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.

Prescriber and pharmacy variation in patient adherence to five medication classes measured using implementation during persistent episodes.

PURPOSE: The objective of this study was to determine the fraction of variance in patient-level medication adherence accounted for by prescribers and pharmacies. METHODS: We used prescription drug claims paid between January 2010 and July 2011 to a national pharmacy benefits manager to define implementation during persistent episodes. Patients in Massachusetts or Rhode Island covered by Blue Cross Blue Shield of Rhode Island and their prescribers were included. Five drug classes were analyzed: angiotensin converting enzyme (ACE) inhibitors, antihyperglycemics (ANHGs), drugs for prostatic hyperplasia (PH), statins, and levothyroxine (THYR). We performed mixed models with random intercepts (drug, patient, prescriber, and pharmacy) and examined the fraction of variance explained at each level using intraclass correlations. RESULTS: Overall implementation ranged from 87 to 91%. The fraction of the explained variance in implementation to ACEs, ANHG, PH, statins, and THYR accounted for by prescribers was 16.4%, 12.6%, 14.6%, 15.6%, and 15% respectively; and for pharmacies 20.4%, 20%, 15.2%, 10.6%, and 9.4%, respectively. CONCLUSIONS: Prescriber and pharmacy effects accounted for a substantial amount of the explained variance in implementation across all five drug classes. Adherence interventions for chronic conditions that target prescribers and pharmacies, in addition to patients, could be effective and efficient. Copyright © 2016 John Wiley & Sons, Ltd.

Initial Medication Adherence-Review and Recommendations for Good Practices in Outcomes Research: An ISPOR Medication Adherence and Persistence Special Interest Group Report.

BACKGROUND: Positive associations between medication adherence and beneficial outcomes primarily come from studying filling/consumption behaviors after therapy initiation. Few studies have focused on what happens before initiation, the point from prescribing to dispensing of an initial prescription. OBJECTIVE: Our objective was to provide guidance and encourage high-quality research on the relationship between beneficial outcomes and initial medication adherence (IMA), the rate initially prescribed medication is dispensed. METHODS: Using generic adherence terms, an international research panel identified IMA publications from 1966 to 2014. Their data sources were classified as to whether the primary source reflected the perspective of a prescriber, patient, or pharmacist or a combined perspective. Terminology and methodological differences were documented among core (essential elements of presented and unpresented prescribing events and claimed and unclaimed dispensing events regardless of setting), supplemental (refined for accuracy), and contextual (setting-specific) design parameters. Recommendations were made to encourage and guide future research. RESULTS: The 45 IMA studies identified used multiple terms for IMA and operationalized measurements differently. Primary data sources reflecting a prescriber's and pharmacist's perspective potentially misclassified core parameters more often with shorter/nonexistent pre- and postperiods (1-14 days) than did a combined perspective. Only a few studies addressed supplemental issues, and minimal contextual information was provided. CONCLUSIONS: General recommendations are to use IMA as the standard nomenclature, rigorously identify all data sources, and delineate all design parameters. Specific methodological recommendations include providing convincing evidence that initial prescribing and dispensing events are identified, supplemental parameters incorporating perspective and substitution biases are addressed, and contextual parameters are included.

Revealed preference for community and mail service pharmacy.

OBJECTIVE: To determine revealed pharmacy preference and predictors among patients enrolled in a pharmacy benefit that offered a 90-day supply of prescriptions via mail service and community pharmacy channels, with no differences in out-of-pocket costs. DESIGN: Retrospective cohort study. SETTING: United States in 2008-09. PATIENTS: 324,968 commercially insured participants enrolled in plans that required use of mail service pharmacy for maintenance medications. INTERVENTION: Implementation of a pharmacy benefit design with optional use of either mail service or community pharmacy for 90-day supply prescriptions. MAIN OUTCOME MEASURES: Selection rates of mail service and community pharmacy and adjusted odds ratios for predicting community pharmacy for selected characteristics. RESULTS: In the first 4 months of the benefit design, 31.8% of participants previously mandated to use mail service pharmacy elected to fill 90-day prescriptions at community pharmacies. Selection of community pharmacy ranged from a low of 23.7% (previous mail service pharmacy users) to 66.3% (previous community pharmacy users). Among those initiating therapy, 44.3% selected community pharmacy for their new prescriptions, and among those with no previous mail use, 68% selected community pharmacy for new prescriptions. Preference for community/mail service pharmacy was dependent on numerous characteristics, including age, gender, household income, region, driving distance (time), and concomitant medication use. CONCLUSION: Patient behavior indicates that certain patients prefer to access prescription medications via mail service and others through community pharmacy channels. Restrictive benefit designs that incentivize patients to use less preferable pharmacy channels may adversely affect patient convenience, which could have the unintended consequence of reducing medication use and adherence.

Assessment of potential drug-drug interactions with a prescription claims database.

PURPOSE: The prevalence of 25 clinically important potential drug-drug interactions (DDIs) in a population represented by the drug claims database of a pharmacy benefit management company (PBM) was studied. METHODS: A retrospective cross-sectional analysis of pharmaceutical claims for almost 46 million participants in a PBM was conducted to determine the frequency of 25 DDIs previously identified as clinically important. A DDI was counted when drugs in potentially interacting combinations were dispensed within 30 days of each other during a 25-month period between April 2000 and June 2002. RESULTS: The number of DDIs ranged from 37 for pimozide and an azole antifungal to 127,684 for warfarin and a nonsteroidal antiinflammatory drug (NSAID). The highest prevalence (278.56 per 100,000 persons) and highest case-exposure rate (242.7 per 1,000 warfarin recipients) occurred with the warfarin-NSAID combination. The combination with the lowest overall prevalence (cyclosporine and a rifamycin, 0.10/100,000) differed from the combination with the lowest case-exposure rate (pimozide and an azole antifungal, 0.028 per 1,000 azole antifungal recipients). Number of cases, prevalence, and case-exposure rates for both sexes generally increased with age. An estimated 374,000 plan participants were exposed to a clinically important DDI during a 25-month period. Between 20% and 46% of prescription drug claims were reversed (canceled) for a medication with a drug interaction when a warning about the interaction was sent to the pharmacy. CONCLUSION: Analysis of prescription claims data from a major PBM found that 374,000 of 46 million plan participants had been exposed to a potential DDI of clinical importance.

Retrospective cohort study of diabetes mellitus and antipsychotic treatment in a geriatric population in the United States.

OBJECTIVES: The objective of this study was to investigate risk of diabetes among elderly patients during treatment with antipsychotic medications. DESIGN: We conducted a longitudinal, retrospective study assessing the incidence of new prescription claims for antihyperglycemic agents during antipsychotic therapy. SETTING: Prescription claims from the AdvancePCS claim database were followed for 6 to 9 months. PARTICIPANTS: Study participants consisted of patients in the United States aged 60+ and receiving antipsychotic monotherapy. The following cohorts were studied: an elderly reference population (no antipsychotics: n = 1,836,799), those receiving haloperidol (n = 6481) or thioridazine (n = 1658); all patients receiving any conventional antipsychotic monotherapy (n = 11,546), clozapine (n = 117), olanzapine (n = 5382), quetiapine (n = 1664), and risperidone (n = 12,244), and all patients receiving any atypical antipsychotic monotherapy (n = 19,407). MEASUREMENTS: We used Cox proportional hazards regression to determine the risk ratio of diabetes for antipsychotic cohorts relative to the reference population. Covariates included sex and exposure duration. RESULTS: New antihyperglycemic prescription rates were higher in each antipsychotic cohort than in the reference population. Overall rates were no different between atypical and conventional antipsychotic cohorts. Among individual antipsychotic cohorts, rates were highest among patients treated with thioridazine (95% confidence interval [CI], 3.1- 5.7), lowest with quetiapine (95% CI, 1.3-2.9), and intermediate with haloperidol, olanzapine, and risperidone. Among atypical cohorts, only risperidone users had a significantly higher risk (95% CI, 1.05-1.60; P = 0.016) than for haloperidol. Conclusions about clozapine were hampered by the low number of patients. CONCLUSION: These data suggest that diabetes risk is elevated among elderly patients receiving antipsychotic treatment. However, causality remains to be demonstrated. As a group, the risk for atypical antipsychotic users was not significantly different than for users of conventional antipsychotics.

Adherence to medication under mandatory and voluntary mail benefit designs.

OBJECTIVE: To compare adherence rates under voluntary and mandatory mail benefit designs. STUDY DESIGN: Matched retrospective cohort. METHODS: Adherence rates in the first year of therapy were compared between voluntary and mandatory mail cohorts composed of individuals who initiated statin, angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), platelet aggregation inhibitor, metformin, glitazone, or sulfonylurea therapy at a retail pharmacy between January 1 and March 31, 2009. Initiators in mandatory mail plans were matched on therapeutic class, age, sex, prospective risk, and cost of initial prescription with those in voluntary mail plans. Logistic regression models of optimal adherence were constructed to adjust for measured confounders. RESULTS: Persistence rates were similar through the first 60 days of therapy. The mandatory mail cohort had a notable drop in persistence by day 90 (63.3% vs 56.3%, P <.001), with a more pronounced drop among those without previous mail-service pharmacy use (50.5%). Median medication possession ratio (49.2% vs 57.4%) and optimal adherence (33.6% vs 36.1) were also lower. In the multivariable models, mandatory mail participants were less likely to achieve optimal adherence overall (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.67-0.74) and in the metformin (OR 0.55), sulfonylurea (OR 0.72), ACE inhibitor (OR 0.74), ARB (OR 0.69), and statin (OR 0.69) classes. Participants with no prior use of mail-service pharmacy had significantly lower odds of achieving optimal adherence in all therapeutic classes. CONCLUSIONS: Mandatory mail appears to cause some members to discontinue therapy prematurely, particularly those without previous mail service pharmacy experience.