Examining assumptions regarding valid electronic monitoring of medication therapy: development of a validation framework and its application on a European sample of kidney transplant patients

BACKGROUND: Electronic monitoring (EM) is used increasingly to measure medication non-adherence. Unbiased EM assessment requires fulfillment of assumptions. The purpose of this study was to determine assumptions needed for internal and external validity of EM measurement. To test internal validity, we examined if (1) EM equipment functioned correctly, (2) if all EM bottle openings corresponded to actual drug intake, and (3) if EM did not influence a patient's normal adherence behavior. To assess external validity, we examined if there were indications that using EM affected the sample representativeness. METHODS: We used data from the Supporting Medication Adherence in Renal Transplantation (SMART) study, which included 250 adult renal transplant patients whose adherence to immunosuppressive drugs was measured during 3 months with the Medication Event Monitoring System (MEMS). Internal validity was determined by assessing the prevalence of nonfunctioning EM systems, the prevalence of patient-reported discrepancies between cap openings and actual intakes (using contemporaneous notes and interview at the end of the study), and by exploring whether adherence was initially uncharacteristically high and decreased over time (an indication of a possible EM intervention effect). Sample representativeness was examined by screening for differences between participants and non-participants or drop outs on non-adherence. RESULTS: Our analysis revealed that some assumptions were not fulfilled: 1) one cap malfunctioned (0.4%), 2) self-reported mismatches between bottle openings and actual drug intake occurred in 62% of the patients (n = 155), and 3) adherence decreased over the first 5 weeks of the monitoring, indicating that EM had a waning intervention effect. CONCLUSION: The validity assumptions presented in this article should be checked in future studies using EM as a measure of medication non-adherence

Evaluation of medication adherence methods in the treatment of malaria in Rwandan infants

Objectives: To compare three methods for evaluating treatment adherence in a 7-day controlled treatment period for malaria in children in Rwanda. Methods: Fifty-six children (< 5 years) with malaria were recruited at the University Hospital of Butare, Rwanda. Patients were treated with quinine sulfate, taste-masked, pellets during seven days: three days in hospital (in-patient) followed by a four-day out-patient period. Three methods to evaluate medication adherence among patients were compared: manual pill count of returned tablets, patient self-report and electronic pill-box monitoring. These pill-boxes were equipped with a microchip registering date and time of every opening. Medication adherence was defined as the proportion of prescribed doses taken. The inter-dose intervals were analysed as well. Results: Medication adherence data were available for 54 of the 56 patients. Manual pill count and patient self-report yielded a medication adherence of 100% for the in-and out-patient treatment periods. Based on electronic pill-box monitoring, medication adherence during the seven-day treatment period was 90.5 +/- 8.3%. Based on electronic pillbox monitoring inpatient medication adherence (99.3 +/- 2.7%) was markedly higher (p < 0.03) than out-patient adherence (82.7 +/- 14.7%), showing a clear difference between health workers' and consumers' medication adherence. Conclusion: Health workers' medication adherence was good. However, a significant lower medication adherence was observed for consumers' adherence in the outpatient setting. This was only detected by electronic pill-box monitoring. Therefore, this latter method is more accurate than the two other methods used in this study

Effectiveness and Content Analysis of Interventions to Enhance Oral Antidiabetic Drug Adherence in Adults with Type 2 Diabetes : Systematic Review and Meta-Analysis

We thank Frederic Bergeron, information scientist, for assistance in search strategies. We thank American Journal Experts for editing the text. Source of financial support: This study was funded by the Laval University Chair on Adherence to Treatments. This Chair is supported by nonrestricted grants from AstraZeneca Canada, Merck Canada, Sanofi Canada, and Pfizer Canada and from the Prends soin de toi program (a Quebec provincial program for the improvement of public health).Peer reviewedPostprin

Adherence to self-administered tuberculosis treatment in a high HIV-prevalence setting: a cross-sectional survey in Homa Bay, Kenya.

Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools

Adherence to Highly Active Antiretroviral Therapy (HAART) in HIV/AIDS Patient

HIV infection has been considered as a chronic illness since the availability of highly active anti retroviral treatments (HAART). The introduction of HAART to HIV/AIDS patient improve quality of life, life expectancy, decrease rate of resistance and further decrease mortality to AIDS related causes. Many studies showed the evidence of HAART efficacy to suppress viral replication among patient with continuum adherence to treatment. However, unlike other chronic medications which were only needed at least 70% adherence; success virological suppression rate in HIV/AIDS in patient required as high as 95% or near perfect adherence; and this remains to be an important issue for patient on HAART.In term of treatment, a long-term follow up of patient’s adherence, i.e. daily medication intake monitoring for life, becomes a routine practice. However, no gold standard is established to measure patients’ adherence. Thus in the beginning of treatment, assessment on how patient would be ready to take medication, existing any limitations such as mental illness or active drug use, understanding of disease and regimen, social support and patient schedule, should be asses. Clinicians have to educate patient starting on HIV treatment for having very low missed doses, and this was based on evidence we have from a decades ago. By that time, treatment regimens were more complex. Lowering the threshold of adherence would not be possible because allowing for missed dose will only favor to poor compliance within time. Then, continuous support and intervention during treatment are needed to maintain high level of adherence to HAART intake

Performance of Cpred/Cobs concentration ratios as a metric reflecting adherence to antidepressant drug therapy

Background: Nonadherence is very common among subjects undergoing pharmacotherapy for schizophrenia and depression. This study aimed to evaluate the performance of the ratio of the nonlinear mixed effects pharmacokinetic model predicted concentration to observed drug concentration (ratio of population predicted to observed concentration (Cpred/Cobs) and ratio of individual predicted to observed concentration (Cipred/Cobs) as a measure of erratic drug exposure, driven primarily by variable execution of the dosage regimen and unknown true dosage history. Methods: Modeling and simulation approaches in conjunction with dosage history information from the Medication Event Monitoring System (MEMS, provided by the "Depression: The search for treatment relevant phenotypes" study), was applied to evaluate the consistency of exposure via simulation studies with scenarios representing a long half-life drug (escitalopram). Adherence rates were calculated based on the percentage of the prescribed doses actually taken correctly during the treatment window of interest. The association between Cpred/Cobs, Cipred/Cobs ratio, and adherence rate was evaluated under various assumptions of known dosing history. Results: Simulations for those scenarios representing a known dosing history were generated from historical MEMS data. Simulations of a long half-life drug exhibited a trend for overprediction of concentrations in patients with a low percentage of doses taken and underprediction of concentrations in patients taking more than their prescribed number of doses. Overall, the ratios did not predict adherence well, except when the true adherence rates were extremely high (greater than 100% of prescribed doses) or extremely low (complete nonadherence). In general, the Cipred/Cobs ratio was a better predictor of adherence rate than the Cpred/Cobs ratio. Correct predictions of extreme (high, low) 7-day adherence rates using Cipred/Cobs were 73.8% and 64.0%. Conclusion: This simulation study demonstrated the limitations of the Cpred/obs and Cipred/obs ratios as metrics for actual dosage intake history, and identified that use of MEMS dosing history monitoring combined with sparse pharmacokinetic sampling is a more reliable approach. © 2011 Feng et al

Effects of Diet Composition and Insulin Resistance Status on Plasma Lipid Levels in a Weight Loss Intervention in Women.

BackgroundOptimal macronutrient distribution of weight loss diets has not been established. The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies, and insulin resistance status may interact with diet composition and affect weight loss and lipid responses.Methods and resultsOverweight and obese women (n=245) were enrolled in a 1-year behavioral weight loss intervention and randomly assigned to 1 of 3 study groups: a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich, higher fat (35% energy), lower carbohydrate (45% energy) diet. Blood samples and data available from 213 women at baseline and at 6 months were the focus of this analysis. Triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterol were quantified and compared between and within groups. Triglycerides decreased in all study arms at 6 months (P&lt;0.05). The walnut-rich diet increased high-density lipoprotein cholesterol more than either the lower fat or lower carbohydrate diet (P&lt;0.05). The walnut-rich diet also reduced low-density lipoprotein cholesterol in insulin-sensitive women, whereas the lower fat diet reduced both total cholesterol and high-density lipoprotein cholesterol in insulin-sensitive women (P&lt;0.05). Insulin sensitivity and C-reactive protein levels also improved.ConclusionsWeight loss was similar across the diet groups, although insulin-sensitive women lost more weight with a lower fat, higher carbohydrate diet versus a higher fat, lower carbohydrate diet. The walnut-rich, higher fat diet resulted in the most favorable changes in lipid levels.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01424007

What We Mean When We Talk About Adherence In Respiratory Medicine

The Respiratory Effectiveness Group (REG; www.effectivenessevaluation.org) supported the Expert Adherence Panel Meeting at which many of the concepts presented in this paper were first discussed. REG also supported the manuscript submission costs. ALD, EvG, and MdB have received funding from the European Community's 7th Framework (FP7/2007-2013) under grant agreement no. 282593. Teva supported the meeting costs at which the concepts in this paper were discussed by the co-authors and the open access publication fee for this article. The authors had full editorial control over the ideas presented.Peer reviewedPublisher PD

Adherence to secondary stroke prevention strategies - Results from the German stroke data bank

Only very limited data are available concerning patient adherence to antithrombotic medication intended to prevent a recurrent stroke. Reduced adherence and compliance could significantly influence the effects of any stroke prevention strategies. This study from a large stroke data bank provides representative data concerning the rate of stroke victims adhering to their recommended preventive medication. During a 2-year period beginning January 1, 1998, all patients with acute stroke or TIA in 23 neurological departments with an acute stroke unit were included in the German Stroke Data Bank. Data were collected prospectively, reviewed, validated and processed in a central data management unit. Only 12 centers with a follow-up rate of 80% or higher were included in this evaluation. 3,420 patients were followed up after 3 months, and 2,640 patients were followed up one year after their stroke. After one year, 96% of all patients reported still adhere to at least one medical stroke prevention strategy. Of the patients receiving aspirin at discharge, 92.6% reported to use that medication after 3 months and 84% after one year, while 81.6 and 61.6% were the respective figures for clopidogrel, and 85.2 and 77.4% for oral anticoagulation. Most patients who changed medication switched from aspirin to clopidogrel. Under the conditions of this observational study, adherence to stroke prevention strategies is excellent. The highest adherence rate is noticed for aspirin and oral anticoagulation. After one year, very few patients stopped taking stroke preventive medication. Copyright (C) 2003 S. Karger AG, Basel