Medication adherence in patients with type 2 diabetes after disability onset: a difference-in-differences analysis using nationwide data.

BACKGROUND: Effectively managing the coexistence of both diabetes and disability necessitates substantial effort. Whether disability onset affects adherence to type 2 diabetes medication remains unclear. This study investigated whether disability onset reduces such adherence and whether any reduction varies by disability type. METHODS: This study used the National Disability Registry and National Health Insurance Research Database from Taiwan to identify patients with type 2 diabetes who subsequently developed a disability from 2013 to 2020; these patients were matched with patients with type 2 diabetes without disability onset during the study period. Type 2 diabetes medication adherence was measured using the medication possession ratio (MPR). A difference-in-differences analysis was performed to determine the effect of disability onset on the MPR. RESULTS: The difference-in-differences analysis revealed that disability onset caused a reduction of 5.76% in the 1-year MPR (P < 0.001) and 13.21% in the 2-year MPR (P < 0.001). Among all disability types, organ disabilities, multiple disabilities, rare diseases, and a persistent vegetative state exhibited the largest reductions in 2-year MPR. CONCLUSIONS: Policies aimed at improving medication adherence in individuals with disabilities should consider not only the specific disability type but also the distinct challenges and barriers these patients encounter in maintaining medication adherence.

Evaluation of HIV antiretroviral treatment adherence in 2019 using anonymized data from the French national health insurance claims data base: The COCOVIH study.

OBJECTIVE: Adherence to antiretroviral treatment (ART) plays a key role in achieving viral suppression in people living with HIV. We aimed to quantify ART adherence in the entire French HIV-infected population treated in 2019 and to determine factors of influence. METHODS: People living with HIV were identified using HIV diagnosis according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision criteria, HIV-specific laboratory tests, and prescription of antiretrovirals in 2019. Adherence was measured using the medication possession ratio (MPR; actual divided by theoretical number of tablets). Variables of interest included sex, age, type of ART, relevant comorbidities, and receiving supplementary universal health coverage for low-income citizens (CMUc). RESULTS: Of the n = 211 124 people living with HIV identified between 2006 and 2019, we included n = 140 607 on ART with two or more prescription fills in 2019 in this analysis. In total, 87.5% of people living with HIV were receiving ART in 2019. Mean ± standard deviation MPR was 82.5 ± 22.7%; 57% of people living with HIV had an MPR ≥90%, and 12.7% had an MPR <50%. Those with an MPR ≥90% significantly differed between males and females (59.1% and 52.8%, respectively; p < 0.001), and between CMUc recipients and non recipients (54.1% and 57.6%, respectively; p < 0.001). MPR ≥90% rate was lower for those with chronic nephropathy (50.2%), renal failure (46.6%), and tuberculosis (50.1%), and for those using psychoactive substances (52.3%). Factors associated with MPR ≥90% in multivariable analysis were older age, male sex, not receiving CMUc, more recent HIV diagnosis, and triple (vs. dual) ART. CONCLUSION: In 2019, the average MPR in people living with HIV was 82.5% according to the comprehensive French health care database. Besides sociodemographic variables such as older age, male sex, and not being a CMUc recipient (i.e. of low socioeconomic status), more recent HIV diagnosis and triple therapy were independently associated with better adherence, possibly reflecting advances in ART tolerability and dosing.

Quantification of Oversupply of Chronic Disease Medications among Patients Aged ≥55 Years in Japan.

Medication waste may be caused by medication oversupply; however, the degree of medication oversupply in Japan is unclear. This study aimed to quantify the degree of oversupply of chronic disease medications per patient, the proportion of oversupplied patients, and the excess days and costs of the oversupplied medications in Japan. This retrospective nationwide cohort study using a large insurance claims database from Japan was conducted in patients aged ≥55 years who received one or a combination of the following five classes of medications dispensed in FY 2019: third-generation calcium antagonists, angiotensin 2 receptor blockers, statins, dipeptidyl peptidase-4 inhibitors, and biguanides. Medications with the same ingredient having the same specification were treated as the same medication. Medication oversupply was defined as a medication possession ratio (MPR) during persistence >1.0. The proportions of oversupplied patients and excessively oversupplied patients with ≥30 excess days/year were approximately 16 and 1-2% for all drug classes, respectively. Three-quarters of the oversupplied patients had fewer excess day (≤14/year), and the median oversupplied medication cost was less than 1000 yen/year for all classes. However, there was a patient with oversupplied medication estimated as 983 excess days per year and a patient with oversupplied medication costs of nearly 90000 yen per year. Using the MPR and excess days as indicators, it is necessary to accelerate estimation of the oversupply per patient, as well as the development of patient intervention strategies and a national system to reduce medication oversupply.

Medication adherence and costs of medical care among patients with Parkinson's disease: an observational study using electronic medical records.

BACKGROUND: Adherence to antiparkinsonian drugs (APDs) is critical for patients with Parkinson's disease (PD), for which medication is the main therapeutic strategy. Previous studies have focused on specific disorders in a single system when assessing clinical factors affecting adherence to PD treatment, and no international comparative data are available on the medical costs for Chinese patients with PD. The present study aimed to evaluate medication adherence and its associated factors among Chinese patients with PD using a systematic approach and to explore the impact of adequate medication adherence on direct medical costs. METHODS: A retrospective analysis was conducted using the electronic medical records of patients with PD from a medical center in China. Patients with a minimum of two APD prescriptions from January 1, 2016 to August 15, 2018 were included. Medication possession ratio (MPR) and proportion of days covered were used to measure APD adherence. Multiple linear regression analysis was used to identify factors affecting APD adherence. Gamma regression analysis was used to explore the impact of APD adherence on direct medical costs. RESULTS: In total, 1,712 patients were included in the study, and the mean MPR was 0.68 (± 0.25). Increased number of APDs and all medications, and higher daily levodopa-equivalent doses resulted in higher MPR (mean difference [MD] = 0.04 [0.03-0.05]; MD = 0.02 [0.01-0.03]; MD = 0.03 [0.01-0.04], respectively); combined digestive system diseases, epilepsy, or older age resulted in lower MPR (MD = -0.06 [-0.09 to -0.03]; MD = -0.07 [-0.14 to -0.01]; MD = -0.02 [-0.03 to -0.01], respectively). Higher APD adherence resulted in higher direct medical costs, including APD and other outpatient costs. For a 0.3 increase in MPR, the two costs increased by $34.42 ($25.43-$43.41) and $14.63 ($4.86-$24.39) per year, respectively. CONCLUSIONS: APD adherence rate among Chinese patients with PD was moderate and related primarily to age, comorbidities, and healthcare costs. The factors should be considered when prescribing APDs.

Continuous aspirin treatment improves cardiovascular events and all-cause mortality in hemodialysis patients with peripheral artery disease.

BACKGROUND: Hemodialysis (HD) patients with peripheral arterial disease (PAD) are at heightened risk of adverse vascular events, and aspirin positively affects those outcomes. We aimed to investigate the association between different patterns of aspirin use and clinical vascular events in chronic HD patients with PAD. METHODS: This retrospective nationwide cohort study enrolled 758 chronic HD patients who had been diagnosed with PAD between January 1, 2008, and December 31, 2012, and followed up until the end of 2020. Patients were divided into three groups according to medication possession ratio (MPR) and continued use of aspirin (i.e., low MPR, high MPR but discontinuous prescription, and high MPR and continuous prescription). Percutaneous transluminal angioplasty (PTA), surgical bypass, lower leg amputation, cardiovascular events, cerebrovascular events, and all-cause mortality were evaluated. RESULTS: High MPR and continuous aspirin use had the lowest incidence of all-cause mortality and cardiovascular events compared with the two other groups, and it was significantly associated with low risk of PTA, surgical bypass, cardiovascular events, and all-cause mortality (aHR: 0.58 [0.41-0.83], 0.49 [0.25-0.95], 0.57 [0.40-0.81], and 0.70 [0.55-0.88], respectively). Kaplan-Meier analysis revealed that event-free rates of PTA, cardiovascular events, and all-cause mortality of patients with high MPR and continuous aspirin treatment were the highest among the three groups (p < 0.05). CONCLUSION: Among HD patients with PAD, high MPR and continuous aspirin use significantly reduced the risk of PTA, surgical bypass, cardiovascular events, and all-cause mortality and improved the event-free rates of PTA, cardiovascular events, and all-cause mortality during long-term follow-up.

A Retrospective Comparison of HIV Pre-exposure Prophylaxis (PrEP) Outcomes Between a Pharmacist-led Telehealth Clinic and In-person Clinic in a Veteran Population.

Pre-exposure prophylaxis (PrEP) reduces human immunodeficiency virus (HIV) transmission through sexual contact by at least 90% when taken as prescribed. This retrospective cohort study evaluated differences in adherence to PrEP medication and monitoring between the physician- and nurse practitioner (NP)-led in-person setting and the pharmacist-led telehealth setting among patients followed by the infectious diseases clinic at the VA Eastern Colorado Health Care System from July 2012 to February 2021. The primary outcomes were PrEP tablets filled per person-year, serum creatinine (SCr) tests per person-year, and HIV screens per person-year. Secondary outcomes included sexually transmitted infection (STI) screens per person-year and patients lost to follow-up.149 patients were included in the study, with 167 person-years in the in-person cohort and 153 person-years in the telehealth cohort. Adherence to PrEP medications and monitoring was similar between in-person and telehealth clinics. PrEP tablets filled per person-year was 324 in the in-person cohort and 321 in the telehealth cohort (RR = 0.99; 95% CI, 0.98-1.00). SCr screens per person-year was 3.51 in the in-person cohort and 3.37 in the telehealth cohort (RR = 0.96; 95% CI, 0.85-1.07). HIV screens per person-year was 3.55 in the in-person cohort and 3.38 in the telehealth cohort (RR = 0.95; 95% CI, 0.85-1.07). There were no new HIV infections. Additionally, patients were less likely to be lost to follow-up when followed via telehealth (11.9% vs. 30.0%), Χ2 (1, N = 149) = 6.85, p = 0.009. These findings indicate that pharmacist-driven delivery of PrEP via telehealth can be used to increase access to PrEP without sacrificing quality of care.

The real-world adherence of the first-line anti-osteoporosis medications in Taiwan: Visualize the gap between reality and expectations.

BACKGROUND: Adherence to anti-osteoporosis medications (AOMs) is crucial. National Health Insurance (NHI) in Taiwan has its own rules of reimbursement rule for AOMs. The midterm adherence remained inconclusive. Here we investigated the adherence according to the initially used AOMs, for three consecutive years. METHODS: The nationwide cohort study from 2008 to 2018, based on Taiwan's National Health Insurance Research Database, included 336,229 patients. Their adherence, indicated by medication possession ratio (MPR), to the initial AOMs was investigated yearly for three consecutive years. The overall MPRs (OMPR), including the switched AOMs, were also calculated in the first year. The Sankey diagram further visualized the patient flows toward different adherence according to the initial AOMs. RESULTS: The OMPR in the first year improved if the patients used AOMs with longer dosing intervals. 100%, 68.9%, 40.7%, and 34.0% of the patients started the treatment with zoledronate, denosumab, alendronate, and raloxifene, respectively, had OMPR ≥75% in the first year. In the 3rd year, only 20.89%, 24.13%, and 12.83% of the patients continuously treated with zoledronate, denosumab, and alendronate, respectively, had MPR ≥75%. From the Sankey diagram, we also observed that patients who had poor adherence at one year were inclined to have poor adherence or discontinue antiosteoporosis treatment in the next year. CONCLUSION: The initial AOMs and the observed adherence may provide clues for optimizing patient treatment. The real-world adherence in Taiwan was far from satisfactory in our study.

Adjuvant tamoxifen adherence in men with early-stage breast cancer.

BACKGROUND: Most breast cancers (BCs) in men are hormone receptor-positive. Adjuvant tamoxifen is part of the standard treatment of these patients. Small, single-institution studies have suggested that men have high rates of discontinuing adjuvant endocrine treatment. The authors examined rates of tamoxifen discontinuation and medication adherence in a large population-based cohort of male patients with BC. METHODS: In the Surveillance, Epidemiology, and End Results-Medicare database, male patients with invasive nonmetastatic BC, diagnosed between 2007 and 2013, who were ≥65 years old, had Part D coverage, and had tamoxifen prescriptions within 1 year of diagnosis were identified. Adherence was defined as a medication possession ratio of ≥80% among those patients who were filling tamoxifen prescriptions. Logistic regression model was used to assess predictors of tamoxifen adherence. RESULTS: A total of 451 patients met eligibility criteria. The median age at diagnosis was 75 years. The median follow-up was 32.5 months. The rates of tamoxifen discontinuation were 15.8%, 24.3%, 31.3%, 36.9%, and 48.3% at 1, 2, 3, 4, and 5 years after diagnosis, respectively. Among the men who were still taking tamoxifen, the corresponding adherence rates were 76.9%, 73.6%, 68.7%, 64.8%, and 60.2%. In the adjusted model, significant predictors of lower adherence included residing in a high poverty area (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.28-2.12) and a Charlson comorbidity score of ≥2 (OR, 0.46; 95% CI, 0.22-0.97). CONCLUSION: Older men with breast cancer have high rates of tamoxifen discontinuation, with 48% of all patients discontinuing tamoxifen before the end of year 5. Additionally, even among those patients continuing tamoxifen, a substantial number of patients are nonadherent. Further research should evaluate potentially modifiable reasons for treatment discontinuation and lack of adherence to tamoxifen.

Lipid-lowering drug adherence and combination therapy effects on gastrointestinal cancer in patients with dyslipidemia without diabetes: a retrospective cohort study in South Korea.

BACKGROUND: In aging populations, the number of people with high cholesterol levels is increasing. Appropriate management of high cholesterol levels with drugs such as statins may prevent secondary diseases. Despite many studies on the effects of statins on various types of cancer, the effectiveness of lipid-lowering therapy in preventing cancer remains controversial. This study aimed to evaluate its long-term effect on developing gastrointestinal (GI) cancer in patients with dyslipidemia. METHODS: This study used the National Health Insurance Sampling (NHIS) cohort data (2002-2015), which included patients with dyslipidemia without diabetes, and measured patients' adherence to lipid-lowering therapy using the medication possession ratio. We used the Cox proportional hazard ratio (HR) to identify the association between the continuity of lipid-lowering therapy and the risk of GI cancer. We also evaluated the association between a combination of lipid-lowering drugs and a reduced risk of GI cancer. RESULTS: A total of 49,351 patients were diagnosed with dyslipidemia, of which 579 were diagnosed with GI cancer. Patients with higher adherence to lipid-lowering therapy had a significantly reduced risk of GI cancer compared to patients without drugs, and high adherence was associated with a reduced incidence of all types of GI cancer. Specifically, the combination of statins and ezetimibe or fibrates appears to reduce GI cancer risk effectively. Overall, the continuity of lipid-lowering therapy had a protective effect on GI cancer in middle-aged and elderly patients with dyslipidemia compared to non-users. CONCLUSIONS: Our findings suggest that the continuity of lipid-lowering therapy is vital in patients with dyslipidemia. In addition, for individuals vulnerable to GI cancer, combination therapy may be associated with more effective protection against GI cancer. Healthcare providers need patient education and monitoring to improve drug adherence in patients with dyslipidemia.

Adherence with controller medication in adults with asthma - impact of hospital admission for acute exacerbation.

OBJECTIVE: Uncontrolled asthma is associated with higher risk of hospital admissions and death. Low adherence to inhaled corticosteroid (ICS), the cornerstone of asthma therapy, is well-documented. Our aim was to investigate if hospital admission with an acute exacerbation of asthma changes ICS adherence. METHODS: This retrospective cohort study comprises 241 patients hospitalized with an asthma exacerbation over 12 months (May 2019-April 2020). The primary outcome was proportion of ICS adherent patients, defined as Medication Possession Ratio (MPR) ≥80%, in the six-month period before and after admission. RESULTS: The pre- to post-admission proportion of ICS adherent patients increased from 10% to 13% (p = 0.25) and the mean ICS MPR increased from 34% to 42% (p < 0.001). Different patterns of post-discharge adherence were observed, as adherent patients remained adherent, while patients with poor pre-admission adherence increased their adherence during two months after discharge followed by a decline in MPR. Co-variates such as sex, age, body mass index (BMI), GINA 2020-treatment step did not predict improvement in adherence after discharge. CONCLUSIONS: Admission with an asthma exacerbation did not increase the proportion of patients adherent with controller medication, primarily ICS. Although an improvement in adherence was initially seen primarily in previously poorly adherent patients, this increase was transient as it decreased over time post-discharge.

Extent of non-adherence and non-persistence in asthma patients: analysis of a large claims data set.

OBJECTIVE: The objective of this study was to assess non-adherence (NA) and non-persistence (NP) to long-acting asthma medications in Germany by differentiating between measurement of NA in periods of therapy continuation and measurement of NP in therapy-naïve patients. METHODS: We analyzed treatment adherence to long-acting asthma medication using German claims data for periods of treatment continuation based on the medication possession ratio (MPR) and the proportion of days covered. Persistence was assessed in treatment-naïve patients. Outcomes were observed from the date of the first to the last prescription within a 12-month period. Both NA and NP analyses considered prescription supply, using either defined daily dosages, or prescribed daily dosages derived from a medical chart review. RESULTS: We identified 52,508 asthma patients (mean age: 40.1, 58.4% female) who received at least two long-acting asthma prescriptions within 12 months; 50,660 treatment-naïve patients were included in the NP analysis (mean age: 39.7, 58.8% female). The mean 12-month MPR was 38.5% (89.4% NA according to MPR ≤ 80%) and the average proportion of days covered was 40.4% (85.9% NA). Agent-specific MPR and NA rates varied between 31.8% (91.8% NA) and 56.2% (71.6% NA). The average weighted-MPR increased to 53.1% when using the prescribed daily dosage. Based on a > 90-day gap definition, 86.7% of patients were considered non-persistent after 12 months (>180: 72.3%). When using prescribed daily dosages, NP rates ranged from 66.7 to 78.5%. CONCLUSION: High levels of treatment NA and NP indicate a substantial need to improve adherence and persistence to long-acting asthma medication in Germany.

Cost analysis of acute care resource utilization among individuals with sickle cell disease in a middle-income country.

BACKGROUND: The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC). We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea in a specialized hematology center in Brazil. METHODS: The costs (US dollars) of emergency department (ED) and hospitalizations from SCD-related complications between 01.01.2018 and 06.30.2018 were ascertained using absorption and micro-costing approaches. The reasons for acute hospital visits were grouped as: 1) vaso-occlusive (VOC) pain, 2) infection, 3) anemia exacerbation, and 4) chronic organ damage complications. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period. RESULTS: In total, 1144 patients, median age 17 years (range 0-70), 903 (78.9%) with HbSS/HbSß0-thalassemia, 441 (38.5%) prescribed hydroxyurea, visited the ED, of whom 381 (33%) were admitted. VOC accounted for 64% of all ED visits and 60% of all admissions. Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2176.40/visit). Compared with other genotypes, individuals with HbSS/HbSß0-thalassemia were admitted more often (79% versus 21%, p < 0.0001), and their admission costs were higher ($1677.18 versus $1224.47/visit, p = 0.0001). Antibiotics and analgesics accounted for 43% and 42% of the total ED costs, respectively, while housing accounted for 46% of the total admission costs. Costs of ED visits not resulting in admissions were lower among HbSS/HbSß0-thalassemia individuals with hydroxyurea MPR ≥65% compared with visits by patients with MPR <65% ($98.16/visit versus $182.46/visit, p = 0.0007). No difference in admission costs were observed relative to hydroxyurea use. DISCUSSION: In a LMIC hematology-specialized center, VOCs accounted for most acute visits from patients with SCD, but costs were highest due to anemia exacerbation. Analgesics, antibiotics, and housing drove most expenses. Hydroxyurea may reduce ED costs among individuals with HbSS/HbSß0-thalassemia but is dependent on adherence level.

Medication adherence status among patients with neurological conditions and its association with quality of life.

BACKGROUND/AIM: Medication non-adherence may cause significant morbidity and mortality in patients with chronic diseases and may increase the economic burden on the healthcare system. The prevalence of neurological disorders is increasing in Malaysia; however, comprehensive data on medication adherence among Malaysian patients with these disorders is limited. This study was conducted to determine the association of medication non-adherence with quality of life in patients with neurological problems. METHODS: A cross-sectional survey was performed in 370 patients diagnosed with epilepsy, Parkinson's disease, stroke and Alzheimer's disease at Neurology clinic. Patients aged 18 years or older, without documented physical or psychiatric illness such as schizophrenia and major depression, were included. Patient-administered questionnaires, such as the Malaysian Medication Adherence Scale and Medication Possession Ratio were used to determine medication adherence. An established EQ-5D-3L questionnaire was used to determine quality of life. Data were analysed using descriptive and inferential analysis. RESULTS: The overall prevalence of medication non-adherence among patients with neurological disorders was 59.2%. Among these neuromedical diseases, 69.2% (n = 9/13) of Alzheimer's disease, 66.7% (n = 98/147) of epilepsy, 62.1% (n = 36/58) of Parkinson's disease and 48.7% (n = 74/152) of stroke patients were found non-adherent. There was a significant difference in EQ-5D index scores (p = 0.041) between adherent and non-adherent patients. CONCLUSION: A high prevalence of medication non-adherence was found among patients with neurological disorders. The rate of non-adherence varied among different neurological conditions. There was a significant difference in quality of life between adherent and non-adherent patients.

Alendronate medication possession ratio and the risk of second hip fracture: an 11-year population-based cohort study in Taiwan.

Alendronate is effective in preventing second hip fracture in osteoporotic patients. However, no consensus exists on the duration that is effective in preventing a second hip fracture. Our study demonstrated that risk can be reduced when the prescription is ≥ 6 months for the year following the index hip fracture. INTRODUCTION: Alendronate is effective in preventing second hip fracture in osteoporotic patients. However, no consensus exists on the accurate medication possession ratio (MPR) that is effective in preventing a second hip fracture. Our objective was to compare the risk of second hip fracture in patients treated with different MPR of alendronate. METHODS: In this population-based cohort study, data from National Health Insurance Research Database of Taiwan were analyzed. Patients 50 years and older who had an index hip fracture and were not receiving any osteoporotic medications before their fracture during 2000-2010 were included. The cohort consisted of 88,320 patients who were new alendronate users (n = 9278) and non-users (n = 79,042). Those without alendronate were matched 4:1 as the control group. Patients were subdivided into those with no medication, MPR < 25%, MPR 25-50%, MPR 50-75%, and MPR 75-100%. Cox proportional hazard models were used to calculate the adjusted hazard ratios for different MPRs of alendronate. RESULTS: After matching, 38,675 patients were included in this study; 20,363 (52.7%) were women, and 30,940 (80%) patients were without medication of alendronate. During follow-up on December 31, 2012, 2392 patients had a second hip fracture, for an incidence of 1449/100,000 person-years. Patients with alendronate MPR 50-75% had a lower risk of a second hip fracture compared to non-users (hazard ratio 0.66). When the MPR increased to 75-100%, the hazard ratio decreased to 0.61. CONCLUSIONS: In this population-based cohort study, risk of a second hip fracture can be reduced when the alendronate MPR is ≥ 50% for the year following the index hip fracture. As the MPR increases, the risk of a second hip fracture decreases.

Adherence in chronic hepatitis B: associations between medication possession ratio and adverse viral outcomes.

BACKGROUND: Antiviral therapy for chronic hepatitis B (CHB) is effective and can substantially reduce the risk of progressive liver disease and hepatocellular carcinoma but is often administered for an indefinite duration. Adherence has been shown in clinical trials to maximize the benefit of therapy and prevent the development of resistance, however the optimal threshold for predicting clinical outcomes has not been identified. The aim of this study was to analyse adherence using the medication possession ration (MPR) and its relation to virological outcomes in a large multi-centre hospital outpatient population, and guide development of an evidence-based threshold for optimal adherence. METHODS: Pharmacy and pathology records of patients dispensed CHB antiviral therapy from 4 major hospitals in Melbourne between 2010 and 2013 were extracted and analysed to determine their MPR and identify instances of unfavourable viral outcomes. Viral outcomes were classified categorically, with unfavourable outcomes including HBV DNA remaining detectable after 2 years treatment or experiencing viral breakthrough. The association between MPR and unfavourable outcomes was assessed according to various thresholds using ROC analysis and time-to-event regression. RESULTS: Six hundred forty-two individuals were included in the analysis. Median age was 46.6 years, 68% were male, 77% were born in Asia, and the median time on treatment was 27.5 months. The majority had favourable viral outcomes (91.06%), with most having undetectable HBV DNA at the end of the study period. The most common unfavourable outcome was a rise of < 1 log in HBV DNA (6.54% of the total), while 2.49% of participants experienced viral breakthrough. Adherence was linearly associated with favourable outcomes, with increasing risk of virological breakthrough as MPR fell. Decreasing the value of MPR, at which a cut-point was taken, was associated with a progressively larger reduction in the rate of unfavourable event; from a 60% reduction under a cut-point of 1.00 to a 79% reduction when the MPR cut-point was set at 0.8. CONCLUSION: Lower adherence as measured using the MPR was strongly associated with unfavourable therapeutic outcomes, including virological failure. Optimising adherence is therefore important for preventing viral rebound and potential complications such as antiviral resistance. The evidence of dose-response highlights the need for nuanced interventions.

Methods for Measuring Multiple Medication Adherence: A Systematic Review-Report of the ISPOR Medication Adherence and Persistence Special Interest Group.

BACKGROUND: A broad literature base exists for measuring medication adherence to monotherapeutic regimens, but publications are less extensive for measuring adherence to multiple medications. OBJECTIVES: To identify and characterize the multiple medication adherence (MMA) methods used in the literature. METHODS: A literature search was conducted using PubMed, PsycINFO, the International Pharmaceutical Abstracts, the Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library databases on methods used to measure MMA published between January 1973 and May 2015. A two-step screening process was used; all abstracts were screened by pairs of researchers independently, followed by a full-text review identifying the method for calculating MMA. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to conduct this systematic review. For studies that met the eligibility criteria, general study and adherence-specific characteristics and the number and type of MMA measurement methods were summarized. RESULTS: The 147 studies that were included originated from 32 countries, in 13 disease states. Of these studies, 26 used proportion of days covered, 23 used medication possession ratio, and 72 used self-reported questionnaires (e.g., the Morisky Scale) to assess MMA. About 50% of the studies included more than one method for measuring MMA, and different variations of medication possession ratio and proportion of days covered were used for measuring MMA. CONCLUSIONS: There appears to be no standardized method to measure MMA. With an increasing prevalence of polypharmacy, more efforts should be directed toward constructing robust measures suitable to evaluate adherence to complex regimens. Future research to understand the validity and reliability of MMA measures and their effects on objective clinical outcomes is also needed.

Pharmacy Refill Data are Poor Predictors of Virologic Treatment Outcomes in Adolescents with HIV in Botswana.

In adults living with HIV, pharmacy refill data are good predictors of virologic failure (VF). The utility of pharmacy refill data for predicting VF in adolescents has not been reported. We evaluated data from 291 adolescents on antiretroviral therapy. The main outcome measure was VF, defined as two consecutive HIV viral load measurements ≥ 400 copies/mL during 24-months of follow-up. Pharmacy refill non-adherence was defined as two consecutive refill adherence measurements < 95% during the same period. Fifty-three (18%) adolescents experienced VF. One hundred twenty-eight (44%) adolescents had refill non-adherence. Refill non-adherence had poor discriminative ability for indicating VF (receiver operating characteristic AUC = 0.60). Sensitivity and specificity for predicting VF was poor (60% (95% CI 46-74%) and 60% (95% CI 53-66%), respectively). The lack of a viable surrogate for VF in adolescents highlights the urgent need for more access to virologic testing and novel methods of monitoring adolescent treatment adherence.

Adherence and Concomitant Medication Use among Patients on Warfarin Therapy: Insight from a Large Pharmacy Dispensing Database in Japan.

Warfarin is a drug used for anticoagulation management, with a narrow therapeutic range and multiple drug-drug interactions. Adherence and proper use of concomitant medication are thus fundamental to the efficacy and safety of warfarin therapy. In 2012, we retrospectively analyzed data from three large-scale pharmacy chains in Japan. We included all adults (≥ 20 years old) with at least one record of warfarin dispensation. We examined patient demographic data, adherence as measured by medication possession ratio (MPR), and co-dispensation focusing on the number of concomitant dispensations and concurrent use of medications that increase bleeding risk. Thresholds of underadherence and overadherence were set at <0.9 and >1.1, considering the narrow therapeutic window. We reviewed 443007 warfarin dispensation records of 71340 individuals (median age, 73 years; 62% male). The MPR was 1.0 (interquartile range: 0.96-1.0), and underadherence and overadherence was found in 16.3 and 1.9% of individuals, respectively. The median number of co-dispensed drugs was eight at each pharmacy encounter, which did not differ by age group. Drugs associated with a high bleeding risk were dispensed in 40.0% of encounters and accounted for 16.4% of all co-dispensed drugs. In summary, we found optimal overall adherence, as assessed by MPR, among our Japanese study population, even when defining a strict cut-off value. However, polypharmacy was common in all age groups and medications with a high bleeding risk profile were often co-dispensed with warfarin. Future research addressing how these dispensation patterns affect patient outcome is warranted.

In search of a standard when analyzing medication adherence in patients with heart failure using claims data: a systematic review.

To determine and address medication non-adherence is important and may improve patient outcomes. Our aim was to perform a systematic review on the operationalization of adherence measures in patients with heart failure using claims data. We searched the MEDLINE, EMBASE, and Cochrane databases. A quality check of the full-text articles was performed using the Quality in Prognosis Studies tool. We included 28 studies. Eleven studies used the medication possession ratio, 15 the proportion of days covered, and six studies used own methods to calculate medication adherence. Almost all studies used an observation period of 1 year. Twenty-one studies considered angiotensin converting enzyme inhibitors or angiotensin receptor antagonists, 17 beta-blockers, 11 diuretics, eight mineralocorticoid receptor antagonists, six digitalis-glycosides, and six statins. Eight studies looked at single substance classes; 18 studies analyzed more than one drug class. Different assumptions for the dosage were used. In seven studies, switching within therapeutic classes was allowed. Three studies allowed stockpiling, nine studies censored hospital stays, and four studies censored death. Seventeen studies dichotomized the results, applying the cutoff ≥ 0.8 to define a patient as adherent. Eight studies analyzed adherence as a continuous value. The reporting quality of the methodology applied varied widely between studies. A gold standard is currently not available for the quantification of medication adherence in patients with chronic heart failure via claims data. To assess the methodology, the following parameters should be described: method of measurements, observation period, substances, dosing, switches, stockpiling, truncations, statistical analysis, and cutoff for adherence.

Agreement and validity of electronic health record prescribing data relative to pharmacy claims data: A validation study from a US electronic health record database.

BACKGROUND: Granular clinical and laboratory data available in electronic health record (EHR) databases provide researchers the opportunity to conduct investigations that would not be possible in insurance claims databases; however, for pharmacoepidemiology studies, accurate classification of medication exposure is critical. OBJECTIVE: The aim of this study was to evaluate the validity of classifying medication exposure using EHR prescribing (EHR-Rx) data. METHODS: We conducted a retrospective cohort study among patients with linked claims and EHR data in OptumLabs™ Data Warehouse. The agreement between EHR-Rx data and pharmacy claims (PC-Rx) data (for 40 medications) was determined using the positive predictive value (PPV) and medication possession ratio (MPR)-calculated in 1- and 12-month medication exposure periods (MEPs). Secondary analyses were restricted to incident vs prevalent EHR-Rxs, age ≥65 vs <65, white vs black race, males vs females, and number of EHR-Rxs. RESULTS: The validity metrics varied substantially among the 40 medications assessed. Across all medications, the period PPV and MPR were 62% and 63% in the 1-month MEP. They were 78% and 43% in the 12-month MEP. Overall, PPV and MPR were higher for patients with a prevalent EHR-Rx and age <65. CONCLUSIONS: Despite substantial variability among different medications, there was very good agreement between EHR-Rx data and PC-Rx data. To maximize the validity of classifying medication exposure with EHR prescribing data, researchers may consider using longer MEPs (eg, 12 months) and potentially require multiple EHR-Rxs to classify baseline medication exposure.