Electronic Medication Event Monitoring System Research Articles

Medication intake reminders via a smartphone app improve real-world adherence to oral anticoagulation in atrial fibrillation patients

Abstract Introduction Treatment with oral anticoagulation (OAC) is one of the main pillars in managing atrial fibrillation (AF). Education and intake monitoring are recommended to improve therapy adherence to OAC. Over the past few years, the importance of smart devices has increased, opening up new potential for patient education and better patient follow-up. Purpose We wanted to evaluate the usage of a medication module of an in-house developed application, AF-EduApp, and its effect on patients’ therapy adherence to OAC. Methods The AF-EduApp multicenter study included 152 AF patients. The educational AF-EduApp contains, besides other modules, a medication module with the possibility to add a medication list. Patients also had the possibility to configure pill intake reminders which they could easily tick off. Adherence was calculated as the proportion of days that the medication was correctly taken, as indicated by the patient. This was compared with adherence measured by the Electronic Medication Event Monitoring System (MEMS, Aardex Group, Liège), which formed the primary outcome of this study. The MEMS cap registered the date and time of bottle opening and was used at baseline and after 12 months, each time for a monitoring period of 3 months (M1 respectively M2). Regimen adherence was defined as the proportion of days with the correct number of openings as recorded by MEMS. Results The 152 patients (Age: 68.8 ±6.7 years; Time since AF diagnosis: 5.1 ±6.6 years) used the application on 130.1 ±144.7 days during a mean follow-up of 386.8 ±108.1 days. A total of 137 patients were on OAC, of whom 87 patients set a reminder for the OAC in their medication list. If based on checking off the reminder, patients had a median therapy adherence of only 5.6% (IQR: 0.2-64.3%). This contrasts with a high regimen adherence based on MEMS: in 84 patients who completed both monitoring periods, adherence was 94.5 ±7.0% at M1 and 94.1 ±6.6% at M2 (p=0.266 between M1 and M2). At M1, there was already a trend towards a significant difference in MEMS regimen adherence between patients who did or did not set a reminder (96.3 ±4.8% vs 93.1 ±8.0%, n=84; p=0.067). At M2, patients who set a reminder took their medication significantly better than those who did not (96.2 ±5.3% vs 92.6 ±7.1%; p=0.048) (Fig 1). Conclusion The medication module was used by most of the patients, and 63.5% installed an intake reminder for at least their OAC therapy. However, checking off reminders is rarely done and cannot be used to judge adherence. On the other hand, patients who installed a reminder had a significantly higher real-world regimen adherence for OAC compared to patients who did not set a reminder. Medication intake reminders can contribute to improving adherence to OAC therapy.MEMS based real-world regimen adherence

Adherence to oral anticoagulation measured by electronic monitoring in a Belgian atrial fibrillation population

IntroductionStroke prevention using oral anticoagulation (OAC) is the first management priority in atrial fibrillation (AF). Despite the importance of good therapy adherence, real-world adherence is still suboptimal. Patient education and adherence monitoring with new technologies are recommended. The main purpose of this sub-analysis of the AF-EduCare trial was to evaluate the effect of personalized follow-up strategies on adherence to OAC.MethodsRegimen adherence was monitored by the electronic Medication Event Monitoring System cap at the start of the trial (M1) and after 12 months (M2), each for three months. Patients were part of one of three education groups (In-person, Online or App-based) or the standard care (SC) group. All are qualified for OAC therapy.ResultsA total of 768 patients were evaluated (11.8% SC vs. 86.8% any education group, mean age: 70.1 ± 7.9 years). Patients were taking non-vitamin K OAC (once daily 53.8%; twice daily 35.9%) or vitamin K antagonists (9.4%), equally distributed over the different study arms (p = 0.457). Mean therapy adherence was high (M1:93.8 ± 10.8%; M2:94.1 ± 10.1%). During both monitoring periods, the education group scored significantly higher than SC (M1:94.2 ± 10.0% vs. 91.3 ± 15.0%; p = 0.027; M2:94.4 ± 9.3% vs. 91.6 ± 14.0%; p = 0.006). More patients in the In-person and Online groups were able to keep or improve their adherence to > 90% compared to the SC.ConclusionOverall adherence to OAC in all study groups, even in SC, was very high, without attrition over time. Nevertheless, targeted education led to a small but significantly improved adherence compared to SC.Graphical

Adherence to oral anticoagulation in a Belgium atrial fibrillation population measured by a medical event monitoring system

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): The AF-EduCare study is a project supported by the Fund for Scientific Research, Flanders (T002917N). The AF-EduApp study is supported by an BMS/Pfizer European Thrombosis Investigator Initiated Research Program (ERISTA) grant. Background Treatment with oral anticoagulation (OAC) is one of the main pillars in the management of atrial fibrillation (AF). Therapy adherence to both VKA and NOAC is important. Education and intake monitoring are recommended to improve therapy adherence. Purpose The main purpose of this project was to evaluate the effect of personalized follow-up strategies on therapy adherence to OAC in AF patients. Methods In a multicentre, Belgian randomized controlled trial, the AF-EduCare/AF-EduApp study, the effect of different personalized education strategies (i.e. in-person, online or app-based education) is evaluated on clinical outcome parameters of AF patients compared to standard care (SC). One of the outcome parameters is therapy adherence to OAC. During the first 3 months of the trial, patients’ adherence to NOAC or VKA was measured with the Electronic Medication Event Monitoring System (MEMS). The MEMS cap fits on a medication bottle and registers the date and time of every bottle opening. Regimen adherence was defined as the the number of days with the correct number of openings according to the specific OAC regimen divided by the total number of monitored days. As dabigatran has to be stored in the original package to protect it from moisture and VKAs have a variable scheme between patients, a proxy-medication (i.e. another oral drug that needed to be taken once or twice daily and on the same moment of the day as dabigatran or VKA) was chosen to measure medication adherence. Patients in the education groups received a MEMS cap with LCD screen providing direct feedback by showing the number of openings within 24h. A small sample of the SC group also received a MEMS cap as controls, but without LCD screen to minimally trigger these patients. Results A total of 593 AF patients underwent adherence monitoring, of which 514 (86.7%) in the intervention group and 79 (13.3%) in the SC group. The mean age was 70.1±7.7 years, mean time since AF diagnosis was 5.8±6.9 years, and mean CHA2DS2-VASc score was 3.2±1.5. Overall adherence was high: 94.8% of the patients had an adherence >80% and 80.9% had an adherence >90%. A small but significant difference in adherence was observed between the intervention groups and the standard care group (intervention group 97% (5-100); SC 96%(24-100); p=0.024; Figure1). Also between the four study groups a significant difference was seen (in-person 97% (93.5-99); online 98% (94-100); app-based 98% (92-99); p=0.049) driven by a significant difference between the online and SC group (p=0.009). Conclusion Overall adherence to OAC in all study groups and even in SC was high. The high adherence percentage in the SC group could be related to the Hawthorne effect of using the MEMS. Nevertheless, electronic monitoring and targeted education slightly improved therapy adherence further in the intervention groups.

Real-world adherence to non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation measured by an electronic medication event monitoring system

Abstract Background Non-vitamin K antagonist oral anticoagulants (NOACs) are recommended as first choice therapy for thrombo-embolic prevention in patients with non-valvular atrial fibrillation (AF) and an elevated CHA2DS2-VASc score. A critical determinant for both safety and effectiveness of NOAC treatment is adherence to the prescribed medication regimen. Real-life adherence is suboptimal for many cardiovascular drugs. Measuring and improving NOAC adherence is primordial for optimising AF care. Purpose We measured adherence to any of the four NOACs in a population of AF patients who participate to a clinical trial during which they received targeted education on AF and its treatment. Methods This analysis is part of a prospective, multicenter, randomized controlled trial which is currently ongoing at three Belgian hospitals (AF-EduCare study). Ambulatory or hospitalised AF patients of that trial, treated with a NOAC, and who received a short targeted education session about AF and NOAC therapy at initiation, form the study group of this analysis. Monitoring of NOAC intake was performed by an electronic Medication Event Monitoring System (MEMS), starting immediately after initiation of the study and the education session (for 3 months). A special cap fits on a medication bottle and records the exact date and time of bottle openings. An LCD screen on the cap displays the number of openings of the medication bottle over a period of 24 hours, providing feedback about the correct intake. Dabigatran was replaced by a proxy medication as Dabigatran should be stored in the original package in order to protect it from moisture. Regimen adherence was calculated as the number of days on which one bottle opening in case of Rivaroxaban or Edoxaban and two bottle openings in case of Apixaban or Dabigatran is/are registered, divided by the total number of monitored days and multiplied by 100. Results A total of 233 patients (mean age 71.0±7.7 years; 71.2% males; CHA2DS2-VASc score 3.4±1.5; mean duration of AF history 5.8±7.5 years) were given a MEMS. Of these patients 32.2%, 31.3%, 26.2% and 10.3% were respectively on Edoxaban, Apixaban, Rivaroxaban and Dabigatran. Regimen adherence for these NOACs was 95.9±9.3%, 91.6±13.7%, 95.6±5.6% and 94.0±7.1% respectively. Overall, 94.4% of the patients had an adherence >80% and 81.1% had an adherence >90%. Adherence for the once and twice daily regimens was 95.8±0.7% and 92.2±1.3%, respectively (p=0.0003; Mann-Whitney U test). Conclusions This is a first prospective study investigating adherence for all NOACs using electronic monitoring. In this sample of AF patients who underwent a targeted education session before the 3 month monitoring period, mean adherence to NOAC intake was >90% for all NOACS. This high adherence may be related to both the education and the use of MEMS, which provided direct feedback to the patient. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The AF-EduCare study is a project supported by the Fund for Scientific Research, Flanders (T002917N).

Using an Electronic Medication Event-Monitoring System for Antiretroviral Therapy Self-Management Among African American Women Living With HIV in Rural Florida: Cohort Study.

BackgroundHIV remains a significant health issue in the United States and disproportionately affects African Americans. African American women living with HIV (AAWH) experience a particularly high number of barriers when attempting to manage their HIV care, including antiretroviral therapy (ART) adherence. To enable the development and assessment of effective interventions that address these barriers to support ART adherence, there is a critical need to understand more fully the use of objective measures of ART adherence among AAWH, including electronic medication dispensers for real-time surveillance.ObjectiveThis study aimed to evaluate the use of the Wisepill medication event–monitoring system (MEMS) and compare the objective and subjective measures of ART adherence.MethodsWe conducted a 30-day exploratory pilot study of the MEMS among a convenience sample of community-dwelling AAWH (N=14) in rural Florida. AAWH were trained on the use of the MEMS to determine the feasibility of collecting, capturing, and manipulating the MEMS data for an objective measure of ART adherence. Self-reported sociodemographic information, including a self-reported measure of ART adherence, was also collected from AAWH.ResultsWe found that the majority of participants were successful at using the electronic MEMS. Daily use of the MEMS tended to be outside of the usual time participants took their medication. Three 30-day medication event patterns were found that characterized ART adherence, specifically uniform and nonuniform medication adherence and nonuniform medication nonadherence. There were relatively few MEMS disruptions among study participants. Overall, adjusted daily ART adherence was 81.08% and subjective ART adherence was 77.78%.ConclusionsThis pilot study on the use and evaluation of the Wisepill MEMS among AAWH in rural Florida is the first such study in the United States. The findings of this study are encouraging because 10 out of 12 participants consistently used the MEMS, there were relatively few failures, and objective adjusted daily and overall subjective ART adherence were very similar. On the basis of these findings, we think researchers should consider using the Wisepill MEMS in future studies of AAWH and people living with HIV in the United States after taking into account our practical suggestions. The following practical considerations are suggested when measuring objective medication adherence: (1) before using an MEMS, be familiar with the targeted populations’ characteristics; (2) choose an MEMS that aligns with the participants’ day-to-day activities; (3) ensure the MEMS’ features and resulting data support the research goals; (4) assess the match among the user’s ability, wireless features of the MEMS, and the geographic location of the participants; and (5) consider the cost of MEMS and the research budget.

Mobile medication manager application to improve adherence with immunosuppressive therapy in renal transplant recipients: A randomized controlled trial.

BackgroundNonadherence to immunosuppressive therapy after renal transplantation is associated with poor graft outcomes. We aimed to evaluate whether the use of the Adhere4U mobile medication manager application could improve adherence among renal transplant recipients ≥1 year posttransplantation. Adhere4U can provide medication reminders, monitor medication use, and provide information on immunosuppressants.MethodsWe conducted a prospective randomized controlled study to compare the rate of nonadherence to index immunosuppressant (tacrolimus or cyclosporine) in a group using the Adhere4U app (mobile group) and in another group receiving conventional care (control group). The primary outcome was the nonadherence rate, which was evaluated using an electronic medication event monitoring system during the 6-month intervention period. Our secondary outcome included self-reported adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) and the visual analog scale (VAS) based on a 4-week recall on days 28, 90, and 180. Longitudinal data of repeated measures of self-rated adherence were analyzed using generalized estimating equations (GEE) to compare the between-group difference in adherence change over time.ResultsBetween November 2013 and May 2015, 138 renal transplant recipients were randomly allocated to the control (n = 67) or the mobile group (n = 71). The overall nonadherence rate over the 6-month study period by electronic monitoring was 63.6%, with no between-group difference [mobile group, 65.0% (n = 39/60); control group, 62.1% (n = 36/58); odds ratio 1.14; 95% confidence interval 0.53–2.40; p = 0.89]. Self-rated nonadherence assessed using the BAASIS and VAS at baseline was 53.7% and 51.5%, respectively. Although the self-rated nonadherence by BAASIS of the mobile group was lower than the control group throughout the study period, there was no between-group difference in the change of nonadherence over time (χ2 = 2.82, df = 3, p = 0.42 by logistic GEE). There also was no significant between-group difference in the nonadherence by VAS (χ2 = 1.71, df = 3, p = 0.63 by logistic GEE) over time. The main limitation of this study was the low rate of patient engagement with the app among the mobile group. The rate of app use was 47.6% (31/65) at 28 days, 33.9% (19/56) at 90 days, and 11.5% (6/52) at 180 days.ConclusionsThe Adhere4U application did not improve adherence to immunosuppressive therapy. Our evidence is limited by the high rate of attrition. Further studies on strategies to facilitate patient engagement with mobile interventions are warranted.

Effect of Depression on Adherence to Oral PrEP Among Men and Women in East Africa.

Background:Low adherence can undermine the efficacy of daily oral pre-exposure prophylaxis (PrEP). Mental health conditions, particularly depression, could be associated with low PrEP adherence, especially for women.Setting:We analyzed data from 1013 Kenyan and Ugandan HIV-uninfected participants in the Partners Demonstration Project, an open-label study of PrEP delivered to HIV-uninfected members of serodiscordant couples.Methods:Participants completed quarterly visits over 2 years and were encouraged to use PrEP until their partners living with HIV had ≥6 months of antiretroviral therapy use (when viral suppression was expected). PrEP adherence was measured daily with electronic medication event monitoring system caps and dichotomized into low (<80% of expected bottle openings) and high adherence. Depression was assessed annually using the 16-item Hopkins Symptom Checklist screening tool; scores >1.75 indicate “probable depression.” The association between probable depression and PrEP adherence was assessed separately for men and women using generalized estimating equations and marginal structural models.Results:At enrollment, 39 (11.7% of 334) women and 64 (9.4% of 679) men reported symptoms indicating probable depression, and these proportions decreased during follow-up (P < 0.001 for women and men). Probable depression was significantly associated with low PrEP adherence among women (adjusted risk ratio = 1.77; 95% confidence interval: 1.14 to 2.77; P = 0.01); there was no association between depression and adherence among men (P = 0.50). Marginal structural models and sensitivity analyses confirmed these findings.Conclusions:Depression was relatively uncommon in this population and was an independent risk factor for low PrEP adherence among women. For PrEP programs targeting African women, integration of depression screening may improve PrEP effectiveness.

Over-adherence to capecitabine: a potential safety issue in breast and colorectal cancer patients.

The aim of the OCTO clinical study was to measure patients' adherence to capecitabine-based treatment. A cohort of ambulatory patients treated with capecitabine monotherapy for either locally advanced or metastatic, breast or colorectal cancer was monitored for 6 cycles. Adherence was assessed in all patients by self-completed questionnaires on disease, pill-count and pharmacological dosage of FBAL (metabolite of capecitabine); and in half of the cohort by electronic medication event monitoring systems (MEMS™) recording the opening times of the device. Forty patients were enrolled between November 2008 and September 2011 and treated by capecitabine for an average of 4.75 cycles (range 1-6). Hand-foot syndrome (HFS) was the most frequently reported toxicity (35% patients), and to a lesser extent fatigue and/or asthenia (21%), nausea and/or vomiting (13%) and diarrhea (11%). In the MEMS™ cohort, 20 patients were included. Patients' adherence was excellent with very few missing occasions (23/2272 records). Close analysis of MEMS™ data revealed unexpected medication patterns, such as patients taking extra days of medication beyond planned cycle, patients taking extra doses per day and patients missing a day of dosing and "compensating" by taking extra the following day (N = 7, 18%). A trend was found between over-adherence and high-grade toxicity (grades 3 and/or 4): OR 4.74 [0.65-45.2], p = 0.13 and higher AUC (p = 0.16). There was a trend towards increased AUC of FBAL in over-adherent patients (p = 0.16). Adherence to oral anticancer chemotherapy was found excellent in this population suggesting over-adherence to capecitabine and potential safety implications for outpatients' drugs.

Impact of combination antiretroviral therapy initiation on adherence to antituberculosis treatment.

BackgroundHealthcare workers are often reluctant to start combination antiretroviral therapy (ART) in patients receiving tuberculosis (TB) treatment because of the fear of high pill burden, immune reconstitution inflammatory syndrome, and side-effects.ObjectTo quantify changes in adherence to tuberculosis treatment following ART initiation.DesignA prospective observational cohort study of ART-naïve individuals with baseline CD4 count between 50 cells/mm3 and 350 cells/mm3 at start of TB treatment at a primary care clinic in Johannesburg, South Africa. Adherence to TB treatment was measured by pill count, self-report, and electronic Medication Event Monitoring System (eMEMS) before and after initiation of ART.ResultsART tended to negatively affect adherence to TB treatment, with an 8% – 10% decrease in the proportion of patients adherent according to pill count and an 18% – 22% decrease in the proportion of patients adherent according to eMEMS in the first month following ART initiation, independent of the cut-off used to define adherence (90%, 95% or 100%). Reasons for non-adherence were multifactorial, and employment was the only predictor for optimal adherence (adjusted odds ratio 4.11, 95% confidence interval 1.06–16.0).ConclusionAdherence support in the period immediately following ART initiation could optimise treatment outcomes for people living with TB and HIV.

Adherence to oral anticancer chemotherapy: What influences patients' over or non-adherence? Analysis of the OCTO study through quantitative-qualitative methods.

BackgroundNumerous oral anticancer chemotherapies are available. Non-adherence or over-adherence to these chemotherapies can lead to lowered efficacy and increased risk of adverse events. The objective of this study was to identify patients’ adherence profiles using a qualitative–quantitative method.MethodsA capecitabine treatment was initiated for 38 patients with advanced breast or colorectal cancer. At inclusion, information on patients’ beliefs was reported using a questionnaire. Later, Information on patients’ relation to treatment was obtained from a sub-group during an interview with a sociologist. Questionnaires were analyzed using Multiple Classification Analysis to cluster patients. Treatment adherence was evaluated by an electronic medication event monitoring systems (MEMS caps) and then correlated with patient clusters. Interviews were analyzed to complete and explain results.Results38 patients were enrolled between 2008 and 2011 and completed the questionnaire. Twenty had adherence measured with MEMS caps all along treatment. Between 4 and 6 months after inclusion, 16 patients were interviewed. Patient profile B (retired, with a regular life, surrounded by a relative’s attention to drug adherence, with a low educational level) was statistically associated with adequate adherence (p = 0.049). A tendency for lower adherence was observed among more highly educated patients with an irregular, active life (NS). All patients taking capecitabine demonstrated a risk of over-adherence, potentiating side effects.ConclusionsThese encouraging primary results suggest that further studies should be undertaken and that educational programs tailored to patient profiles should be evaluated to enhance adherence for those who need it and to empower all patients to manage treatment side effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-015-1231-8) contains supplementary material, which is available to authorized users.

Studying the Impact of Imatinib Mesylate (IM) Adherence in Chronic Myeloid Leukemia (CML) patients’ Responses in the State of Qatar

Background:The introduction of Imatinib Mesylate (IM) has revolutionized the outcome of Chronic Myeloid Leukemia (CML) patients. However, the success of the rationally designed therapy is tempered by the understanding that a substantial proportion of CML patients fail treatment.In Qatar, 54% of CML patients do fail IM according to European leukemia net (ELN) recommendations 2013. Point mutation & unique tri-nucleotide insertions explained only 14% of treatment failure. Additional chromosomal abnormalities were the most common cause of IM failure in our patients’ cohort & were documented in 50% of cases. 14% of patients stopped IM due to intolerance & the mechanisms of resistance remained unknown in 28% of patients. Other cause such as patients’ adherence to IM is being prospectively investigated. Therefore, Non adherence to IM must be ruled out as a possible cause of lack of optimal response before considering such patients to be IM-resistant & switching them to next-line treatment.Aim:To correlate between CML patients’ adherence to IM treatment & their responses and identify the factors affecting non-adherence.Methods:36 CML patients (5 citizens & 31 residents) are consented into the study. adherence to Imatinib was assessed using four different techniques: calculation of the Medication Possession Ratio (MPR), electronic Medical Records (eMR), survey questionnaire & Medication Event Monitoring System (MEMS).MPR is defined as the sum of the days’ supply of medication divided by the number of days between the first fill & the last refill. Patients medications history was obtained from questionnaire, pharmacy electronic Medical record (eMR) & studying drug – drug interactions was done using MICROMEDEX® 1.0 (Healthcare Series).The Questionnaire used to identify potential factors revolving around the patient’s lifestyle, affordability & knowledge related to IM, in addition to standardized evaluation based on the 9-item Morisky Medication Adherence Scale (MMAS) ranging from 1 to 13. Scores ≤10 indicates non adherence whereas ≥ 11 indicates adherence.Patient adherence was tracked electronically using the Medication Electronic Monitoring System (MEMS) that provided real time measures of adherence for a period up to 4 months.95 Peripheral blood (PB) samples were collected & the level of BCR-ABL1 transcripts was measured via RT-QPCR.The ELN 2013 recommendations for the management of CML was adopted & employed in this study to assess the response/resistance of patients to treatment. Responses were defined at the haematological, cytogenetic & molecular levels. Patients responses were classified into optimal, suboptimal or failure.Results:Out of 36 patients, 23 patients were adherent (MMAS, MPR &MEMS were ≥ 80%) & 13 patients were classified as non-adherent (MMAS, MPR &MEMS were <80 % )All adherent patients were optimally responded to the treatment (achieved CCyR & MMR) while the 13 non-adherent patients failed the treatment (2 patients were intolerant, 9 patients did not achieved CCyR & molecular response & 2 patients developed additional chromosomal abnormalities.Questionnaire feedback results showed that 69% patients could not afford to pay the remaining 10% of its cost, the other factors such as lack of knowledge (comprehensive & insight of illness) & illiteracy were observed in 35% & 30% of patients respectively.Discussion & conclusion:Due to high rate of Imatinib failure in Qatar, patient’s adherence to treatment was studied. Non adherence to the treatment was one of the most common causes of Imatinib failure in our patients’ cohort & was documented in 36% of cases.Economic factor (Unaffordable drug price) was one of the main causes of non-adherence & efforts should be made locally to improve access to medications for cancer diseases.Other risk factors associated with poor adherence can be improved by close monitoring & dose adjustment. Monitoring risk factors for poor adherence in combination with patient education that includes direct communication between the health care teams doctors, nurses pharmacists & patients are essential components for maximizing the benefits of TKI therapy & could rectify this problem.Our preliminary results showed that patients’ response to treatment may be directly linked to patient adherence to the treatment. However, further in-depth & specific analysis may be necessary in a larger cohort. DisclosuresAl-Dewik:Hamad Medical Corporation (HMC): Employment, HMC Medical Director’s Grant Competition (GC) 1013A Patents & Royalties, Research Funding. Morsi:HMC: Employment, Research Funding. Ghasoub:HMC: Employment, Research Funding.

Predictors of adherence to glaucoma treatment in a multisite study.

Poor adherence hinders glaucoma treatment. Studies have identified demographic and clinical predictors of adherence but fewer psychological variables. We examined predictors from four health behavior theories and past research. In the baseline phase of a three-site adherence study, before any intervention, 201 participants used electronic Medication Event Monitoring System (MEMS) bottles to monitor eyedrop use for 2 months, and completed questionnaires including self-reported adherence. MEMS showed 79% adherence and self-report 94% (0.5-1.5 missed weekly doses), but they correlated only r(s) = 0.31. Self-efficacy, motivation, dose frequency, and nonminority race/ethnicity predicted 35% of variance in MEMS. Cues to action, self-efficacy, and intention predicted 20% of variance in self-reported adherence. Self-efficacy, motivation, intention, cues to action, dose frequency, and race/ethnicity each independently predicted adherence. Predictors from all theories were supported in bivariate analyses, but additional study is needed. Researchers and clinicians should consider psychological predictors of adherence. (ClinicalTrials.gov ID# NCT01409421.).

Nonadherence with ambulatory saliva sampling is associated with biased salivary testosterone estimates.

Nonadherence with scheduled saliva sampling, as encountered in ambulatory settings, can bias the estimation of salivary cortisol concentrations. This study is the first to estimate if such nonadherence is also associated with biased salivary testosterone concentration estimates. Using a standard ambulatory saliva-sampling protocol, we instructed pregnant women to collect saliva samples on two consecutive days at awakening, 1100h, 1500h, 2000h, and 2200h. We estimated testosterone concentrations in the saliva samples and participants' actual sampling times with an electronic medication event-monitoring system. We classified a saliva sample as adherent if it was sampled within a specific time window relative to its scheduled sampling time. We used a mixed-model analysis to distinguish between trait (number of adherent saliva samples per participant) and state (adherence status of a specific sample) adherence. We included 60 pregnant women in this study. Seventy-five percent (448 of 600) of the scheduled samples indicated adherence with the sampling schedule. Participants' trait adherence was associated with their diurnal profiles of salivary testosterone estimates; that is, adherent participants had higher salivary testosterone estimates compared with nonadherent participants, F(1,58)=5.41, p=0.023, Cohen's d=0.67. The state adherence of a sample was associated with the salivary testosterone estimate of the related sample, F(1,469)=4.48, p=0.035, Cohen's d=0.20, with delayed sampling associated with lower salivary testosterone estimates. The results suggest that common ambulatory nonadherence with scheduled saliva sampling is associated with biased salivary testosterone estimates. They will inform further studies estimating salivary testosterone with ambulatory saliva-sampling designs and highlight the relevance of strategies to improve or confirm adherence, beyond routinely used instructions.

Increased Medication Compliance of Liver Transplant Patients Switched From a Twice-Daily to a Once-Daily Tacrolimus-Based Immunosuppressive Regimen

BackgroundCompliance with immunosuppressive therapy plays a major role in the long-term success of liver transplantation. Thus, the development of strategies to promote compliance of liver transplant patients and its evaluation over time are of particular interest. ObjectiveThe main objective of this study was to compare medication compliance rates among liver transplant patients over time after transplantation where switched from a twice- to once-daily tacrolimus-based regimen. MethodsSixty-five liver transplant patients being administered tacrolimus-based therapy were classified into three subgroups with regard to time posttransplantation. Medication compliance with tacrolimus-based therapy was measured using an electronic medication event monitoring system over a 12-month period: for 6 months tacrolimus was administered twice-daily and for 6 months, once-daily. Dosing, taking, and timing compliance as well as drug holidays were compared intra-individually between twice- and once-daily intake and among the three subgroups. In addition, patient compliance and quality of life were evaluated using questionnaires. ResultsA per protocol analysis of electronically obtained data showed 63 patients to be eligible. The resulting dosing, taking, and timing compliance rates of the patients were higher during the once-daily dosing period. No significant differences in compliance rates with tacrolimus therapy were observed among three subgroups independent of the dosing regimen. More patients failed the correct timing of the evening compared to the morning dose. Missing doses occurred particularly during weekends. Compliance variables measured by questionnaires (Morisky score, self-report, Medication Experience Scale for Immunosuppressants (MESI) score) and the Hospital Anxiety and Depression Scale score were similar in the two dosing periods. The short-form health survey (SF-36) score was higher with once-daily intake. ConclusionThe high measured compliance rates did not vary significantly dependent upon the time after transplantation. Nevertheless, compliance rates were greater using once-daily tacrolimus dosing.

Patient compliance to oral anticancer chemotherapy evaluated in breast and colorectal cancer patients receiving capecitabine: The OCTO study.

e13594 Background: Given the expanding use of oral chemotherapies, optimal compliance to treatment is critical to achieve the best clinical outcome in terms of efficacy and safety. The aim of the OCTO clinical study was to measure patient compliance, either electronically or by self-assessment, to capecitabine-based treatment. Methods: A cohort of patients with either locally advanced or metastatic, breast or colorectal, cancer were monitored for 6 cycles, and ambulatory treated with monotherapy of capecitabine (Xeloda). Treatment was prescribed at 1250 mg/m² as a combination of 500 and 150 mg pills, taken twice daily for 14 days every 3-week cycle. Tumor response was evaluated after 3 and 6 cycles using the RECIST criteria. Toxicity was evaluated using the NCI CTC scale. Compliance was assessed in all patients by self-completed questionnaires on disease, treatment and ambulatory management of side effects; and in half of the cohort by electronic medication event monitoring systems (MEMS) recording the opening times of the pill bottle. Results: Forty patients were enrolled between November 2008 and September 2011 and treated by capecitabine for an average of 4.75 cycles (range: 1-6). 63% patients completed 6 cycles, 22% and 15% patients discontinued due to respectively disease progression and adverse events. Best tumor response was evaluable in 35 patients: 23% had partial response, 54% stable disease and 23% progressed. Hand-foot syndrome was the most reported toxicity (77% patients), and to a lesser extent diarrhea (45%), nausea (30%) and vomiting (30%). In the MEMS cohort, 20 patients were included. Patient compliance was excellent with very few missing occasions (23/2272 records). Timing of morning doses was less variable (p=0.03) than timing of evening ones. Thirty-eight questionnaires were returned. Autonomy of ambulatory oral treatment was appreciated by 54% patients, while resulting in anxiety in 6%. Only 39% patients were concerned by the potential impact of non-compliance while 45% declined answering the question. Conclusions: Compliance to oral anticancer chemotherapy was found excellent in this population, with few deviations from prescription.

The Role of Depression in Medication Adherence Among Heart Failure Patients

The purpose of the study was to explore the association between depression and medication adherence in heart failure (HF) patients. Studies have shown that people with depression are likely to be nonadherent to their prescribed medication treatment. But other studies suggest that nonadherence may be overestimated by people with depression. A total of 244 adults with Stage C HF completed the study. Self-reported medication adherence was obtained using the Basel Assessment of Adherence Scale (BAAS); objective data on medication adherence were collected using the electronic Medication Event Monitoring System (MEMS). Depression was measured via self-report with the Patient Health Questionnaire (PHQ-9). There was a significant difference between depressed and nondepressed participants in self-reported medication nonadherence (p = .008), but not in objectively measured medication nonadherence (p = .72). The depressed sample was 2.3 times more likely to self-report poor medication adherence than those who were nondepressed (p = .006).

Adherence to oral anticancer drugs (OAD) in patients (pts) with metastatic renal cancer (mRCC): First results of the prospective observational multicenter IPSOC study (Investigating Patient Satisfaction with Oral Anti-cancer Treatment).

4622 Background: Patient adherence to oral therapy is a critical issue in cancer treatment. The aim of this study is to investigate the prevalence and severity of non-adherence to OAD in mRCC and to identify factors predictive of non-adherence. Methods: Prospective observational multicenter trial performed at 11 Belgian academic and non-academic centers. All pts with mRCC starting OADs (sunitinib, pazopanib, everolimus or sorafenib) are eligible for the study. Pts are contacted by phone at baseline and at 1, 3, 6 and 12 months. At each contact, pts are asked to complete questionnaires investigating 1) medication adherence (MMAS), 2) patient satisfaction with treatment (CTSQ) and with treatment education (PS-CaTE), 3) the extent of information desire (EID), 4) quality of life (FACT-G and FKSI) and 5) the role of the pharmacist (SWiP). Adherence is measured using an electronic medication event monitoring system (MEMS, Aardex). Results: Between 02/2011 and 11/2011, 49 pts (m: 33, f: 16) with a median age of 63 years (range 25 - 87) have participated in the IPSOC study. Twenty-nine pts (64%) were treated with an OAD in first-line, 15 pts (33%) in second-line. With a median follow-up of 131 days (range 2 - 313) 45 pts (92%) claimed to be fully adherent to their treatment (based on MMAS and CTSQ data). Four patients indicated to have missed at least one dose, of whom two indicated they occasionally forgot their medication and two others interrupted treatment because of side effects. Based on MEMS data, mean adherence, defined as the percentage of days with at least the prescribed number of dosage taken, was 98.91%. Conclusions: The IPSOC study, the first to examine adherence to OAD among mRCC pts, shows that mRCC pts are almost fully adherent to treatment recommendations. This seems to be in contrast to adherence data for other, long-lasting, anti-cancer treatments. Further investigations will focus on the question whether extensive counseling and participation in side-effect programs contribute to the high percentage of adherence in this study.

Do automated text messages increase adherence to acne therapy? Results of a randomized, controlled trial

Acne is a common skin condition often requiring complex therapeutic regimens. Patient nonadherence to prescribed medication regimens is a factor in treatment failure. The goal of this study was to determine if daily automated text messages would result in increased adherence to recommended use of topical acne medication and consequently greater improvement in acne. Forty patients with mild to moderate acne were prescribed clindamycin/benzoyl peroxide 1%/5% gel in the mornings and adapalene 0.3% gel in the evenings for 12 weeks. Each medication tube was fitted with an electronic Medication Event Monitoring System cap (MEMS, Aardex Group, Sion, Switzerland) (to record the date and time of every opening/closing of the tube). Twenty patients were randomly assigned to receive customized twice-daily text messages instructing them to apply their morning and evening medication. The remainder of patients (N = 20), who did not receive text messages, served as control subjects. Mean adherence rates for the correct application of both medications on a daily basis over 12 weeks was 33.9% for patients in the reminder group and 36.5% for patients in the control group (P = .75). Patients in both groups had similar clinical improvement of their acne. The small sample size may limit the ability to detect differences between the study groups. Electronic reminders in the form of daily, customized text messages were not associated with significant differences in adherence to topical medications in patients with mild to moderate acne and had no significant effect on therapeutic response.

Optimal recall period in assessing the adherence to antihypertensive therapy: a pilot study

To evaluate the validity of patient self-reported adherence, and to find the optimal length of recall period which best reflects the long-term adherence pattern of the patient. Patients were recruited from a general practitioner's practice in a Hungarian town. In this prospective study 30 patients, who had already been on antihypertensive treatment, were involved. The study was designed to monitor one antihypertensive medication per patient for 3 months. Patients received a 3-month supply of one antihypertensive medication in an electronic Medication Event Monitoring System (MEMS). At the end of the study period patients completed a structured questionnaire regarding their medication taking behavior during the last 7, 14 and 30 days. The results measured with MEMS were considered as the reference value, and other measures were compared using the Bland-Altman method. Self-reported adherence, length of recall period, taking adherence and timing adherence measured by MEMS. Of the 30 patients included, 29 patients (13 males and 16 females) completed the study. The mean age of the patients was 60.6 years, ranging between 36 and 86 years. Patients were monitored for an average of 89 days (ranging between 49 and 106 days). Fifteen patients were on once daily, 9 patients were on twice daily, and 5 patients were on 3 times daily dosing schedule. The total expected number of medication taking events was 4,281. The MEMS caps recorded a total of 4,071 openings, which showed only a 3.56% deviation from the pill counts of the remaining tablets. The overall taking adherence was 95.1%, timing adherence was 75.2%. Patients' adherence report using a visual analog scale and reporting the number of missed doses became more accurate as the length of the recall period increased. Increased number of chronically taken medications was associated with better adherence. Increased dosing frequency of the observed antihypertensive medication resulted in decreased adherence. The results showed that the length of the recall period influences the accuracy of self-reported adherence. Patients seem to be able to report more precisely their medication taking behavior regarding a 30 day period than a 7 day period.

Enhancing adherence to capecitabine chemotherapy by means of multidisciplinary pharmaceutical care

PurposeIn this prospective multi-centre observational cohort study, we investigated the effect of an intensified multidisciplinary pharmaceutical care programme on the adherence of cancer patients treated with capecitabine, a prodrug of fluorouracil.Patients and methodsTwenty-four colorectal and 24 breast cancer patients participated in this study. Patients of the control group (n = 24) received standard care, patients of the intervention group (n = 24) received intensified pharmaceutical care consisting of written and spoken information. Adherence to capecitabine chemotherapy was measured using an electronic medication event monitoring system (MEMS™).ResultsPatients in the intervention group exhibited an enhanced but not significantly different mean overall adherence compared to the control group (97.9% vs 90.5%, p = 0.069). Mean daily adherence was significantly higher in the intervention group (96.8% vs 87.2%, p = 0.029). Variability of both adherence parameters was considerably reduced when pharmaceutical care was provided. At the end of the observation period of 126 days, the probability of still being treated with capecitabine was found to be 48% in the control group and 83% in the intervention group (p = 0.019, log-rank test). The relative risk for a deviating drug intake interval, i.e. <10 or >14 instead of 12 h, in the intervention group was found to be 0.51 (95% CI, 0.46–0.56) compared with the control group (p < 0.05, Chi-square test).ConclusionsThe provision of intensified pharmaceutical care can enhance adherence to and prolong treatment with capecitabine. The results underline the importance of multidisciplinary care to assure the effectiveness of oral chemotherapy.