Success of a sustained pharmaceutical care service with electronic adherence monitoring in patient with diabetes over 12 months

We report on the first polypharmacy adherence monitoring over 371 days, integrated into a pharmaceutical care service (counselling, electronic multidrug punch cards, feedback on recent electronic records) for a 65-year-old man with diabetes after hospital discharge. The initial daily regimen of four times per day with 15 pills daily changed after 79 days into a daily regimen of two times per day with 9 pills daily for the next 292 days. The patient removed all medication from the multidrug punch cards (taking adherence 100%) and had 96.9% correct dosing intervals (timing adherence). The 57 evening doses showed the least variation in intake times at 17 h 45 min±8 min. Over the observation year, the patient was clinically stable. He was very satisfied with the multidrug punch card and the feedback on electronic records. In conclusion, long-term monitoring of polypharmacy was associated with the benefit of successful disease management

Early biomarker response and patient preferences to oral and intramuscular vitamin B12 substitution in primary care: a randomised parallel-group trial

Vitamin B12 (VB12) deficiency can be treated with oral high-dose substitution or intramuscular (i.m.) injection of VB12. Whenever alternative routes of administration exist, patient preferences should be considered when choosing the treatment. We aimed to assess outpatient preferences towards oral or IM VB12 substitution and confirm noninferiority of early biomarker response with oral treatment, in a typical primary care population.; Prospective randomised nonblinded parallel-group trial. Patients were recruited by their general practitioner and randomly assigned to oral or IM treatment. Group O-oral was given 28 tablets of 1000 µg cyanocobalamin in a monthly punch card fitted with an electronic monitoring system. Group I-IM received four, weekly injections of 1000 µg hydroxocobalamin. Blood samples were drawn before the first administration and after 1, 2 and 4 weeks of treatment, and analysed for VB12, holotranscobalamin (HoloTc), homocysteine (Hcy) and methylmalonic acid (MMA). For group O-oral, treatment adher-ence and percentage of days with 2 dosing events were calcu-lated. Before and after 28 days of treatment, patients were asked to fill in a questionnaire about their preference for the therapy options and associated factors.; Between November 2013 and December 2015, 37 patients (age: 49.5 ± 18.5 years; women: 60.5%) were recruited for oral (19) or IM (18) treatment. Baseline values with 95% confidence intervals for serum VB12, HoloTc, Hcy and MMA were 158 pmol/l [145-172], 49.0 pmol/l [40.4-57.5], 14.8 µmol/l [12.0-17.7] and 304 nmol/l [219-390], respective-ly, in group O-oral and 164 pmol/l [154-174], 50.1 pmol/l [38.7-61.6], 13.0 µmol/l [11.0-15.1] and 321 nmol/l [215-427], respectively, in group I-IM (not significant). After 1 month of treatment, levels of VB12 and HoloTc showed a significant increase compared with baseline (group O-oral: VB12 354 pmol/l [298-410] and HoloTc 156 pmol/l [116-196]; group I-IM: VB12 2796 pmol/l [1277-4314] and HoloTc 1269 pmol/l [103-2435]). Hcy and MMA levels showed a significant decrease compared with baseline (group O-oral: Hcy 13.8 µmol/l [10.7-16.8] and MMA 168 nmol/l [134-202]; group I-IM: Hcy 8.5 µmol/l [7.1-9.8] and MMA 156 nmol/l [121-190]). HoloTc and MMA levels were normalised in all patients after 4 weeks of treatment, whereas normalisation of VB12 and Hcy was reached by all patients in group I-IM only. Response of VB12, HoloTc and Hcy was more pronounced in group I-IM (p <0.01) and the primary hypothesis that oral VB12 treatment would be noninfe-rior to IM treatment was rejected. Average adherence to thera-py was 99.6 ± 1.1% and days with 2 dosing events reached 5.6%. Before randomisation, preference was in favour of oral treatment (45.9%, n = 17) over IM administration (21.6%, n = 8). Twelve patients (32.4%) had no preference. Nine (24.3%) patients changed their preference after treatment. Patients who obtained their preferred route of administration main-tained their preference in the case of oral treatment and changed their preference after IM treatment.; Differences in VB12 levels between groups were higher than expected. Therefore, noninferiority of oral treat-ment had to be rejected. However, normalisation of HoloTc and MMA was reached by all patients after a 1-month treatment period. The clinical benefit of the exaggerated biomarker re-sponse after IM treatment within a typical primary care popula-tion is questionable. Midterm biomarker effects and patient preferences should be considered when a therapeutic scheme is chosen. Initial rating in favour of either IM or oral therapy can change over time and justifies repeated re-evaluation of patient preferences. (ClinicalTrials.gov ID NCT01832129)

Novel Medication Supply Model Guarantees Adequate Management and High Adherence to Polypharmacy in Older Opioid Users – Preliminary Results with Outpatients

Background: Life expectancy of older drug users has increased, primarily thanks to opioid agonist treatment (OAT). Nursing homes are often not adapted to accommodate patients with substance use disorders. Although care and adherence to polypharmacy in older opioid users need considerable resources e.g., daily visits to an outpatient clinic, outpatient treatment and surveillance are provided as long as possible. We developed a novel medication supply model with an electronic dispenser of pre-packed medications located at patient home, after allowing for law requirements concerning the dispensing of opioids, and present preliminary results from three illustrative outpatients. Methods: The community pharmacy provided unit-of-dose pouches with all solid oral medications directly to patient home. Opioids for substitution were obtained at the addiction clinic in at least weekly intervals, otherwise in the pouches. The pouches were loaded into a lockable, remote-controlled medication management aid that was programmed according to the patient’s medication schedule. The dispenser reminds patients with acoustic alerts to take their medication and records dates and times of medication retrievals. It automatically sends an alert if a patient misses to retrieve a dose. Results: Our three outpatients used the electronic dispenser during 659, 118 and 61 days, with a total of 5, 9, and 18 pills to take daily at 1, 3 and 5 intake times, respectively. The majority of the doses were taken on the preset time (94%, 68.2% and 73.7%) or deliberately in advance (pocket dose). Clinical benefits were initiation and maintenance of a therapy for dementia over 18 months and suppression of HIV viral load over 1.8 years (patient 1), prevention of further dose escalation of pain medication (patient 2) and release of prompts to initiate the existential task of cooking (patient 3). Conclusion: Our novel supply model allows adequate implementation and persistence of complex treatments with outpatients. Clinical outcomes improved, patients and caregivers were satisfied, and resources were saved

Inconclusiveness of psychometric testing of medication adherence questionnaires

Purpose To propose a paradigm change for the validation procedures of medication adherence questionnaires. Methods A total of 121 validation procedures of unique questionnaires for medication adherence were analyzed. Results “Construct validity” and “internal consistency” were most often assessed, and test results varied largely. A more in-depth analysis indicated that the assessment of medication non-adherence included distinct but related constructs, such as the extent to which doses are missed, and the attempt to identify different facets of medication-taking behavior. Consequently, each construct requires a different measurement approach with different psychometric tests for establishing its validity and reliability. Conclusion Results show that assessing the validity and reliability of adherence questionnaires with standard procedures including statistical tests is inconclusive. Refinement of the constructs of non-adherence is needed in pharmacy and medical practice. We suggest a distinction between the (i) extent of missed doses over the past 2 weeks, (ii) modifiable reasons for non-adherence behavior, and (iii) unmodifiable factors of non-adherence. Validation procedures and corresponding statistical methods should be selected according to the specific single constructs

A Systematic Review of Medication Adherence Thresholds Dependent of Clinical Outcomes

Background: In pharmacotherapy, the achievement of a target clinical outcome requires a certain level of medication intake or adherence. Based on Haynes's early empirical definition of sufficient adherence to antihypertensive medications as taking ≥80% of medication, many researchers used this threshold to distinguish adherent from non-adherent patients. However, we propose that different diseases, medications and patient's characteristics influence the cut-off point of the adherence rate above which the clinical outcome is satisfactory (thereafter medication adherence threshold). Moreover, the assessment of adherence and clinical outcomes may differ greatly and should be taken into consideration. To our knowledge, very few studies have defined adherence rates linked to clinical outcomes. We aimed at investigating medication adherence thresholds in relation to clinical outcomes.Method: We searched for studies that determined the relationship between adherence rates and clinical outcomes in the databases PubMed, EmbaseⓇ and Web of Science™ until December 2017, limited to English-language. Our outcome measure was any threshold value of adherence. The inclusion criteria of the retrieved studies were (1) any measurement of medication adherence, (2) any assessment of clinical outcomes, and (3) any method to define medication adherence thresholds in relation to clinical outcomes. We excluded articles considered as a tutorial. Two authors (PB and IA) independently screened titles and abstracts for relevance, reviewed full-texts, and extracted items. The results of the included studies are presented qualitatively.Result: We analyzed 6 articles that assessed clinical outcomes linked to adherence rates in 7 chronic disease states. Medication adherence was measured with Medication Possession Ratio (MPR, n = 3), Proportion of Days Covered (PDC, n = 1), both (n = 1), or Medication Event Monitoring System (MEMS). Clinical outcomes were event free episodes, hospitalization, cortisone use, reported symptoms and reduction of lipid levels. To find the relationship between the targeted clinical outcome and adherence rates, three studies applied logistic regression and three used survival analysis. Five studies defined adherence thresholds between 46 and 92%. One study confirmed the 80% threshold as valid to distinguish adherent from non-adherent patients.Conclusion: The analyzed studies were highly heterogeneous, predominantly concerning methods of calculating adherence. We could not compare studies quantitatively, mostly because adherence rates could not be standardized. Therefore, we cannot reject or confirm the validity of the historical 80% threshold. Nevertheless, the 80% threshold was clearly questioned as a general standard

Development and validation of the 15-STARS - A novel self-report pharmacy-based questionnaire to screen for medication non-adherence

Background Published scales measuring medication adherence are myriad. There is a need for a tool that guides towards downstream adherence interventions. Objective To develop and validate a self-report questionnaire able to detect modifiable determinants of medication non-adherence. Methods Workshops, surveys and meetings were used to identify items. Validation was performed in French and German (Switzerland) between March and April 2022. Face validation, content validation, construct validation, internal consistency and test-retest reliability were assessed. The questionnaire was finalized in August 2022. Results The first draft in English included 13 items divided into four areas. Following translation, validation was performed with 144 patients (63 German-, 81 French-speaking) who were recruited in 35 community pharmacies. Acceptability was good (<5% missing data). Psychometric properties were acceptable with good content validity and moderate construct validity. Internal consistency was acceptable for the French version (Cronbach’s alpha = 0.71 [item 1–5] - 0.61 [item 6–9]) and less acceptable for the German version (Cronbach’s alpha = 0.43 [item 1–5] - 0.45 [item 6–9]). Test-retest was given for all items (r = 0.52 to 1.0) except item 10 in French (r = 0.25). The final instrument is a 15-item questionnaire called the 15-STARS (Screening Tool for AdheRence to medicineS) that assesses practical difficulties with medicine use, reasons for non-adherence, doses missed, and need for further help. Conclusions Our findings support the validity and clinical utility of the 15-STARS questionnaire. Reliability was inconclusive due to incoherent internal consistency, but explainable by the single-item nature of the scale. This new tool will enable the detection of patients who experience difficulties that negatively influence medication adherence. Pharmacists will be able to propose specific and tailored adherence interventions to the patients. Next steps will focus on evaluating its usefulness for developing targeted interventions that optimize medication adherence in routine care and research settings

Matching Adherence Interventions to Patient Determinants Using the Theoretical Domains Framework

Introduction: Despite much research, interventions to improve medication adherence report disappointing and inconsistent results. Tailored approaches that match interventions and patient determinants of non-adherence were seldom used in clinical trials. The presence of a multitude of theoretical frameworks and models to categorize interventions and patient determinants complicated the development of common categories shared by interventions and determinants. We retrieved potential interventions and patient determinants from published literature on medication adherence, matched them like locks and keys, and categorized them according to the Theoretical Domains Framework (TDF). Methods: We identified the most relevant literature reviews on interventions and determinants in a pragmatic literature search, extracted all interventions and determinants, grouped similar concepts to umbrella terms and assigned them to TDF categories. All steps were finalized in consensus discussion between the authors. Results: Sixteen articles (5 with determinants, 11 with interventions) were included for analysis. We extracted 103 interventions and 42 determinants that we divided in 26 modifiable and 16 unmodifiable determinants. All interventions and modifiable determinants were matched within 11 categories (Knowledge; Skills; Social/professional role and identity; Beliefs about capabilities; Beliefs about consequences; Intentions; Memory, Attention and decision processes; Environmental context and resources; Social influences; Emotion; and Behavioral regulation). Conclusion: In published trials on medication adherence, the congruence between interventions and determinants can be assessed with matching interventions to determinants. To be successful, interventions in medication adherence should target current modifiable determinants and be tailored to the unmodifiable determinants. Modifiable and unmodifiable determinants need to be assessed at inclusion of intervention studies to identify the patients most in need of an adherence intervention. Our matched categories may be useful to develop interventions in trials that investigate the effectiveness of adherence interventions

Proposal of standardization to assess adherence with medication records: methodology matters

Medication adherence is the process by which patients take their medication as prescribed and is an umbrella term that encompasses all aspects of medication use patterns. Ambiguous terminology has emerged to describe a deviation from prescribed regimen, forcing the European ABC Project to define 3 phases of medication use: initiation, implementation, and discontinuation. However, different measures of medication adherence using medication records are currently available that do not always distinguish between these phases. The literature is lacking standardization and operationalization of the assessment methods.; To propose a harmonization of standards as well as definitions of distinct measures and their operationalization to quantify adherence to medication from medication records.; Group discussions and consensus process among all coauthors. The propositions were generated using the authors' experiences and views in the field of adherence, informed by theory.; The concepts of adherence measures within the new taxonomy were harmonized, and the standards necessary for the operationalization of adherence measures from medication records are proposed. Besides percentages and time-to values, the addition of a dichotomous value for the reinitiation of treatment is proposed. Methodological issues are listed that should be disclosed in studies on adherence.; The possible impact of the measures in adherence research is discussed. By doing this, the results of future adherence research should gain in accuracy. Finally, studies will become more transparent, enabling comparison between studies

Protocol for MAAESTRO: Electronic Monitoring and Improvement of Adherence to Direct Oral Anticoagulant Treatment—A Randomized Crossover Study of an Educational and Reminder-Based Intervention in Ischemic STROke Patients Under Polypharmacy

Background: Non-adherence to direct oral anticoagulants (DOACs) remains a matter of concern, especially for patients with a recent stroke. However, data on electronically monitored adherence and adherence-improving interventions are scarce.Aims: We aim to use electronic monitoring in DOAC-treated stroke patients to (i) evaluate the effect of an educational, reminder-based adherence-improving intervention, (ii) investigate predictors of non-adherence, (iii) identify reliable self-report measures of adherence, and (iv) explore the association of non-adherence with clinical outcomes.Methods: Single-center, randomized, crossover, open-label study. Adherence to DOACs of polymedicated patients self-administering their medication will be monitored electronically throughout the 12-month-long study following hospitalization for ischemic stroke. After a 6-month observational phase, patients will receive pharmaceutical counseling with feedback on their intake history and be given a multi-compartment pillbox for the subsequent 6-month interventional phase. The pillbox will provide intake reminders either during the first or the last three interventional-phase months. Patients will be randomly allocated to reminders-first or reminders-last.Study outcomes: Primary: non-optimal timing adherence; Secondary: non-optimal taking adherence; timing adherence; taking adherence; self-reported adherence; clinical outcomes including ischemic and hemorrhagic events; patient-reported device usability and satisfaction.Sample size estimates: A sample of 130 patients provides 90% power to show a 20% improvement of the primary adherence outcome with intake reminders.Discussion: MAAESTRO will investigate various aspects of non-adherence and evaluate the effect of an adherence-improving intervention in DOAC-treated patients with a recent stroke using electronic monitoring.Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03344146, Swiss National Clinical Trials Portal SNCTP00000241