The differential impact of a 6-versus 12-month pharmacist-led interprofessional medication adherence program on medication adherence in patients with diabetic kidney disease: the randomized PANDIA-IRIS study.

Background: For every 100 patients with diabetes, 40 will develop diabetic kidney disease (DKD) over time. This diabetes complication may be partly due to poor adherence to their prescribed medications. In this study, we aimed to evaluate the differential impact of a 6- versus 12-month pharmacist-led interprofessional medication adherence program (IMAP) on the components of adherence (i.e., implementation and discontinuation) in patients with DKD, during and after the intervention. Methods: All included patients benefited from the IMAP, which consists in face-to-face regular motivational interviews between the patient and the pharmacist based on the adherence feedback from electronic monitors (EMs), in which the prescribed treatments were delivered. Adherence reports were available to prescribers during the intervention period. Patients were randomized 1:1 into two parallel arms: a 12-month IMAP intervention in group A versus a 6-month intervention in group B. Adherence was monitored continuously for 24 months post-inclusion during the consecutive intervention and follow-up phases. In the follow-up phase post-intervention, EM data were blinded. Blood pressure was measured by the pharmacist at each visit. The repeated measures of daily patient medication intake outcomes (1/0) to antidiabetics, antihypertensive drugs, and statins were modeled longitudinally using the generalized estimated equation in both groups and in both the intervention and the follow-up phases. Results: EM data of 72 patients were analyzed (34 in group A and 38 in group B). Patient implementation to antidiabetics and antihypertensive drugs increased during the IMAP intervention phase and decreased progressively during the follow-up period. At 12 months, implementation to antidiabetics was statistically higher in group A versus group B (93.8% versus 86.8%; Δ 7.0%, 95% CI: 5.7%; 8.3%); implementation to antihypertensive drugs was also higher in group A versus B (97.9% versus 92.1%; Δ 5.8%, 95% CI: 4.8%; 6.7%). At 24 months, implementation to antidiabetics and antihypertensive drugs remained higher in group A versus B (for antidiabetics: 88.6% versus 85.6%; Δ 3.0%, 95% CI: 1.7%; 4.4% and for antihypertensive drugs: 94.4% versus 85.9%; Δ 8.5%, 95% CI: 6.6%; 10.7%). No difference in pharmacy-based blood pressure was observed between groups. Implementation to statins was comparable at each time point between groups. Three patients discontinued at least one treatment; they were all in group B. In total, 46% (16/35) of patients in the 12-month intervention versus 37% (14/38) of patients in the 6-month intervention left the study during the intervention phase, mainly due to personal reasons. Conclusion: The IMAP improves adherence to chronic medications in patients with DKD. The longer the patients benefit from the intervention, the more the implementation increases over time, and the more the effect lasts after the end of the intervention. These data suggest that a 12-month rather than a 6-month program should be provided as a standard of care to support medication adherence in this population. The impact on clinical outcomes needs to be demonstrated. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04190251_PANDIA IRIS.

[Diabetic nephropathy: Interprofessional support of medication adherence]. / Néphropathie diabétique : soutenir l'adhésion médicamenteuse de façon interprofessionnelle.

Medication non-adherence in patients with diabetic kidney disease (DKD) is endemic. The PANDIA-IRIS study, implemented at the community pharmacy of Unisanté, illustrates the support of medication adherence in patients with DKD by pharmacists, through an interprofessional program (IMAP) based on a behavioral science theoretical framework. Implementing behavioural support programmes such as PANDIA-IRIS on a large scale in Switzerland is both a necessity and a challenge. These programmes should be an integral part of standard patient care. The transition of care towards interprofessional collaborations and a clarification of roles in supporting adherence, including the patient as a partner, will contribute to fully considering adherence in therapeutic decision making and support to enable better achievement of long-term clinical goals.

La non-adhésion médicamenteuse chez les patient-es avec une néphropathie diabétique (ND) est endémique. L'étude PANDIA-IRIS, implémentée à la pharmacie communautaire d'Unisanté, illustre le soutien de l'adhésion des patient-es avec ND par des pharmacien-nes, au travers d'un programme interprofessionnel (IMAP) fondé sur un cadre théorique des sciences du comportement. Mettre en place des programmes d'accompagnement comportemental comme PANDIA-IRIS à large échelle en Suisse est à la fois une nécessité et un défi. Ces programmes devraient faire partie intégrante des soins standards des patient-es. La transition des soins vers des collaborations interprofessionnelles et une clarification des rôles dans le soutien de l'adhésion, incluant le-la patient-e comme partenaire, contribueront à considérer pleinement l'adhésion dans la prise de décisions thérapeutiques et dans son accompagnement pour permettre une meilleure atteinte des objectifs cliniques à long terme.

Adherence to the CDK 4/6 Inhibitor Palbociclib and Omission of Dose Management Supported by Pharmacometric Modelling as Part of the OpTAT Study.

The cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib is administered orally and cyclically, causing medication adherence challenges. We evaluated components of adherence to palbociclib, its relationship with pharmacokinetics (PK), and drug-induced neutropenia. Patients with metastatic breast cancer (MBC) receiving palbociclib, delivered in electronic monitors (EM), were randomized 1:1 to an intervention and a control group. The intervention was a 12-month interprofessional medication adherence program (IMAP) along with monthly motivational interviews by a pharmacist. Implementation adherence was compared between groups using generalized estimating equation models, in which covariates were included. Model-based palbociclib PK and neutrophil profiles were simulated under real-life implementation scenarios: (1) optimal, (2) 2 doses omitted and caught up at cycle end. At 6 months, implementation was slightly higher and more stable in the intervention (n = 19) than in the control (n = 19) group, 99.2% and 97.3% (Δ1.95%, 95% CI 1.1−2.9%), respectively. The impact of the intervention was larger in patients diagnosed with MBC for >2 years (Δ3.6%, 95% CI 2.1−5.4%), patients who received >4 cycles before inclusion (Δ3.1%, 95% CI 1.7−4.8%) and patients >65 (Δ2.3%, 95% CI 0.8−3.6%). Simulations showed that 25% of patients had neutropenia grade ≥3 during the next cycle in scenario 1 versus 30% in scenario 2. Education and monitoring of patient CDK4/6i cycle management and adherence along with therapeutic drug monitoring can help clinicians improve prescription and decrease toxicity.

Medication Adherence Evaluated Through Electronic Monitors During the 2020 COVID-19 Pandemic Lockdown in Switzerland: A Longitudinal Analysis.

Background: During the 2020 COVID-19 lockdown, patients included in the Interprofessional Medication Adherence Program (IMAP) in Switzerland continued to use electronic monitors (EMs) that registered daily drug-dose intake. We aimed to understand to what extent patients' medication implementation (ie, the extent to which the patient took the prescribed medicine), measured with EMs, was impacted by the lockdown. Methods: Patients participating in the IMAP were diagnosed with diabetic kidney disease (DKD), solid cancer, human immunodeficiency virus (HIV) and miscellaneous long-term diseases (MLTD). Patient implementation was defined through a proxy: if all patient EMs were opened at least once daily, implementation was considered active (=1), and no implementation was considered (=0) otherwise. Implementation before (from December 2019 to March 2020), during (March to June 2020) and after (June to September 2020) the lockdown was compared. Subanalyses were performed according to the patients' diseases. Subanalyses were performed in patients who used at least one EM in 2018-2019 during the same periods (defined as winter, spring and summer). The logistic regression models used to estimate medication implementation according to the period were fitted using generalized estimating equations. Results: In 2020, patient implementation (n = 118) did not differ significantly before versus during (OR = 0.98, 95% CI: 0.84-1.15, p = 0.789) and before versus after (OR = 0.91, 95% CI: 0.79-1.06, p = 0.217) the lockdown. These findings remained stable when separately analyzing the implementation of patients with HIV (n = 61), DKD (n = 25) or MLTD (n = 22). Too few patients with cancer were included (n = 10) to interpret the results. In 2019, the implementation of 61/118 (51.7%) patients was significantly lower during summertime versus wintertime (OR = 0.73, 95% CI: 0.60-0.89, p = 0.002). Conclusion: Medication implementation remained steady before, during and after the lockdown in 2020. The IMAP before, during and after the lockdown may have supported the adherence of most patients, by ensuring continuity of care during periods of routine disturbances.

Understanding reasons and factors for participation and non-participation to a medication adherence program for patients with diabetic kidney disease in Switzerland: a mixed methods study.

BACKGROUND: An interprofessional medication adherence intervention led by pharmacists, combining motivational interviews and feedback with electronic monitor (EM) drug assessment, was offered to all consecutive patients with diabetic kidney disease (DKD) (estimated glomerular filtration rate < 60 mL/min/1.73 m2) visiting their nephrologist or endocrinologist. Approximately 73% (202/275) of eligible patients declined to participate, and the factors and reasons for refusal were investigated. METHODS: Sociodemographic and clinical data of included patients and those who refused were collected retrospectively for those who had previously signed the general consent form. Multivariate logistic regression analysis was performed to identify independent variables associated with non-participation. Patients who refused or accepted the adherence study were invited to participate in semi-structured interviews. Verbatim transcription, thematic analysis, and inductive coding were performed. RESULTS: Patients who refused to participate were older (n = 123, mean age 67.7 years, SD:10.4) than those who accepted (n = 57, mean age 64.0 years, SD:10.0, p = 0.027) and the proportion of women was higher among them than among patients who accepted it (30.9% vs 12.3%, p = 0.007). The time from diabetes diagnosis was longer in patients who refused than in those who accepted (median 14.2 years IQR 6.9-22.7 vs. 8.6 years, IQR 4.5-15.9, p = 0.003). Factors associated with an increased risk of non-participation were female sex (OR 3.8, 95% CI 1.4-10.0, p = 0.007) and the time from diabetes diagnosis (OR 1.05, 95% CI 1.01-1.09, p = 0.019). The included patients who were interviewed (n = 14) found the interprofessional intervention useful to improve their medication management, support medication literacy, and motivation. Patients who refused to participate and who were interviewed (n = 16) explained no perceived need, did not agree to use EM, and perceived the study as a burden and shared that the study would have been beneficial if introduced earlier in their therapeutic journey. Other barriers emerged as difficult relationships with healthcare providers, lack of awareness of the pharmacist's role, and negative perception of clinical research. CONCLUSIONS: Investigating the factors and reasons for participation and non-participation in a study helps tailor intervention designs to the needs of polypharmacy patients. Patients who refused the adherence intervention may not be aware of the benefits of medication management and medication literacy. There is an urgent need to advocate for interprofessional outpatient collaborations to support medication adherence in patients with DKD. Trial registration Clinicaltrials.gov NCT04190251_PANDIA IRIS.

Response to the first wave of the COVID-19 pandemic in the community pharmacy of a University Center for Primary Care and Public Health.

BACKGROUND: Pharmacists played a key role during the coronavirus disease 2019 (COVID-19) pandemic: they contributed to preventing transmission and to maintaining continuity of primary care. OBJECTIVES: To present the contributions of a Swiss pharmacy of an academic outpatient care department (Unisanté) to the prevention of COVID-19 transmission and the precautionary measures plan implemented as well as to evaluate the impact of Swiss semicontainment on its pharmacy services. METHODS: Contributions to COVID-19 transmission prevention and the precautionary measures plan are described. The impact on pharmacy services was measured by quantitative comparison before, during and after semicontainment. RESULTS: The pharmacy supplied protective equipment to the population and to liberal healthcare professionals and provided COVID-19 recommendations to patients and community pharmacies. The precautionary measures plan implemented required a reorganization of the premises, facilities, staff operation and pharmacy services. Semicontainment had a strong impact on pharmacy services; however, clinical bonds with patients and other healthcare professionals were maintained. Unseen negative impacts may exist and need to be investigated. CONCLUSIONS: Although innovative solutions remain to be developed to guarantee continuous and secure remote communication with patients, this pandemic was an opportunity to demonstrate the versatility, benefit and importance of community pharmacy services.

Optimizing Oral Targeted Anticancer Therapies Study for Patients With Solid Cancer: Protocol for a Randomized Controlled Medication Adherence Program Along With Systematic Collection and Modeling of Pharmacokinetic and Pharmacodynamic Data.

BACKGROUND: The strengthening or substitution of intravenous cytotoxic chemotherapy cycles by oral targeted anticancer therapies, such as protein kinase inhibitors (PKIs), has provided impressive clinical benefits and autonomy as well as a better quality of life for patients with cancer. Despite these advances, adverse event management at home and medication adherence remain challenging. In addition, PKI plasma concentrations vary significantly among patients with cancer receiving the same dosage, which could explain part of the observed variability in the therapeutic response. OBJECTIVE: The aim of this optimizing oral targeted anticancer therapies (OpTAT) study is to optimize and individualize targeted anticancer treatments to improve patient care and self-monitoring through an interprofessional medication adherence program (IMAP) combined with measurement PKI plasma concentrations. METHODS: The OpTAT study has two parts: (1) a 1:1 randomized medication adherence program, in which the intervention consists of regular motivational interviewing sessions between the patient and the pharmacist, along with the delivery of PKIs in electronic monitors, and (2) a systematic collection of blood samples and clinical and biological data for combined pharmacokinetic and pharmacodynamic analysis. On the basis of the electronic monitor data, medication adherence will be compared between groups following the three operational definitions: implementation of treatment during the persistent period, persistence with treatment and longitudinal adherence. The implementation will be described using generalized estimating equation models. The persistence of PKI use will be represented using a Kaplan-Meier survival curve. Longitudinal adherence is defined as the product of persistence and implementation. PKI pharmacokinetics will be studied using a population approach. The relationship between drug exposure and efficacy outcomes will be explored using Cox regression analysis of progression-free survival. The relationship between drug exposure and toxicity will be analyzed using a pharmacokinetic-pharmacodynamic model and by logistic regression analysis. Receiver operating characteristic analyses will be applied to evaluate the best exposure threshold associated with clinical benefits. RESULTS: The first patient was included in May 2015. As of June 2021, 262 patients had participated in at least one part of the study: 250 patients gave at least one blood sample, and 130 participated in the adherence study. Data collection is in process, and the final data analysis is planned to be performed in 2022. CONCLUSIONS: The OpTAT study will inform us about the effectiveness of the IMAP program in patients with solid cancers treated with PKIs. It will also shed light on PKI pharmacokinetic and pharmacodynamic properties, with the aim of learning how to adapt the PKI dosage at the individual patient level to increase PKI clinical suitability. The IMAP program will enable interprofessional teams to learn about patients' needs and to consider their concerns about their PKI self-management, considering the patient as an active partner. TRIAL REGISTRATION: ClinicalTrials.gov NCT04484064; https://clinicaltrials.gov/ct2/show/NCT04484064. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30090.

Interprofessional Medication Adherence Program for Patients With Diabetic Kidney Disease: Protocol for a Randomized Controlled and Qualitative Study (PANDIA-IRIS).

BACKGROUND: Despite effective treatments, more than 30% of patients with diabetes will present with diabetic kidney disease (DKD) at some point. Patients with DKD are among the most complex as their care is multifactorial and involves different groups of health care providers. Suboptimal adherence to polypharmacy is frequent and contributes to poor outcomes. As self-management is one of the keys to clinical success, structured medication adherence programs are crucial. The PANDIA-IRIS (patients diabétiques et insuffisants rénaux: un programme interdisciplinaire de soutien à l'adhésion thérapeutique) study is based on a routine medication adherence program led by pharmacists. OBJECTIVE: The aim of this study is to define the impact of the duration of this medication adherence program on long-term adherence and clinical outcomes in patients with DKD. METHODS: This monocentric adherence program consists of short, repeated motivational interviews focused on patients' medication behaviors combined with the use of electronic monitors containing patients' medications. When patients open the electronic monitor cap to take their medication, the date and hour at each opening are registered. In total, 73 patients are randomized as 1:1 in 2 parallel groups; the adherence program will last 6 months in the first group versus 12 months in the second group. After the intervention phases, patients continue using their electronic monitors for a total of 24 months but without receiving feedback. Electronic monitors and pill counts are used to assess medication adherence. Persistence and implementation will be described using Kaplan-Meier curves and generalized estimating equation multimodeling, respectively. Longitudinal adherence will be presented as the product of persistence and implementation and modelized by generalized estimating equation multimodeling. The evolution of the ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron Modified-Release Controlled Evaluation) and UKPDS (United Kingdom Prospective Diabetes Study) clinical scores based on medication adherence will be analyzed with generalized estimating equation multimodeling. Patients' satisfaction with this study will be assessed through qualitative interviews, which will be transcribed verbatim, coded, and analyzed for the main themes. RESULTS: This study was approved by the local ethics committee (Vaud, Switzerland) in November 2015. Since then, 2 amendments to the protocol have been approved in June 2017 and October 2019. Patients' recruitment began in April 2016 and ended in October 2020. This study was introduced to all consecutive eligible patients (n=275). Among them, 73 accepted to participate (26.5%) and 202 (73.5%) refused. Data collection is ongoing and data analysis is planned for 2022. CONCLUSIONS: The PANDIA-IRIS study will provide crucial information about the impact of the medication adherence program on the adherence and clinical outcomes of patients with DKD. Monitoring medication adherence during the postintervention phase is innovative and will shed light on the duration of the intervention on medication adherence. TRIAL REGISTRATION: Clinicaltrials.gov NCT04190251_PANDIA IRIS; https://clinicaltrials.gov/ct2/show/NCT04190251. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25966.

[Medication adherence and physician-pharmacist collaboration. Focus on the patient with diabetic nephropathy]. / Adhésion thérapeutique et collaboration médecin-pharmacien. L'exemple du patient avec néphropathie diabétique.

Polypharmacy is common in patients with a chronic disease. It is appropriate when both the patient and the physician discuss the goal of each prescribed medication with a motivated patient capable of managing his/her medication. It can however be inappropriate when treatment becomes too complex for the frail patient. The risk is non-adherence to therapy, which often results in an intensification of treatment due to unmet therapeutic goals. Collaboration between physicians and pharmacists is therefore essential for the educational support of patients with polypharmacy. In this article, we review the studies examining the impact of a physician-pharmacist collaboration on the medication adherence of diabetic patients with renal impairment.

La polypharmacie concerne de nombreux patients avec une maladie chronique. Elle est appropriée lorsque chaque médicament a été prescrit dans un but thérapeutique spécifique discuté avec un patient motivé et capable de gérer ses médicaments. Elle peut cependant être inappropriée lorsque le traitement devient trop complexe pour une personne fragile. Le risque est une non-adhésion au traitement, dont découle souvent une intensification de la thérapie en raison d'objectifs thérapeutiques non atteints. La collaboration médecin-pharmacien est donc primordiale pour l'accompagnement éducatif du patient complexe dans la gestion de ses médicaments. Dans cet article, nous revoyons les études examinant l'adhésion thérapeutique chez le patient diabétique avec une atteinte rénale lors d'une collaboration médecin-pharmacien.

Patient adherence to rivaroxaban in deep vein thrombosis, a cohort study in Switzerland: quantitative results.

Background Direct oral anticoagulants (DOACs) have the advantage of being administered orally at a fixed dose without laboratory monitoring, in contrast to the frequent international normalized ratio measurements used to adjust for vitamin K antagonists dosing. Rivaroxaban, has a short half-life. The anticoagulation effect rapidly decreases if medication adherence is suboptimal. Objective The purpose of this quantitative study (called RIVA) is to longitudinally describe adherence to rivaroxaban (implementation and persistence) in patients with deep vein thrombosis (DVT). Setting The community pharmacy of the Center for Primary Care and Public Health (Unisanté), University of Lausanne, Switzerland in collaboration with the angiology division of the Lausanne University Hospital (CHUV). Methods This is an observational study. Patients received rivaroxaban for 3 or 6 months: 15 mg twice a day during the first 3 weeks and then 20 mg once a day until the end of the treatment. Adherence was measured using electronic monitoring. Implementation and adherence were modelled using a generalized estimating equation model. Persistence was represented using a Kaplan-Meier survival curve. Main outcome measure Medication adherence (implementation and persistence). Results Thirty-one consecutive patients were included (68% male, mean age: 47 years old). The collected adherence data consisted of 57 inter-visit phases, 2899 electronic monitoring openings and a median follow-up of 92 days (IQR: 87; 100). Implementation to rivaroxaban was initially high [96.3 (92.8; 98.1)] but decreased during the first 3 weeks, until it reached 89.3 (76.0; 95.6). After the switch from twice a day 15 mg to a once a day 20 mg regimen, implementation increased again and remained stable [95.4 (92.2; 97.3)] for 90 days. Four patients who experienced adverse events discontinued the treatment before the end of the study and were considered non-persistent (clinically appropriate discontinuation). Conclusion Adherence to rivaroxaban in deep vein trombosis is high in persistent patients. Discontinuation is related to rivaroxaban adverse effects/toxicity. Implementation should be reinforced during the twice a day-phase, and this first 3-week experience should help patients and healthcare professionals choose the best timing for the once a day phase.