 months)

3) No. of physician visits, hospital admissions, and emergency de- partment visits

4) Medication ad- herence

Self-assessed adherence at 3 and 6 months (Morisky questionnaire)

1) Physical health score improved at 3 months (36.99� 10.25 vs 38.44� 11.39, p = 0.01, n = 169)

2) Mental health un- changed at 3 and 6 months

3) Trend toward fewer hospital admissions, physician, and emergency depart- ment visit (37% pts visited physicians �6x compared to 50% pts 6m-before the study; pts with no emergency de- partment visits in- creased from 64.9% to 70.6%, and pts with no hospital admissions in- creased from 74.6% before the study to 79.4% 6 months lat- er)

4) Adherence im- proved at 3 months (baseline 2.91� 1.03 vs 3.16� 0.95, p< 0.001, n = 159) and sustained at 6 months (2.85� 1.01 (baseline) vs. 3.13� 0.90 (6m) p = .02, n = 103),

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Single group intervention study

Kraayenbrink et al. [2013] Conf. Abstract United States

Inde-pendent community pharmacy + community health center, Iowa, United States

HBP 6 months HBP-related care provided by a community pharmacy-based clinical pharmacist working with a clinic-based nurse practitioner to manage medication therapy through a collaborative practice agreement. Patients were seen initially by the pharmacist or nurse (pharmacist + nurse) Freq: every 2 weeks by either provider until BP goal was reached, then every 4 to 6 weeks in the maintenance stage of their therapy. Team meetings: N/A

1) Dose adjust- ments

2) Patient educa- tion

3) Use of compli- ance aid

1) BP change 2) Percentage of

patients reach- ing BP goal

3) Length of time from enrollment in clinic to reaching BP goal

4) Adherence to appointment at- tendance

5) Proportion of days covered (PDC) by medi- cation

Medication refill No results yet

Single group intervention study

Haupais et al. [2011] Conf. Abstract France

Upper Normandy (Réseau Onco- Normand), France Nr patients: N/A

Cancer Not specified

Regional information on the proper use of oral chemotherapy to improve medication adherence and experience at home (pharmacist + nurse + physician) Freq: nurse weekly patient home visit Team meetings: weekly for completing patient diary (administration, AE, patient’s comments, pharmacists, GP & community nurse comments)

1) Record of the date of delivery in a diary (to estimate medi- cation adher- ence)

2) Administration plan (oral che- motherapy and usual treat- ments)

1) Record of the number of tablets/capsules remaining in the box (in the pa- tient diary)

2) Early detection of adverse effects

3) Patient educa- tion at home

N/A Pharmacists’- and nurses’ assessment (medication refill and pills count)

No results yet

Routinely

implemented program

LelubreM. et al. [2015] Switzerland

Community Pharmacy of the Department of Ambulatory Care and Community Medicine (Policlinique Médicale Universitaire, PMU) in collaboration with Infectious Diseases Service of the Lausanne University Hospital (CHUV), Lausanne, Switzerland (between 2004 and 2014, 819 patients included)

HIV Not specified

Motivational interviewing combined with medication adherence electronic monitors (MEMS) and report that provides feedback to the patient, physician, nurse, and other pharmacists. (physician + pharmacist + nurse) Freq: First interview happens on the same day or within a few days after the patient agreed to participate. The other interviews take place 30– 45min before a medical visit, at least every 3 months. Team meetings: N/A Adherence report sent to the physician and the nurse.

1) Validation of the medical pre- scription

2) Presentation of the program and the MEMS

3) Patient’s per- sonal and psy- chosocial condi- tions

4) Therapeutic his- tory

5) Experienced barriers and facilitators to medication in- take

6) Previous adher- ence support

7) Feedback based onMEMS results

8) Semi-directed interview using the Informa- tion-Motiva- tion-Behavioral Skills model

1) Reception of the medication ad- herence report

2) Address patient’s psy- chosocial pro- blems and support patients

N/A Medication adherence electronic monitors (MEMS) and pill count

N/A

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Table 1 (Continued)

Design Program Setting, Nr patients. (Intervention group (Ig)/Control group (Cg))

Path. Program duration

Types of Intervention Pharmacists’ role Nurses’ role Outcomes Adherence measure instrument

Main results

Routinely

implemented program

Rojas- Fernandez C. et al. [2014] Canada

Centre for Family Medicine (CFFM) Family Health Team (FHT), Ontario, Canada (N/A)

Alzhei- mer and demen- tia

3,6, 9, 12 or more months

Interdisciplinary team (pharmacist + nurse + physician + social workers + others) Freq: at least every 3 months Team meetings: at every patients’ visit The team met with the physician to discuss the case, and input is provided by all team members.

1) Clinical review prior to the clinic visit

Preliminary assess- ment of comorbi- dites Medications known or suspected to have adverse cog- nitive effects 2) Assessment of

patient’s medi- cation regimen

Visual examination of blister packs, pill counts, and/or call- ing the patient’s pharmacy to ascer- tain refill history Assessment of the understanding of the medications (shared decision- making process) 3) Assessment of

adverse drug events

4) Revision of the pharmacother- apeutic plans

Cognitive testing In case of potential concerns identified by the pharmacist: 1) Collect of rele-

vant informa- tion

2) Verifications and/or clarifica- tion of this in- formation dur- ing the group discussion

3) Discussion with the caregivers/ patient dyad for further consid- eration

N/A N/A N/A

Routinely

implemented program

Hanson et al. [2014] Multiple sclerosis pharmacy practice model United States

University of Illinois Health’s department of neurology, United States

Multiple sclerosis

Not specified

Integrated clinical and specialty pharmacy service (SPS) model - Dedicated clinical pharma- cist on the team

- Integrated specialty phar- macy service

- Direct access to the elec- tronic medical record

- Face-to-face interaction with patients

(clinical pharmacist + registered nurse + neurologists) Freq: N/A Team meetings: pharma- cist + neurologist 1�/week

1) Review of the patient’s profile and assessment of the training and educational needs of the patient and family 2) Coordination of the therapy initiation and ongoing Disease Modifying Therapy (DMT) management 3) Discussion of the alternative therapies with the neurologist 4) Communi-cation to the physician of any challenge that the patient may have 5) Coordination of

Coordination of the therapy initiation and ongoing Disease Modifying Therapy (DMT) management

Medication adherence

Medication possession ratio

Adherence before (2007–2009, n = 30) and after (2010–2012, n = 167) implementation of SPS p = 0.0980 (95%IC �0.16841; 0.01441). MPR: 2007: 85% (n = 10) 2008: 88% (n = 10) 2009: 84% (n = 10) 2010: 88% (n = 34) 2011: 94% (n = 62) 2012: 93% (n = 71)

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the access to therapy and training of patients if it is dispensed outside of the health system 6) Written medical justification for use if the selected therapy is not the insurance plan’s preferred treatment. 7) Review of the appropriate use of fingolimod (administration, medications to avoid, importance of adherence, possible AE) 8) Second review of patients’ current medications

Routinely

implemented program

Bedouch P. et al. [2011] France

Pulmonary Arterial Hypertension referral centre, Grenoble, France. (N/A)

Pul- monary Arterial

Hypertension

Not specified

Multidisciplinary care teams (pharmacist + nurse + physician) Patient individual interview Freq: at least every 6 months Team meetings: Weekly Following each interview, a standardized report form with pharmacist’s recommendations (drug-related problems, drug handling and biological monitoring, medication adherence, disease understanding) is provided to physicians and nurses and discussed collaboratively.

Individual interview of 30–45minutes 1) Standardized

patient history 2) Identification of

patient’s needs and definition of educational objectives adapted to the patient’s cogni- tive level and behavior.

3) Information and explanations about:

- Aims, benefits and risks of the treatment

- Medication use and effect

- Clinical and bio- logical surveil- lance

- Drug interaction - Management of missed doses and side effects

- Disease knowl- edge and daily management

4) Reinforcement and optimizing of the patient’s

Collaborative discussion.

N/A N/A N/A

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Table 1 (Continued)

Design Program Setting, Nr patients. (Intervention group (Ig)/Control group (Cg))

Path. Program duration

Types of Intervention Pharmacists’ role Nurses’ role Outcomes Adherence measure instrument

Main results

medication reg- imen.

Routinely

implemented program

Colombo J. et al. [1997] United States

HIV clinic, University of Illinois Hospital, Chicago, United States (N/A)

HIV Not specified

Multidisciplinary health care team (pharmacist + nurse + physician + dietetician + social worker + phlebotomist Freq:N/A Team meetings: pharmacists: attended weekly patient reports

1) Medication his- tories

2) Patients’ educa- tion

3) Counseling on adherence

4) Monitoring re- sponse to thera- py

5) Drug-related problems

6) Therapeutic decisions

1) Phone calls (drug-related problems)

2) Medication refill for patients who were unable to come to clinic or who walked in without appointments

3) Took all phar- macy inquiries

N/A N/A N/A

Routinely

implemented program

LelubreM. et al. [2015] Conf. Abstract Switzerland

Switzerland (5) HIV Not specified

Multifactorial and interdisciplinary adherence program for HIV patients (pharmacist + nurse + physician) Freq: at least every 3 months Team meetings: N/A Adherence report sent to the physician and the nurse

1) Motivational interviewing

2) Treatment de- livered in elec- tronic monitors

1) Patients’ screening for the program

2) Use of the ad- herence report and discussion with the patient (patient educa- tion)

1) Medication ad- herence

2) Implementation (Re-AIM: Reach, Effectiveness, Adoption, Imple- mentation and Maintenance)

Medication adherence electronic monitors (MEMS)

N/A

Routinely

implemented program

Falkowski et al. [2015] Conf. Abstract France

France (176) Cancer 1 year Multidisciplinary approach to support patients in following their oral anticancer agents’ treatment. (physician + pharmacist + nurse) Freq: N/A Team meetings: N/A

Individual pharmaceutical counseling

Adherence assessment (telephone call after 8 days, using a survey)

1) Medication ad- herence

2) Side effects

Survey (no more details)

91 patients answered the questionnaire 1) Optimal adherence 2) 66 had side effects (48 grade 1, 28 grade 2 and 6 grade 3) Nurses provided counseling to 43 patients 14 patients requested pharmaceutical counseling

Routinely

implemented program

Lane et al. [2014] Conf. Abstract United States

Dana-Farber Cancer Institute, Boston, United States (12)

Cancer Not specified

Multidisciplinary team to address patient safety risks associated with oral chemotherapy use (patient education and adherence monitoring) Physicians, Nurse Practitioners or Physician Assistants initiate education by reviewing the dosing schedule, side effects and by providing a standard education sheet. (physician + pharmacist + nurse) Freq: N/A Team meeting: N/A

Within 24 h, teaching session utilizing a template based upon the MOATT Tool (teaching tool developed by the Multinational Association of Supportive Care in Cancer): 1) review of the

dosing schedule 2) side effects and

management

Within 5 days: call to 1) Reinforce edu-

cation 2) Assess toxicity 3) Assess adher-

ence

Patient satisfaction N/A N/A

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3) drug handling 4) drug/food inter-

actions 5) practice contact

details for ques- tions

Routinely

implemented program

Bourdin A. et al. [2013] Conf. Abstract Switzerland

Switzerland (N/A) Multiple sclerosis (MS)

Not specified

Person-centred and integrated care program (using a secured web-platform (SISPha SA) as a vector of collaboration and monitoring) (pharmacist + MS nurse+ neurologist + general practitioner (GP)) Freq: 2 weeks-3 months Team meeting: N/A

1) Medication sup- ply

2) Check for con- traception methods in women

3) Information on management of missed doses (within the first 2 weeks and af- ter)

4) Safety remin- ders

5) Patient infor- mation (vacci- nation, attitude in case of preg- nancy)

6) Check of ful- filled or planned medical follow- up

7) Long term fol- low-up (motiva- tional inter- views to support drug safety and adherence)

1) Pre-treatment medical check- up (with neu- rologist and GP)

2) 1st dose moni- toring (with neurologist)

3) Specific MS fol- low-up (with neurologist)

Medication adherence

Medication adherence electronic monitors (MEMS)

N/A

Routinely

implemented program

Delage J. et. al. [2011] Conf. Abstract France

France OncologyNot specified

Education program by a multidisciplinary working group

(pharmacist + nurse + dietetician + physician onco-geriatric + haematologist) Freq: N/A Team meeting: N/A

1) Review of patients’ medi- cation (drug- drug interac- tions, self-med- ication evalua- tion).

2) Assessment of patient skills

3) Management of side effects of chemotherapy

N/A N/A N/A

In the table, the term “adherence” is used systematically for consistency even if other terms were used in some reviewed papers such as “compliance” or “observance (French)". (Freq = frequency of patients’ provided intervention, Team meeting = frequency of team meetings). ABPM =Ambulatory blood pressure monitoring; Adh = adherence; AE = adverse effects; AIDS = acquired immune deficiency syndrome; BP = blood pressure; CD4 = cluster of differentiation 4 (glycoprotein); Cg = control group; CHC = chronic hepatitis C; Conf. abstract = Conference Abstract; CMA = continuous medication availability; DBP = diastolic blood pressure; DMT = disease modifying therapy; GP = general practitioner; HBP = high blood pressure; HCV = hepatitis C virus; HITIDES = HIV translating initiatives for depression into effective solutions; HIV = human immunodeficiency virus; Ig = intervention group; IT = information technology; m =month(s); MEMS =medication event monitoring system; MOATT Tool =Multinational Association of Supportive Care in Cancer teaching tool; MPR =medication possession ratio; MS =multiple sclerosis; MSP =multidisciplinary support program; N/A = not applicable; PDC = proportion days covered; PHQ–9 = Patient Health Questionnaire; Pts = patients; QoL = quality of life; QUALY = quality-adjusted life-year; RR = relative risk; SBP = systolic blood pressure; SPS = specialty pharmacy service; SVR = sustained virological response; T2DM= type 2 diabetes mellitus.

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3.4. Pharmacists’ and nurses’ areas of expertise

Fig. 3 summarizes the pharmacists’ and nurses’ areas of expertise in the 21 identified interventions. Some skills were common between pharmacists and nurses but others were specific to each profession as described below.

Responsibilities were often assigned to pharmacist or nurses, but they rarely covered these responsibilities together. In addition, the roles of the pharmacists and nurses were often not clearly defined and were only partially described in the articles.

3.4.1. Pharmacists’ and nurses’ common areas of expertise

3.4.1.1. Screening, assessing and supporting medication adherence. Pharmacists and nurses played a fundamental role in screening, assessing and supporting medication adherence. Depending on the intervention, the tasks of screening, assessing and supporting medication adherence are (a) shared between HCPs or (b) assigned to a specific professional.

In three of the identified interventions [27,30,33], the responsibilities were shared between pharmacists and nurses (a). In the first intervention, the team (pharmacists, nurses, family physicians, family physicians’ office nurses and home care case managers) identified eligible patients to enter the adherence program. During team meetings, the patients’ medication

Fig. 3. Healthcare providers (e.g. physicians, pharmacists, nurses, social workers, psycho This figure focuses on the pharmacists and nurses’ areas of expertise.

histories were presented by pharmacists, and health and treatment issues were presented by physicians and nurses. The team then discussed the appropriate strategy for monitoring and addressing adherence issues [30]. In the second intervention, which was for hepatitis C patients, pharmacists and nurses assessed adherence to antiviral treatment. At the first visit, medication adherence was assessed by the pharmacist using a questionnaire; the multidisciplinary team then met weekly to evaluate the patients’ degree of motivation and adherence and to discuss the follow-up strategy [34]. In the third intervention, which was for multiple sclerosis patients, the pharmacists reviewed the patients’ medication profile and assessed the needs of the patients and their families; then, pharmacists and nurses supported medication adherence jointly by coordinating the treatment initiation and management [27].

In other interventions, the responsibilities in screening, assessing and supporting medication adherence were stronglyassociated with the specific area of expertise of either professional (b).

Pharmacists delivered the treatment to the patients [ 32,34,40,41], they educated patients on the importance of adherence during the validation of the prescription [26,33], and they assessed adherence based on medication refills [25,32,33,35]. In other advanced adherence interventions, the patients benefited from individual interviews with the pharmacist; for instance, the pharmacists assessed the patients’ adherence with their previous treatment, they identified past barriers to adherence and they

logists) play an important role in supporting and improving medication adherence.

J. Celio et al. / Patient Education and Counseling 101 (2018) 1175–1192 1189

determined whether these factors might still impair the patients’ adherence to the present treatment [37]. Likewise, nurses had the opportunity to inquire about adherence difficulties [25] and to assess treatment barriers [23]; nurses then decided either to manage these situations [23,25] or to refer patients to their pharmacists [25]. Nurses assessed adherence by a survey [39], by telephone [40] or by pill count [23,32].

In an intervention for cancer patients, responsibilities in screening, assessing and promoting medication adherence were exchanged between pharmacists and nurses as a multiprofes- sional team.The intervention incorporated information on the proper use of oral chemotherapy and the evaluation and prevention of iatrogenic effects. A patient diary for post- treatment follow-up appointments was implemented as a weekly account of the oral chemotherapy administration, adverse effects and patient’s comments, as well as the com- ments of pharmacists, general practitioners and community nurses. The patient was encouraged to share the diary with the oncologist at each visit. Information on the appropriate use of oral chemotherapy was provided to patients by nurses to promote adherence. Pharmacists recorded the date of the medication delivery in the patients’ diary, and nurses did the same during home-nurse visits; updates on the number of pills remaining in the pill box during each visit were recorded in the diary by all healthcare professionals [32].

3.4.1.2. Skills and methods for supporting medication adherence. Both pharmacists and nurses used motivational interviewing skills to support medication adherence. Using motivational interviewing skills, pharmacists supported medication adherence [34,38,41] and ensured treatment safety [41]. In another intervention, pharmacists carried out semi-structured motivational interviews based on the Information-Motivation-Behavioural Skills model [40]. Pharmacists discussed barriers and facilitators to medication intake and assessed the patients’ motivation and emotions associated with the treatment. In the same way, nurses explored non-adherence based on the Health Belief Model, resolved patients’ ambivalence regarding medication and explored patients’ perceptions on their ability to control events [22].

Pharmacists and nurses took responsibilities in ensuring patients’ education and promoting self-management. Regarding patients’ education, pharmacists evaluated patients’ treatment literacy [35,36,38], assessed patients’ educational needs regarding medication [27,36] and provided the initial education and training on medication [28]. Education provided by pharmacists mainly focused on medication, while nurses educated patients by providing information on the disease and the patient’s diagnosis, explaining how to monitor the disease severity and by giving an introduction on administering the medication. Nurses usually delivered the medication training in the healthcare settings but sometimes patients were educated at home [26].

Regarding self-management, pharmacists assessed the patients’ capacity to self-manage their treatment in daily routine [38]. In an intervention, asthmatic patients were assigned to three 1-h education sessions with a nurse, and if necessary, supple- mented with a pharmacist’s counseling session (information related to the action and side effects of asthma medications, individualized treatment plan, etc.) [24]. In another intervention for HIV and depressive patients, a depression case manager (a nurse) provided self-management instructions (e.g., encouraging patients to exercise and to participate in social activities) [23].

3.4.2. Pharmacists’ areas of expertise Pharmacists’ areas of expertise focused on 1) treatment efficacy,

security and access, 2) information on medications, and 3) lifestyle advice.

3.4.2.1. Treatment efficacy, security and access. Pharmacists ensured treatment efficacy and security. First, pharmacists had a comprehensive account of patients’ prescriptions and over-the- counter medication histories [23,36,38]. For instance, in a team delivering collaborative care to patients with HIV and depressive disorder, pharmacists recommended pharmacotherapy adjustments after reviewing the depression treatment history of the patients [23]. Second, pharmacists could conduct medication reviews [27,30,35], sometimes directly at the patients’ home [30]. In a study, family physicians’ office nurses, pharmacists and home care case managers (nurses) collaborated and their processes of care included, at minimum, ahomemedication reviewconductedbya pharmacist [30].

Third, pharmacists supervised the treatment [22,35,40], they discussed alternatives with the physicians [27,37] and in some cases they simplified the dosing regimen or modified the medications [22,24,36]. Leiva et al. described a multifactorial intervention consisting of motivational interviews, pillbox use, family support, blood pressure measurements and simplification of the dosing regimen; pharmacists supervised each patient’s treatment and, whenever possible, simplified the dosing regimen at the follow-up visit [22]. Fourth, pharmacists were in charge of tailoring treatments to patients’ needs [24,35]; in a program for asthmatic patients, pharmacists were responsible for adjusting medications in response to asthma symptoms [24]. Finally, pharmacists guaranteed the access to treatment; for example, they provided written medical justification for use if the prescribed treatment was not the insurance plan’s preferred treatment [27].

3.4.2.2. Information on medications. Pharmacists provided theoretical and practical information on medications, especially during the prescription validation process, with the purpose to ensure patient’s self-management. They educated patients on the proper use of each medication [28] and provided information on the aims, benefits and risks of the treatment [24,36]. Pharmacists informed patients on medication schedules, by anchoring medication to daily life activities (e.g., meal times) [26]. They discussed side effects with patients [24,26,28,29,36,40], drug-drug interactions [36], drug-food interactions [40] and the management of missed doses [36,41]. In an intervention program for patients with pulmonaryarterial hypertension, pharmacists carried out individual interviews and informed patients about the aims, benefits and risks of the treatment, clinical and biological monitoring, drug interactions and management of missed doses and side effects [36].

3.4.2.3. Lifestyle advice. In an intervention, pharmacists gave lifestyle advice. In addition to discussing the importance of taking each of the drugs, the management of the missed doses and the adverse effects, they discussed the importance of diet, exercise and salt intake reduction [26].

3.4.3. Nurses’ areas of expertise Nurses’ areas of expertise focused on 1) patients’ health

assessment and follow-up and 2) patients’ disease education.

3.4.3.1. Patients’ health assessment and follow-up. Nurses were responsible for the specific and delimited clinical activities of patient care. Their range of activities was broad; for example, assessing the cognitivecapacitiesofpatientswithAlzheimeranddementia[35]. Inan intervention for patients with multiple sclerosis [41], nurses were in charge of the pre-treatment medical check-up with theneurologist and the general practitioner; nurses verified that all medical exams were carried out before starting the treatment and they performed blood tests. They monitored the first dose of the medication in collaboration with the neurologist and they were involved in the patient’s follow-up evaluations. In another intervention, nurses were involved in the early detection of adverse effects to medications [32].

1190 J. Celio et al. / Patient Education and Counseling 101 (2018) 1175–1192

3.4.3.2. Patients’ disease education. Nurses educated patients on the disease and corresponding treatments [24,28,33]. In a multidisciplinary intervention for patients with hepatitis C, nurses provided complete and standardized instruction on the disease and the antiviral treatment (i.e., the type of drugs, doses, and administration), while pharmacists reinforced the medication instructions [33]. Nurses explained to patients how to monitor and address symptoms as markers of the severity of the disease. In an intervention for asthmatic patients, nurses explained the use of the peak flow meter to patients [24].

3.5. Communication and information exchange between professionals

Communication and exchange of information between HCPs occurred through team meetings or direct transmission of information (e.g., faxed progress notes [25]), and through the use of the medical patient’s file [29] or diary [32].

Regular HCPs meetings were described in 7 of the 21 identified interventions [23,27,30,32,33,35,36]. Their aim was to discuss patient care and medication-related issues [30,35], or patients’ degree of motivation and adherence [33]. In an intervention, the offsite team (registered nurse depression care manager, clinical pharmacist and psychiatrist) had weekly discussions that occurred in person or via telephone conference; suggestions were successive- ly communicated to the treating clinicians via electronic medical record progress notes [23]. In another intervention, recommenda- tionsissuedbypharmacistswereforwarded tophysiciansandnurses via a report, and discussed collaboratively [36].

In several interventions, the sharing of medication adherence reports was organized through a secured web-platform, which facilitated interprofessional collaborations and long-term moni- toring of outcomes and safety indicators [34,38,41]. Other means for information exchange included the development of a patient diary for treatment follow-up appointments and for recording HCPs’ (pharmacists’, nurses’ and physicians’) information, patient’s comments and a weekly record of drug adverse effects [32].

4. Discussion and conclusion

4.1. Discussion

This review examined 21 references aimed at describing medication adherence-enhancing interventions; the described interventions were conducted by pharmacists and nurses. The literature on the interprofessional collaboration between nurses and pharmacists on medication adherence is limited, which indicates that the importance of these collaborations is not fully elucidated even though both professionals reinforce medication adherence in routine care. Hence, evidence on what constitutes the most effective models of collaborative practice among pharma- cists, nurses, physicians and other health professionals to support and reinforce medication adherence among patients was not identified in our review. However, this review provides valuable insights into better understanding such collaborations in the medical world, where the number of chronic patients increases in parallel to the complexity and costs of treatments, and where medication adherence to chronic treatments has long been neglected. In this review, numerous clinical activities for monitor- ing and supporting medication adherence were described. These observations suggest that medication adherence in the healthcare settings should be included in the prescribing and dispensing procedures and should deserve more attention. Five studies described significant improvements in clinical outcomes [ 23,25,26,30,33], while only four studies showed significant improvements in both medication adherence and clinical out- comes [25,26,30,33]. Among these four studies, three shared two

identical characteristics: strong communication strategies be- tween HCPs and well-defined roles for the pharmacists and nurses [25,30,33]. This corroborates the concept that effective team communication and a clear definition of roles are two of the fundamental prerequisites for effective collaborations among HCPs [11,43], for delivering superior care to patients [44] and better meeting the patients’ needs [45].

Firstly, the lack of a defined role is one of the major limitations in almost all the identified interventions. Secondly, the roles of each professional were only partially described. Thirdly, in most interventions, the responsibilities were assigned to either the pharmacists or nurses but were rarely coordinated, implying that one or the other professional had a marginal role [36].

A decline in responsibilities, a loss of professional identity and interpersonal conflicts are three main risks associated with interdisciplinary and interprofessional collaborations [11]. Phar- macists’ and nurses’ education in medication adherence assess- ment and monitoring during interprofessional trainings could help prevent these common pitfalls [12].

In addition, to ensure the communication of quality among team members and clarity of roles, other factors are important to consider: the team (e.g., a reduced size of the team � between 5 and 10 members, a purposive selection of team members, complementary professional competencies, having strong and democratic team leaders, maturity and flexibility of team members); the relationships (e.g., a good working environment, respect, collaborative attitudes); the objectives (e.g., common goals and shared vision, objectives focused on patient care); the organization (e.g., good balance between individual and collective work, sufficient team meetings); the accessibility (e.g., proximity of team members, e-communication as a supporting platform); institutional support and changes in the workplace (e.g., cultural changes or changes in the reward system can create new opportunities for interprofessional collaborations) [11,43].

The interventions included in our review have limitations related to their designs. The limited number of included patients (n = 5–17) [28,34,40], the lack of randomization [33] and the instruments used to assess adherence [23–25,28–30,39] are the main limitations of these studies. Self-reported adherence ques- tionnaires were often used to monitor adherence, using either validated [24,25,28,30] or not validated [23,29,39] instruments. The adherence-measuring instrument was sometimes not de- scribed [35,36,40,42].

Ten publications did not present any adherence or clinical results [31,32,34–38,40–42]. Moreover, only 12 of the 21 inter- ventions focused primarily on medication adherence (24, 27–29, 31, 34–36, 40–43). For instance, the intervention described by Lelubre et al. is specifically conceived to improve medication adherence [38]. In the other 9 interventions [23,24,28,30,31,35– 37,42], medication adherence is assessed or is part of the intervention but is not the principal outcome. Ultimately, none of the interventions specified which component of medication adherence was addressed, whether initiation, implementation, persistence, or a combination of them.

Finally, 7 interventions were described in conference abstracts [ 31,32,34,41–42]; consequently, the roles of HCPs are only partially or not specified. Additionally, the roles of each professional were poorly described in the original articles. To gain clarity, emphasis should be placed on comprehensive descriptions of the HCPs roles in the literature. This would contribute to a better understanding of new models of care.

4.2. Conclusion

HCPs’ collaborations are already modifying healthcare and long-term patient follow-up. Our review identified the existing

J. Celio et al. / Patient Education and Counseling 101 (2018) 1175–1192 1191

pharmacist-nurse medication adherence-enhancing interventions and described the HCPs’ roles in these interventions.

Our review showed that pharmacists and nurses have common roles, i.e., they screen, assess and support medication adherence, they conduct motivational interviews, they are involved in the patients’ therapeutic education, and they promote self-manage- ment in patients. Aside from these common roles, pharmacists ensure treatment efficacy, security and access; they provide information on medication and related lifestyle advice. Conversely, nurses clinically co-manage patients along with physicians and they provide patients with information on their diseases.

Collaborative pharmacist-nurse medication adherence-enhanc- ing interventions are rare and often at an early developmental stage. More rigorous, high-quality methodological studies focusing on the collaborations of HCPs are needed to provide better support for the impact of these interventions on medication adherence and clinical outcomes. These studies must describe the common and specific roles of HCPs and the establishment of communication flow as focal points. The information collected by each HCP should be systemati- cally shared through effective electronic health records to improve the collaboration and the patient follow-up. Finally, efforts should be pursued in the interprofessional education of HCPs to prepare the new generation of interprofessional clinical teams.

4.3. Practice implications

Our review describes pharmacist-nurse medication adherence- enhancing programs. These results should help in designing new pharmacist-nurse collaborative interventions to improve medica- tion adherence and clinical outcomes. Areas of expertise must be clearly defined and described to take the best advantage of the synergy of interprofessional competencies to answer the chronic patient’s medication adherence needs.

Conflict of interests

The authors declare having no conflict of interest for this review.

Financial support

None.

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