Average Medication Possession Ratio Research Articles

SA38. Assessment of Cognitive Impairment, Treatment Adherence, and Healthcare Resource Utilization Among Treated Schizophrenia Patients

Background: Cognitive impairment associated with schizophrenia (CIAS) is common and can impact health outcomes (1). Information on the use of cognitive testing in clinical practice is lacking, and the relationship between cognitive impairment and healthcare resource utilization (HCRU) is poorly understood. This study assessed the measurement of CIAS and the association between CIAS, treatment adherence, and HCRU. Methods: Claims data from the Henry Ford Health System, a vertically integrated healthcare system serving metropolitan Detroit, Michigan, were used to identify patients aged 18 to 64 years with schizophrenia and use of antipsychotics from January 01, 2009, to June 30, 2014. Patients had ≥12 months of continuous enrollment preindex and ≥6 months postindex. The index date was the date of first diagnosis of schizophrenia. Patients with cognitive decline independent of CIAS or schizoaffective disorder were excluded. Electronic medical records (EMR) were used to confirm diagnosis of schizophrenia and to assess measures of CIAS. Due to the lack of standardized measures of CIAS, 2 independent expert reviewers assessed mental status exam (MSE) records for evidence of CIAS and classified patients as “clearly impaired” or “not impaired” during the assessment period. Administrative claims were used to assess treatment adherence during the study period and HCRU in the 12 months following index among patients with ≥12 months of follow-up. Descriptive statistics were performed as the study was exploratory in nature. Results: Following application of the inclusion/exclusion criteria and EMR assessment, 65 subjects were confirmed schizophrenia patients. The sample was 59% male with average age at index date of 43 years; 22% of patients were white, 62% black, and the remaining were unclassified. Only 8% of patients had evidence of a standardized cognitive assessment. However, all patients had ≥1 MSE records; 60% (N = 39) of patients were classified with CIAS through MSE review. The average medication possession ratio (MPR) for antipsychotic medications was 0.4 ± 0.3 for cognitively impaired patients (N = 29) and 0.6 ± 0.4 for nonimpaired patients (N = 25). CIAS patients had 0.5 ± 0.4 outpatient visits, 0.08 ± 0.0 hospitalizations, and 0.15 ± 0.08 emergency department visits per patient per month (PPPM), whereas nonimpaired patients had 0.7 ± 0.7, 0 ± 0.0, and 0.08 ± 0.0 visits, respectively. Conclusion: Although cognitive impairment is prevalent in schizophrenia patients, the results suggest that CIAS is not formally assessed in clinical practice. Additional research is needed to understand the relationship between CIAS, HCRU, and outcomes. Reference 1. Kitchen H, Rofail D, Heron L, et al. Cognitive impairment associated with schizophrenia: a review of the humanistic burden. Adv Ther 2012;29:148–62.

Treatment Patterns and Adherence Among Patients with Myelodysplastic Syndromes Receiving Deferasirox As Iron Chelation Therapy: A Real World Medicare Database Study

Background: Patients with myelodysplastic syndrome (MDS) may present with anemia and become red blood cell (RBC) transfusion dependent (TD), which increases the risk of iron overload (IO). Iron chelation therapy (ICT) treats IO and has been shown to be associated with improved survival and quality of life among TD MDS patients. Deferasirox (DFX) is an oral ICT used to reduce IO in TD MDS patients. This study aims to assess real-world treatment patterns and adherence among MDS patients on Medicare receiving DFX as ICT.Methods: This was a retrospective cohort study using 100% Medicare claims data from 2006-2013. Patients were diagnosed with MDS, identified using ICD-9 codes (238.72-238.76), and entered the study cohort when they met a minimum transfusion threshold of either: 10 consecutive weeks with at least 1 unit of RBC transfusion, or 20 total units of RBC transfusions. Treatment patterns, including discontinuation and treatment changes, were assessed among patients who received DFX as initial ICT and who had ≥180 days of follow-up. Discontinuation was defined as a minimum 45-day treatment gap. Adherence was defined as a medication possession ratio (MPR) ≥ 0.8. Treatment discontinuation, overall survival, acute myeloid leukemia (AML)-free survival, and cardiac event-free survival were compared between adherent and non-adherent patients using Kaplan Meier (KM) survival analysis, as well as Cox regressions controlling for time-dependent ICT use and baseline characteristics. Survivals were estimated as time from cohort entry to the event.Results: Among 6,796 MDS patients who met the minimum transfusion threshold, 591 (8.7%) received ICT. Median weeks of ICT was 15.14 (range=2.29 - 201.43 weeks). 583 (98.6%) initiated with DFX, and 374 DFX patients had a follow-up period of ≥180 days. Of these 374 patients, 213 (57.0%) discontinued DFX treatment within 180 days of initiation. Among the remaining 161 patients, one switched to deferoxamine (DFO), none augmented treatment with DFO, and 160 continued on DFX. The KM-estimated 3-month and 1-year DFX discontinuation rates were 36.5% and 77.4%, respectively, and the average time to discontinuation was 84.4 [Standard Deviation [SD]=48.6] days. Overall, the average 6-month MPR was 0.69 (SD=0.30), and 49.1% of patients were adherent (MPR≥0.8). Adherent patients had similar baseline characteristics compared with non-adherent patients, except that a lower proportion had renal disease (24.2% vs. 38.3%, P<0.01). Patients adherent to DFX had a lower risk of therapy discontinuation (Hazard Ratio=0.07, 95% Confidence Interval, 0.05-0.11) compared with non-adherent patients. Additionally, adherent patients had significantly longer cardiac event-free survival compared with non-adherent patients (1-year rate for cardiac-event/death: 66.1% vs. 76.1%, respectively, P<0.01). There were no statistically significant differences in overall survival and AML-free survival between adherent and non-adherent cohorts. Overall and AML-free survival were longer in the adherent cohort, however this did not reach statistical significance.Conclusions: DFX was the most commonly used ICT among eligible MDS patients. The majority of patients discontinued DFX within 1 year. Adherence to DFX was associated with statistically significant improved cardiac-event free survival. Further analysis on the long-term impact of the duration of chelation is warranted. DisclosuresFu:Novartis Pharmaceuticals Corporation: Consultancy. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Coe:Novartis Pharmaceuticals Corporation: Employment. Qiu:Novartis Pharmaceutical Corp: Employment, Equity Ownership. Li:Novartis Pharmaceuticals Corporation: Consultancy. Hanna:Novartis Pharmaceuticals Corporation: Consultancy. Tang:Novartis Pharmaceuticals Corporation: Consultancy. Elliott:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Paley:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership.

Medication adherence and persistence according to different antihypertensive drug classes: A retrospective cohort study of 255,500 patients

BackgroundSuboptimal adherence to antihypertensives leads to adverse clinical outcomes. This study aims to determine and compare medication adherence and persistence to different first-line antihypertensive drug classes in a large cohort. MethodsA cohort study was performed using claims data for prescriptions in the German statutory health insurance scheme that insures approximately 90% of the population. A total of 255,500 patients with a first prescription of an antihypertensive were included and followed for 24months. Persistence was determined based on gaps in continuous dispensation. Adherence was analyzed by calculating the medication possession ratio (MPR). ResultsWithin a 2-year period, 79.3% of all incident users of antihypertensive monotherapy met the classification of non-persistence (gap >0.5 times the number of days supplied with medication) and 56.3% of non-adherence (MPR<0.8). Beta-blockers (42.5%) and angiotensin-converting enzyme inhibitors (31.9%) were the most widely prescribed drug classes. Non-persistence and non-adherence were highest for diuretics (85.4%, n=6149 and 66.3%, n=4774) and lowest for beta-blockers (77.6%, n=76,729 and 55.2%, n=54,559). The first gap of antihypertensive medication occurred in median 160–250days after initiation, and the average medication possession ratio for all drug classes was less than 0.8. Fixed combinations with diuretics showed a 19.8% lower chance for non-adherence (OR=0.802, 99.9% CI=[0.715–0.900], p<0.001) and an 8.4% lower hazard for non-persistence (HR 0.916, 99.9% CI=[0.863–0.973], p<0.001) compared with monotherapies. ConclusionsThis large cohort study reveals important differences in 2-year adherence and persistence between antihypertensives that were lowest for diuretics. Fixed-dose combinations with diuretics may facilitate adherence compared to single substance products. However, effective strategies to improve adherence to antihypertensives are needed regardless of drug class.

Factors Associated with Adherence Rates for Oral and Intravenous Anticancer Therapy in Commercially Insured Patients with Metastatic Colon Cancer.

Over the past decade, oncology therapies have trended toward orally administered regimens, and there has been growing attention on evaluation of factors that affect adherence. There has not been a rigorous investigation of factors associated with adherence to intravenous (i.v.) and oral anticancer drugs in the setting of metastatic colorectal cancer (mCRC). To (a) assess potential patient-specific factors related to adherence to mCRC chemotherapy regimens and (b) compare adherence with IV versus oral dosage forms. A retrospective analysis was performed using the Optum Oncology Management claims database. Patients aged 18 years and older diagnosed with mCRC between July 1, 2004, and December 31, 2010, who were insured by a commercial health plan were included in the study. Adherence to i.v. and oral chemotherapy regimens was assessed using the National Comprehensive Cancer Network (NCCN) guidelines as the standard for expected cycle/regimen duration. The most commonly prescribed chemotherapy regimens were assessed. Adherence was evaluated using the medication possession ratio (MPR), calculated as the number of days a patient was covered by their chemotherapy regimen, according to NCCN guidelines, divided by the number of days elapsed from the first to the last infusion of that regimen. For most analyses, the MPR was considered a continuous variable that could take on values between 0 and 1. In other analyses, a dichotomous categorical variable designated if the MPR was at least 0.8 versus less than 0.8. The Wilcoxon rank sum, Kruskal-Wallis, and Student's t-test were used to detect differences in continuous measures between patients receiving oral capecitabine therapy versus i.v. chemotherapy. The chi square test (X(2) test) or Fisher's exact test was used to assess differences in the dichotomous MPR variable. Generalized estimating equation (GEE) models were used for regimen-level analyses to account for correlated responses within individuals. A total of 6,780 patients were included in the analysis, virtually all (98%) with commercial insurance coverage and the remaining (2%) with Medicare Advantage. Patients with mCRC received 17,095 regimens of chemotherapy, including 2,252 regimens of oral capecitabine. Of the 17,095 regimens, 6,780 (40%) were first-line regimens (i.e., the first time mCRC was treated for a given patient). The most common chemotherapy regimen, regardless of line of therapy, was FOLFOX (2,991 regimens, 17.5% of all regimens used). FOLFOX-based therapies with or without bevacizumab were the most common regimens for first- and second-line chemotherapy, while oral capecitabine treatment was the most commonly prescribed regimen for patients in third- or fourth-line therapy. Overall, medication adherence across all regimens was relatively high, with a mean MPR of 0.87 (SD = 0.17). Evaluation of the distribution of i.v. and oral capecitabine regimens revealed that 28% of all regimens were associated with an MPR of less than 0.8. The average MPR was clinically similar, but statistically higher for i.v. chemotherapy regimens (0.881) compared with oral capecitabine regimens (0.799; P < 0.0001). In the multivariable GEE model, lung or liver metastases were associated with a higher MPR, while lower Charlson Comorbidity Index and oral anticancer therapy were associated with lower MPR. Furthermore, as line of therapy increased, the difference in MPR between patients receiving oral capecitabine and i.v. chemotherapy increased. This analysis determined that adherence with i.v. chemotherapy regimens was clinically similar, but statistically higher, compared to oral capecitabine therapy. The difference in adherence rates between the 2 routes of administration increased as the line of anticancer regimen increased. These results suggest that there should be an increased focus on improving adherence rates in patients receiving oral capecitabine.

Impact of Employer-Sponsored Onsite Pharmacy and Condition Management Programs on Medication Adherence.

Poor medication adherence is associated with worsened health outcomes and higher health care expenditures. An increasing number of employers are sponsoring wellness initiatives designed to support healthy lifestyles, improve productivity, and offer a return on investment. Onsite pharmacies may facilitate higher medication adherence rates by providing employees a convenient, low-cost option for filling prescriptions that is integrated with other onsite health services. To (a) assess the impact of an employer's onsite pharmacy on health plan members' medication adherence using multiple measures of medication adherence and persistence, including medication possession ratio (MPR), average number of days until discontinuation (60-day gap in coverage), and percentage of members without a 30-day gap in coverage, and (b) evaluate these outcomes between those members who participated in condition management programs and those who did not. A retrospective analysis of a self-insured employer's claims data was undertaken. Medication adherence was assessed among the self-insured employer's health plan members, which included subscribers and their dependents who filled an asthma, depression, diabetes, hypertension, or hyperlipidemia medication at an onsite pharmacy, compared with those who used a community pharmacy. Multiple standard measures of medication adherence were considered. These measures included MPR, which was assessed for 1- and 2-year time periods. MPR was chosen because it is one of the most commonly referenced formulas in the literature and represents adherence over a fixed period of time. In addition, medication persistence was estimated by 30-day gaps in coverage and discontinuation of treatment. To assess the impact of onsite pharmacy use and account for covariate effects, the linear mixed model approach was applied with the logit transformed MPR as the response variable. An analysis of MPR among condition management participants was also performed. In total, 2,498 subscribers and their dependents were included in the analysis. The average MPR at 365 days was significantly higher (P < 0.0001) among onsite pharmacy users for all medication types, ranging from 13% higher for depression medications to 20% higher for hypertension medications. This trend persisted at 730 days (P < 0.001), with average MPRs ranging from 6% higher for hyperlipidemia medications to 11% higher for hypertension medications. A mixed model analysis indicated that members who used the onsite pharmacy were 3.44 times more likely to demonstrate medication adherence (95% CI = 2.84-4.16; P < 0.0001) at 365 days. Likewise, at 180 and 365 days, onsite pharmacy users were less likely to have 30-day gaps in treatment. The average number of days until discontinuation (defined as a 60-day gap) was also significantly longer (P < 0.0001) among onsite pharmacy users, ranging from an average of 56 additional days for depression medications to 105 additional days for hypertension medications. While the average MPR tended to be higher among those subscribers and their dependents who participated in condition management programs, this trend was not statistically significant for all medication types. Based on multiple measures, onsite pharmacy use was associated with higher medication adherence, while the results were inconclusive for condition management participation.

Meta-analysis of studies examining medication adherence, persistence, and discontinuation of oral antihyperglycemic agents in type 2 diabetes

Objective:To estimate overall rates of adherence, persistence, and discontinuation for patients with type 2 diabetes mellitus (T2DM) prescribed oral antihyperglycemic agents (OAHAs) by combining results of published studies.Research design and methods:A systematic literature review was conducted to identify articles published in English over the last 10 years evaluating the use of OAHAs for the treatment of T2DM. Databases searched included PubMed/MEDLINE, EMBASE, and the Cochrane Library. Seventy studies reporting adherence, persistence or discontinuation were identified by two independent reviewers and 40 reported relevant endpoints for the analysis. Outcomes included: (1) mean adherence defined as the average medication possession ratio (MPR); (2) proportion of adherent patients (MPR ≥ 80%); (3) discontinuation; and (4) persistence. Adherence and persistence were reported in observational studies only. Discontinuation was examined separately in randomized controlled trials (RCTs) and observational studies. Meta-analyses were conducted using both fixed and random effects models. When meta-analysis was not appropriate for a given outcome, descriptive statistics were provided.Results:The pooled mean MPR (95% confidence interval [CI]) was 75.3% (68.8%–81.7%; n = 13) and the proportion of adherent patients (95% CI) was 67.9% (59.6%–76.3%; n = 12). The discontinuation rate (95% CI) in RCTs was 31.8% (17.0%–46.7%; n = 7). Persistence and discontinuation were not assessed via meta-analysis for observational studies due to the limited number of available studies and differences in outcome definitions. In these studies, persistence estimates ranged from 41.0% to 81.1%, with a mean (95% CI) of 56.2% (46.1%–66.3%; n = 6), while discontinuation estimates ranged from 9.9% to 60.1%, with a mean (95% CI) of 31.4% (17.6%–45.3%; n = 6).Limitations:Limitations include (1) the use of MPR as a proxy for adherence, (2) limited number of studies available, and (3) observed heterogeneity.Conclusion:The results of the analysis demonstrate that medication adherence, persistence, and discontinuation rates are suboptimal in patients with T2DM prescribed OAHAs.

A retrospective descriptive analysis of patient adherence to dabigatran at a large academic medical center.

Clinical trials evaluating the efficacy of dabigatran followed a very strict protocol, which included close monitoring and follow-up. Patients followed in this controlled environment had an average medication possession ratio (MPR) greater than 0.95. However, very few studies have evaluated patient adherence to dabigatran in a real-world setting. Other studies of chronic medications indicate patients are not reliably adherent to twice daily regimens. Adherence to therapy is particularly important for direct thrombin inhibitors because there may be a risk of increased thromboembolic events associated with poor adherence to these agents. To identify the MPR for patients prescribed dabigatran at a large academic medical center and affiliated clinics. This retrospective descriptive study evaluated the MPR for patients prescribed dabigatran between January 1, 2012, and December 31, 2012. Patients included in this study had to receive dabigatran for a minimum of 3 months, have a primary care physician or cardiologist at the medical center or affiliated clinics, and must not use a mail order pharmacy. Patient MPR was calculated based on prescriptions picked up from the patient. After screening 400 patients, 159 patients met eligibility criteria. The mean MPR for the patients in this study was 0.63. Overall, 43% of the patients had an MPR of less than 0.80, and the mean MPR for this subgroup was 0.39 ± 0.27; 57% of the study population had an MPR of 0.80 or higher, with a mean MPR of 0.94 ± 0.08. There was a significantly higher proportion of men (67.7%, P = 0.0112) and a larger number of "as needed medications" prescribed (1.73 vs. 0.86, P = 0.0039) in patients with an MPR less than 0.80. There were 5 patients hospitalized during the study period (3 for bleeding, 1 for confusion, and 1 death not related to dabigatran therapy). The relatively low mean MPR seen in this study may indicate that there is a need for improved anticoagulation services and follow-up for patients taking dabigatran.

Associations between statin adherence level, health care costs, and utilization.

Evidence of the associations between statin adherence level, health care costs, and utilization is still limited. It is not clear whether better clinical outcomes derived from increasing statin adherence levels can be translated into cost savings and lower health care utilization. To evaluate the associations between statin adherence level, health care costs, hospital admission, and emergency room (ER) visits after statin therapy is taken for 1 year. A retrospective cohort study was performed to examine whether higher statin adherence level, measured as medication possession ratio (MPR), is associated with lower health care costs and hospital admission rate and with fewer ER visits. The study sample consisted of adult patients aged 18-64 years on an index date with continuous enrollment 12 months prior to and 12 months after the index date (the first fill date of a statin between January 1, 2009, and December 31, 2010). Study subjects also needed to have a minimum of 2 ICD-9-CM diagnoses for hyperlipidemia or diabetes in the pre-index date period. Main data sources were medical and prescription (Rx) claims, as well as enrollment files provided by a health benefit program and a medical carrier of state government and public school employees in a midwestern state. Study subjects were stratified into 8 groups based on statin MPR level: less than 40%, 40%-59%, 60%-69%, 70%-79%, 80%-84%, 85%-89%, 90%-95%, and 96%-100%. Total medical and Rx costs, as well as all-cause hospital admission rates and ER visits in a year after the index date, were computed based on medical and Rx claims. A separate breakout of statin costs, part of total Rx costs, was also computed. Generalized linear models (GLMs) were developed to test the hypothesis that higher statin adherence levels are associated with lower health care costs and utilization. A total of 10,312 subjects met the criteria and were selected. The average statin MPR in a year after the index date was 71.95%. Mean total costs (medical + Rx) in a year after the index date were $6,064.36. There were significant variations in Rx costs and total health care costs as well as ER visits among the 8 patient groups stratified using the statin MPR level. A GLM model showed that all the ratios of health care costs among groups with statin MPR from 40%-59%, 60%-69%, 80%-84%, 85%-89%, 90%-95%, and 96%-100% were larger than 1 and statistically significant compared with the reference group with statin MPR less than 40%, suggesting those groups had higher health care costs than the reference group with the lowest statin MPR level. Based on a logistic regression model of hospital utilization for this study population, all the odds ratios of all-cause hospitalization among the groups with higher statin MPR were not statistically significant, suggesting that the likelihood of hospitalization for patients with higher statin MPR was not statistically lower than that of the reference group with statin MPR less than 40%. After controlling for all other covariates, another GLM model based on the Poisson distribution and log link function showed that ratios of ER visits among groups with statin MPR from 60%-69%, 80%-84%, 85%-89%, 90%-95%, and 96%-100% were smaller than 1 and statistically significant, suggesting the groups had fewer ER visits than the reference group with statin MPR less than 40%. The patient group with statin MPR from 96%-100% was estimated to have the lowest number of ER visits. Our study results show that much higher statin adherence levels are related to fewer ER visits after statin treatment is taken for a year among beneficiaries; however, the study is inconclusive whether higher statin adherence levels are associated with lower overall health care costs in a year after statin therapy is taken. Further research is needed to evaluate the associations between statin adherence level, the cost of cardiovascular care alone, and utilization over a longer period.

A 36 month naturalistic retrospective study of clinic-treated youth with attention-deficit/hyperactivity disorder.

The purpose of this study was to investigate factors for pharmacotherapy adherence in patients with attention-deficit/hyperactivity disorder (ADHD), with an emphasis on medication possession ratio (MPR). The medical records of 300 clinic-treated youth diagnosed with ADHD were retrospectively reviewed. Patients from March 2005 through January 2009 were diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, 4(th) ed., Text Revision (DSM-IV-TR) and psychological tests. Patients were classified based on the time period from the initial visit to the last visit. We selectively compared the early dropout group within 6 months and the long-term medication group over 36 months (LMed) to identify long-term follow-up characteristics. The short-term follow-up group was divided into an early dropout group without pharmacotherapy commencement (EDO) and a short-term medication group (SMed). Sociodemographic data, psychological test scores, and average MPR of the EDO, SMed, and LMed groups were compared. The number of EDO patients was 69 (23.0%) out of the 300 total patients who were studied, and there were 59 SMed patients (19.3%), and 60 LMed patients (20.0%). Compared with other groups, the EDO group included significantly more younger patients, younger parents, higher maternal education level, lower Short Form Korean-Conners' Parent Rating Scale (K-CPRS) score, and higher full scale and performance intelligence quotient (IQ). There was no significant correlation between the average MPR and the treatment duration. Within the first 6 months of visiting the hospital, >40% of the patients dropped out of treatment regardless of methylphenidate (MPH) use. Twenty percent of the subjects showed adherence to MPH medication after 36 months.

Association between regular molecular monitoring and tyrosine kinase inhibitor therapy adherence in chronic myelogenous leukemia in the chronic phase

Objective:Adherence with oral tyrosine kinase inhibitor (TKI) therapy over prolonged timeframes is required for successful outcomes among patients with chronic phase chronic myelogenous leukemia (CP-CML). Since quantitative polymerase chain reaction (qPCR) monitoring may identify early suboptimal responses, and thereby permit detection of non-adherence to therapy, we sought to assess the association between frequency of molecular monitoring and medication adherence.Research design and methods:This is a retrospective cohort study design of diagnosed CP-CML obtained from two large US administrative claims databases. Patients were grouped into cohorts based on the number of qPCR tests they had. Adherence was assessed both by medication possession ratio (MPR) and proportion of days covered (PDC) and was compared between qPCR cohorts. A sensitivity analysis was performed by adjusting for the number of oncology outpatient visits not due to routine molecular monitoring.Results:Over the 12 month study period, 1205 CML patients met the selection criteria; 41.0% had no qPCR tests, 31.9% had 1–2 tests, and 27.1% had 3–4 tests; 88.9% of patients were initiated on imatinib. Patients in the 3–4 qPCR tests cohort had an average MPR that was 10.22 (p < 0.001) and 9.54 (p < 0.001) percentage points higher compared to patients in the 0 tests cohort and the 1–2 tests cohort. When using PDC as a measure of adherence, similar results were obtained. The results of the sensitivity analysis were consistent with core analysis findings, excluding number of physician visits as a potential driver of adherence.Limitations:These findings demonstrate an association, not causation, between molecular monitoring frequency and adherence.Conclusions:Frequent molecular monitoring (3–4 times per year as recommended in current guidelines) is associated with greater TKI treatment adherence for patients diagnosed with CML. Since TKI adherence >80% has been associated with better clinical outcomes, this study underscores the importance of molecular monitoring.

A method for calculating adherence to polypharmacy from dispensing data records

Background Several measures for calculating adherence to one medication from dispensing data records have been proposed, but the nomenclature is inconsistent and computations vary. The same measures, like the medication possession ratio (MPR), have been used for multiple medication regimens, and have tended to over- or under-estimate adherence rates. Objective To demonstrate the impact of varying elements in MPR to a single medication regimen; to define standards for the estimation of adherence to polypharmacy; to propose a new method for calculating adherence to polypharmacy; to face validate it. Setting Face validity of the proposed method. Method Variations in the MPR formula were simulated. Standards for the estimation of adherence to polypharmacy were defined. A new method to calculate adherence to polypharmacy was established. Its face validity with three illustrative cases obtained from a pharmacy refill database was assessed. Main outcome measure Adherence rate to polypharmacy from refill data records. Results MPR to a single medication is operationalized in the numerator and denominator and is influenced by the parameters like observation period, medication gaps, overlap. For polypharmacy, an average MPR is commonly used, which is not accounting for the specificity of multiple medications, and hence overestimating adherence rate. We propose the daily polypharmacy possession ratio (DPPR) as an index of adherence to polypharmacy. It estimates the proportion of time a patient had medication available for use by considering the presence or absence of multiple medications on each day in the observation period. We calculated possession rates from refill histories over 31 months (January 1, 2011–July 31, 2013) for three illustrative patients. The average MPR estimates were 80 % for a patient with 6 medications/20 refill dates, 90 % for a patient with 4 medications/11 refill dates, and 89 % for a patient with 3 medications/17 refill dates. The corresponding DPPRs were 75, 88 and 99 %, indicating overestimations by 5 and 2 %, and underestimation by 10 %, respectively. Conclusion The DPPR accounts for the specificity of polypharmacy including number of medications, medication switching, duplication, overlapping. Research is needed to further confirm the validity of this new index.

Compliance to fingolimod and other disease modifying treatments in multiple sclerosis patients, a retrospective cohort study

BackgroundAdherence to disease-modifying therapies (DMTs) results in the reduction of the number and severity of relapses and delays the progression of multiple sclerosis (MS). Patients with lower adherence rates experience more inpatient visits and higher MS-related medical costs. Fingolimod, the first oral DMT approved by the US Food and Drug Administration, may improve the access and compliance to MS treatment when compared to injectable DMTs.MethodsThis retrospective cohort study used pharmacy claims from Medco Health Solutions, Inc., of patients who initiated DMTs between October 2010 and February 2011. Initiation was defined as no prescription fills for the same DMT in the prior 12 months. Patients without a DMT prescription fill 12 months before the index date were considered naïve users. Compliance was measured via proportion of days covered (PDC) and medication possession ratio (MPR) for 12 months post-index. Discontinuation was defined as a ≥60-day gap of index DMT supply. Cox proportional hazard models compared time to discontinuation between cohorts.ResultsOf 1,891 MS patients (mean age: 45.7; female: 76.4%), 13.1% initiated fingolimod, 10.7% interferon beta-1b, 20.0% intramuscular interferon beta-1a, 18.8% subcutaneous interferon beta-1a, and 37.4% glatiramer acetate. Patients initiating fingolimod had highest average PDC and MPR in both experienced (fingolimod: mean PDC=0.83, 73.7% with PDC≥0.8; mean MPR=0.92, 90.5% with MPR≥0.8) and naïve DMT users (fingolimod: mean PDC=0.80, 66.7% with PDC≥0.8; mean MPR=0.90, 87.4% with MPR≥0.8). The proportion of patients discontinuing index DMT within 12 months was significantly lower for the fingolimod cohort (naïve: 31.3%; experienced: 25.7%). Adjusted results found that patients receiving self-injected DMTs discontinued significantly sooner than fingolimod users. This association was generally stronger in experienced DMT users.ConclusionsFingolimod initiators were more compliant, less likely to discontinue treatment, and discontinued later than patients who initiated self-injected DMT.

Ethnic Disparities in Adherence to Antihypertensive Medications of Medicare Part D Beneficiaries

To determine the level of adherence to medications and characteristics of Part D beneficiaries associated with higher levels of antihypertensive medication adherence. Retrospective cohort study. Medicare claims and Part D event files. Medicare Part D enrollees with prevalent uncomplicated hypertension who filled at least one antihypertensive prescription in 2006 and two prescriptions in 2007. Medication adherence was defined as an average medication possession ratio of 80% or greater. Potential factors associated with adherence evaluated were age, sex, race or ethnicity, socioeconomic factors, comorbidity, medication use, copayments, being in the coverage gap, and number of unique prescribers. Overall adherence was 79.5% of 168,522 Medicare Part D enrollees with prevalent uncomplicated hypertension receiving antihypertensive medicines in 2007. In univariate analysis, adherence varied significantly according to most patient factors. In multivariable analysis, lower odds of adherence persisted for blacks (odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.51-0.55), Hispanics (OR = 0.58, 95% CI = 0.55-0.61), and other non-white races (OR = 0.80 95% CI = 0.75-0.85) than for whites. Greater comorbidity and concurrent medication use were also associated with poorer adherence. Adherence was significantly different across several geographic regions. A number of associations were identified between patient factors and adherence to antihypertensive drugs, with significant differences in adherence according to ethnicity. Improving adherence could have significant public health implications and could improve outcomes specific to hypertension, as well as improving cost and healthcare utilization.

Associations Between Prescription Copayment Levels and β-Blocker Medication Adherence in Commercially Insured Heart Failure Patients 50 Years and Older

BackgroundHigh prescription copayments may create barriers to care, resulting in medication nonadherence. Although many studies have examined these associations in commercially insured patients with chronic disease, few have examined β-blocker effects in heart failure patients. ObjectiveAssociations between β-blocker prescription copayment levels and medication nonadherence were examined within commercially insured beneficiaries with a diagnosis of heart failure. MethodsHeart failure patients were identified as those with at least 1 inpatient claim or 2 outpatient claims with an associated International Classification of Diagnosis, 9th Edition (ICD-9) code of 428.x, in addition to those with at least 2 β-blocker claims. Copayment levels were defined in using $5.00 (USD) interval categories, and adherence was defined using the medication possession ratio (MPR). Ordinary least squares (OLS), fixed effects (FE), and random effect (RE) models were used to estimate associations between copayment level and MPR. Logistic regression was used to estimate the probability of nonadherence (MPR < 0.80) conditional upon copayment level. Regressions controlled for patient demographics, health status, prior hospitalizations, and concomitant medication use. ResultsThe highest β-blocker copayment level ($26+) had an average MPR that was 0.07 (95% CI, –0.11 to –0.03), 0.08 (95% CI, –0.12 to –0.04), and 0.09 (95% CI, –0.17 to –0.02) units lower than β-blocker copayment level ($0 to $1) in the OLS, RE, and FE models, respectively. Copayment levels $21–$25 and $26+ were significantly associated with an increased risk of medication nonadherence (OR = 1.64; 95% CI, 1.1–2.4; and OR = 2.5; 95%, CI 1.6–4, respectively). ConclusionsCommercially insured heart failure patients aged ≥50 years who are prescribed higher costing β-blockers may have up to an average 9% decrease in annual β-blocker medication supply as well as an increased risk of nonadherence (MPR <0.80). Results need to be interpreted with caution given the potential of selection bias due to selective prescribing. Associations between copayment levels and nonadherence need to be further explored given the adverse health consequences of nonadherence to β-blockers.

Adherence to treatment of primary osteoporosis and its association to fractures—the Swedish Adherence Register Analysis (SARA)

Osteoporosis treatments reduce the risk of fractures. The objective of this study was to investigate adherence to treatment of osteoporosis and its association to fractures in Sweden. Adherence to treatment of osteoporosis in Sweden is poor, and time on treatment was found to be significantly associated with fracture incidence. The objective of this study was to estimate persistence and compliance to treatment of primary osteoporosis in Sweden. A second aim was to investigate the determinants of non-persistence and the association between adherence and fracture incidence. Patients were identified through filled prescriptions for alendronate, risedronate, strontium ranelate, and raloxifene between 2005 and 2009 from the Swedish Prescribed Drug Register. Persistence was investigated using survival analysis. Medication possession ratio (MPR) was used to measure compliance in persistent patients. The outcome measure in the analysis of adherence and fracture incidence was hospitalized osteoporotic fractures. The final cohort consisted of 56,586 treatment-naïve patients (mean age 71, 86% women). A total of 51%, 35%, 25%, and 14% were still on treatment (switching allowed) after 1, 2, 3, and 4 years, respectively. Average MPR in persistent patients was 94.2% (CI(95) 94.2-94.3%). Compared with <1 month of therapy, treatment for 1 month to 1 year, 1 to 2 years, and 2 to 3 years was associated with a lower 3-year fracture incidence (HR 0.86, p = 0.091; HR 0.67, p < 0.001; and HR 0.59, p < 0.001, respectively). No significant relationship was identified between MPR and fracture risk. Persistence to treatment of osteoporosis in Sweden is poor and approximately 50% of all treatment-naïve patients discontinue therapy within 1 year. Average refill compliance, estimated only while the patients were persistent, was found to be close to perfect. A strong association was identified between treatment persistence and fracture incidence, which calls for action to improve the current situation.

Adherence and persistence with teriparatide among patients with commercial, Medicare, and Medicaid insurance

Adherence to, and persistence with, treatments for osteoporosis are low. Adherence with teriparatide decreases over time. Higher copayments in the commercial/Medicare population were associated with worse persistence. Understanding factors such as prior screening, prior treatment history, and out of pocket costs that influence persistence with teriparatide may help clinicians make informed decisions. The purpose of this study was to evaluate adherence and persistence with teriparatide. Beneficiaries with at least one claim for teriparatide in 2003 or 2004 and continuous enrollment in the previous 12 months and subsequent 6 months were identified in a national commercial/Medicare and Medicaid administrative claims database (MarketScan®). Adherence was assessed through calculation of the medication possession ratio (MPR). Persistence was measured by time until discontinuation and time until first 60-day gap in treatment. Factors associated with persistence were assessed using Cox proportional hazards models. The average MPR at 6 months was 0.74 (N=2,218) and at 12 months, was 0.66 (N=1,303). At 6 months, 64.6% of patients remained on therapy and at 12 months, 56.7% remained. Bone mineral density screening and use of antiresorptive therapy within the 12 months pre-period, and lower patient copayments were associated with increased persistence. Patients appear to have good adherence with teriparatide over the first 6 months which declines over time. Prior screening and treatment of osteoporosis and out of pocket costs appear to impact persistence. To optimize patient outcomes, clinicians should consider clinical factors that impact persistence, while healthcare decision makers should consider the negative effect of higher patient copayments on persistence.

우리나라 성인 2형 당뇨환자에서의 외래 투약 순응도와 관련요인 분석

Objectives : This study aims to estimate the oral antihyperglycemic medications adherence among ambulatory care with adult type 2 diabetes patients and to identify factors affecting the medication adherence in Korea. Methods : This study used the Korean National Health Insurance Database. Study population was 40,082 patients who were 20 years of age or older and first diagnosed with type 2 diabetes (ICD-10: E11) in 2004. The patients were followed up for two years in order to measure adherence with oral antihyperglycemic medications. The level of medication adherence was measured by the medication possession ratio (MPR). Results : The average MPR in the study population was 49.5%. The appropriate adherence rate (MPR80%) was 29.4% and showed variation according to the characteristics of individual patients. Multiple logistic regression analysis revealed that the odds of appropriate adherence increased with female (OR:1.21, CI:1.14-1.27), older age, increasing ambulatory care visits, health insurance (OR:1.53, CI:1.33-1.76), decreasing ambulatory care providers, using a specialized general hospital as their main attending medical institution (OR:10.08, CI:8.96-11.33), having co-morbidity, using polytherapy (OR:1.07, CI:1.01-1.13). Conclusions : The medications adherence for patient with type 2 diabetes is low in Korea, and shows variation according to the characteristics of patients. For proper management of diabetes, health care policy is expected to be enacted to improve medications adherence continuously. In particular, more intensive management is needed for patients with low medications adherence. Also, health care policy makers need to develop the program to induce health care utilization by a patient to be more concentrated with the same provider.

Low Treatment Adherence with Antipsychotics is Associated with Relapse in Psychotic Disorders within Six Months after Discharge

The aim of this study was to assess the association between treatment adherence with antipsychotics and schizophrenia relapse on a continuous scale. A cohort study with a total of 477 patients with schizophrenia who were recently discharged from an inpatient clinic was performed. In the 160 people who relapsed within the six months after discharge the average medication possession ratio was 0.50. This was 0.59 in the 317 persons who were not readmitted. The resulting hazard ratio for the medication possession ratio on relapse risk was 0.60 (95% confidence interval: 0.42-0.88). The found hazard ratio indicates that the risk of relapse is substantially decreased when a patient is properly adherent to the antipsychotic therapy that was prescribed at the inpatient clinic.

Impact of Adherence to Interferons in the Treatment of Multiple Sclerosis

Relapsing-remitting multiple sclerosis (RRMS) is a chronic disease affecting about 400 000 people in the US characterized by increasing patient disability and burden on society. While there is no cure for multiple sclerosis (MS), pharmaceutical treatments exist that can limit the number of relapses a patient experiences, and slow disease progression. One such class of agents used to treat RRMS are the interferons: interferon-beta-1a (Rebif and Avonex and interferon-beta-1b (Betaseron and Extavia). Patients must take these injectable medications regularly to achieve the optimal outcomes. However, patient issues and potential adverse effects of the medication may prevent the patient from taking the medication as directed and lower adherence. To date, limited evidence exists regarding the effect of patient adherence to interferon-beta therapies on clinical and economic outcomes. The purpose of this study was to explore the impact of patient adherence to interferon-beta therapy on MS relapse rates and healthcare resource utilization. Using a non-experimental, retrospective cohort design, a sample population (n = 1606) was drawn from patients identified in a database that includes both pharmacy and medical claims data. The study population was separated into two groups based on a measure of medication possession ratio (MPR)-adherent and non-adherent patients, and adherence was defined as MPR > or =85% in a given year during the study period (2006-8). Key outcome variables included MS relapses and healthcare resource utilization. Data were analysed using parametric and non-parametric statistics, and regression modeling. During the study period, the average MPR for all patients on interferon-beta therapy varied from 72% to 76%. Only 27-41% of patients in each year were considered adherent (i.e. MPR > or =85%) and only 4% of patients had an MPR of > or =85% throughout the 3-year study period (2006-8). Patients who were adherent tended to have a lower risk of relapses over 3 years than non-adherent patients. A significantly lower risk of relapses was found in 2006 (risk ratio [RR] 0.89; 95% CI 0.81, 0.97). Furthermore, an increasingly larger effect emerged between adherence and relapses when comparing adherent patients (MPR > or =85%) with subgroups of non-adherent patients (<80%, <75%, <70%, <65% and <60%). The impact of adherence on emergency room (ER) visits also tended to suggest a lower risk during 2006, 2007 and 2006-8. During 2008, the risk for an ER visit was significantly lower for patients adherent in 2007 (RR 0.78; 95% CI 0.61, 0.99). Inpatient admissions followed the ER trends, as patients considered adherent in 2006 and 2007 tended to have a lower risk over 3 years. This result was significant for patients adherent in 2007 (RR 0.79; 95% CI 0.65, 0.98). The findings of low patient adherence and the impact of adherence on relapses and healthcare resource utilization strongly suggest opportunities to reduce healthcare resource utilization and healthcare costs among RRMS patients taking interferon-beta therapy. Efforts should be undertaken to understand and improve medication-taking behaviour in this population so as to minimize the negative impacts of RRMS on patients while reducing unnecessary direct and indirect costs to treat disease exacerbations.

Add-back therapy use and its impact on LA persistence in patients with endometriosis

Objectives:Persistence and compliance in women with endometriosis who are receiving gonadotropin-releasing hormone agonists (GnRH-a) may be limited by its hypoestrogenic side effects. Use of concomitant therapy with norethindrone acetate (NA), estrogen, estrogen/progestin combinations, or other progestin (i.e., ‘add-back therapy’ [ABT]) is recommended to alleviate these side effects. This retrospective study evaluated ABT utilization and its effect on compliance and persistence in patients with endometriosis taking the GnRH-a leuprolide acetate (LA) depot suspension.Methods:A retrospective analysis of a large pharmacy claims database identified patients who started LA therapy from 2002 to 2004 for the treatment of endometriosis. Patients were identified as having received ABT if they started 7 days before, or within 45 days of the last LA fill.Results:A total of 1285 women with endometriosis who began using LA were identified with 12 months of evaluable data: 211 (16.4%) used concomitant NA therapy, 116 (9.0%) used concomitant estrogen-based therapy, 28 (2.2%) used concomitant combination estrogen- and progestin-based therapies, 56 (4.4%) used concomitant progestin-based therapy, and 874 (68.0%) did not use any ABT. Mean (±SD) LA persistence in women receiving NA-based ABT was 5.83 ± 2.98 months, compared with 4.25 ± 2.62 months for those not using ABT (P < 0.0001). Average medication possession ratio was 0.43 ± 0.20 for women receiving NA-based ABT versus 0.32 ± 0.18 for those not receiving any ABT (P < 0.0001). Patients < 30 years of age were most likely to continue therapy longer and have greater compliance compared with the older age group cohorts (P < 0.01). Patients who used ABT continued to do so for 3.79 ± 3.21 months.Limitations:Limitations of this study include those associated with the use of retrospective claims databases: It does not include any information regarding the patient’s pain symptoms, disease severity, or other factors, which could correlate to compliance and persistence.Conclusions:Among women using LA therapy for endometriosis, only 32% used any type of ABT, and these patients had significantly higher persistence and compliance with LA therapy compared to no ABT user group.