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The American Journal of Managed Care February 2017
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Synchronized Prescription Refills and Medication Adherence: A Retrospective Claims Analysis
Jalpa A. Doshi, PhD; Raymond Lim, MA; Pengxiang Li, PhD; Peinie P. Young, PharmD, BCACP; Victor F. Lawnicki, PhD; Andrea B. Troxel, ScD; and Kevin G. Volpp, MD, PhD
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Cindy Reistroffer, DSc; Larry R. Hearld, PhD; and Jeff M. Szychowski, PhD
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Dori A. Cross, BSPH; Genna R. Cohen, PhD; Christy Harris Lemak, PhD; and Julia Adler-Milstein, PhD
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Aloke K. Mandal, MD, PhD; Gene K. Tagomori, BSc; Randell V. Felix, BSc; and Scott C. Howell, DO, MPH&TM
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Synchronized Prescription Refills and Medication Adherence: A Retrospective Claims Analysis

Jalpa A. Doshi, PhD; Raymond Lim, MA; Pengxiang Li, PhD; Peinie P. Young, PharmD, BCACP; Victor F. Lawnicki, PhD; Andrea B. Troxel, ScD; and Kevin G. Volpp, MD, PhD
A retrospective claims analysis showed that synchronized refill schedules were associated with better medication adherence among Medicare Advantage patients taking multiple maintenance medications.

Objectives: Medication adherence is often suboptimal, especially among patients on multiple chronic medications. We examined the association between synchronized medication refill schedules—which typically reduce organizational effort and logistical demands—and adherence.
Study Design: Retrospective study among patients enrolled in Medicare Advantage prescription drug plans. 
Methods: We used 2012 pharmacy, medical, and enrollment data linked with consumer meta-data for Medicare patients filling 2 or more maintenance prescriptions for antihypertensives, lipid-lowering agents, antidiabetic agents, antidepressants, and/or antiosteoporotic agents. Medication adherence for the year was measured using the proportion of days covered (PDC) at the drug class level. Patients were deemed adherent if drug class PDC was ≥0.80. Outcomes were compared between 1:1 propensity score-matched patients on synchronized versus nonsynchronized refill schedules for maintenance medications. 
Results: The synchronized refill group showed better adherence than the control group, although the magnitude of effects varied by drug class and specific outcome measure. Mean PDC scores ranged from 0.02 higher for antihypertensives to 0.07 higher for antidepressants in the synchronized refill group relative to the control group (P <.01). Further, compared with the control group, a larger proportion of synchronized refill group members were deemed adherent, ranging from 6 percentage points higher for antihypertensives to 15 percentage points higher for lipid-lowering agents (P <.01). Differences between the synchronized and control groups were larger among exclusive users of retail versus mail order pharmacies for maintenance medications.
Conclusions: Synchronized medication refill schedules were associated with better medication adherence, particularly for patients filling maintenance medications exclusively at retail pharmacies.

Am J Manag Care. 2017;23(2):98-104
Takeaway Points

Prescription synchronization programs are popular, but evidence regarding their utility in improving adherence is limited. Our retrospective claims analysis of Medicare Advantage patients receiving multiple maintenance medications (ie, antihypertensives, lipid-lowering drugs, antidiabetic agents, antidepressants, and/or antiosteoporotic agents) compared patients with synced refill schedules to propensity score-matched patients without synced schedules.
  • Compared with the nonsynced group, the synced group showed better adherence as measured by proportion of days covered. The magnitude varied by drug class.
  • Differences between the synced and nonsynced groups were larger in patients exclusively using retail pharmacies compared with patients exclusively using mail order pharmacies.
  • Synchronized prescription refills may facilitate adherence.
Poor medication adherence is a common problem among patients taking medications for a chronic condition.1 For patients receiving multiple medications for the treatment of more than 1 chronic condition, the resulting complexity can be particularly challenging.2 To address some of the practical burdens associated with long-term medication regimens, there has been increasing interest in whether synchronizing medication refill schedules—whereby all of a patient’s maintenance medications are refilled at the same time—may be a promising, scalable approach to improving adherence.

A recent review of the synchronization literature revealed few major peer-reviewed studies of synchronization.3 Holdford and Inocencio (2013) examined a convenience sample of patients at an independent retail pharmacy chain in the rural midwestern United States who were receiving new prescription medications, from 1 of 6 drug classes, to treat cardiovascular disease and diabetes.4 Intervention patients (ie, those who were participating in an appointment-based medication synchronization program that included synchronization of refills) had higher adherence across all drug classes than a control group of patients receiving usual care. A second study by Holdford (2015) among commercially insured retail pharmacy patients in Ohio who had been using medications for 6 months or more found similar results.5 Further, Choudhry et al (2011) used retrospective claims data from a large pharmacy benefit manager to examine therapeutic complexity in patients receiving refills for cardiovascular medications from a chain of retail and/or mail order pharmacies and found that less consolidated (ie, less synchronized) refill schedules were an independent predictor of worse medication adherence.2 Although valuable, the generalizability of these studies may be limited due to their focus on either specific geographic regions, retail pharmacy users, commercially insured patients, and/or a limited set of drug classes. 

Despite the absence of more generalizable evidence, there has been increasing adoption of medication synchronization programs across the nation.3 According to the American Pharmacists Association Foundation, more than 23 pharmacy chains and approximately 2000 independent pharmacies in the United States have implemented medication synchronization programs.6 An increasing number of states have proposed or recently passed legislation to remove barriers to medication synchronization, such as requiring insurers to pro-rate co-payments for the partial refills that are often needed to synchronize existing prescriptions.6 According to a recent national survey of 1000 adults 40 years or older who were receiving 1 or more medications for long-term medical conditions, about 1 in 8 patients were enrolled in a prescription synchronization program.7 In light of the growing adoption of, and policy interest in, synchronization programs, there is a pressing need for additional evaluations of the effectiveness of synchronizing refill schedules.

In this study, we utilized existing claims data for a sample of individuals enrolled in Medicare Advantage prescription drug plans (MA-PDs) who were receiving antihypertensives, lipid-lowering drugs, antidiabetic agents, antidepressants, and/or antiosteoporotic agents, to examine adherence outcomes in patients with synchronized medications compared with those whose medications were not synchronized. We focused on the Medicare population for several reasons. First, an estimated 85% of US adults 65 years or older have at least 1 chronic health condition, and 60% have at least 2.8 Second, given that forgetfulness and difficulties with transportation may increase with age, Medicare patients may be a particularly appropriate target population for interventions that reduce trips to the pharmacy and make it easier to manage prescription refills. Third, medication adherence for seniors has garnered increasing attention due to the CMS Five-Star Quality Ratings System program, which provides public ratings of Medicare Part D plans and ties performance to bonus payments.9 The ratings incorporate several medication adherence measures and award an increasing number of stars based on the percentage of a Part D plan’s members that meet adherence benchmarks.


Data Source and Sample Selection

Using 2012 pharmacy, medical, and enrollment data from Humana Inc’s top 50 (ie, highest enrollment) MA-PD plans linked with consumer meta-data files from the AmeriLINK Consumer Database,10 we took a 20% random sample of individuals meeting the following study criteria: 1) continuous eligibility for pharmacy and medical benefits in the same plan throughout 2012; 2) filling 2 or more prescriptions for antihypertensives, lipid-lowering drugs, antidiabetic agents, antidepressants, and/or antiosteoporotic agents; 3) a record of at least 2 different prescription fill dates for those medications in calendar year (CY) 2012; 4) exclusive use of either retail or mail order pharmacies to refill maintenance medications during the study year (ie, all prescriptions filled via 1 delivery channel); and 5) an equal number of unique maintenance drug classes in both the first half of the year and in the entire year (as a proxy for no major disruption in the maintenance drug regimen) to ensure that it would have been possible to  maintain synced refill schedules throughout the year.

The primary study group consisted of individuals who had a synchronized refill schedule for all of their maintenance medications for the entire study year—defined as having refills for all medications at every refill date during the year. For example, a patient taking 4 maintenance medications would need to show refills for all 4 medications at each refill date in order to be classified in the synchronized medication refill group.

In sensitivity analyses, we applied alternate eligibility criteria for the study group, representing less restrictive definitions of synchronization. In the first sensitivity analysis, patients were classified in the synchronized refill group if they refilled all maintenance drugs at the same time at the first 2 fills in the year (ie, started as synced, but did not necessarily remain synced). In the second sensitivity analysis, the synchronized refill group consisted of patients who refilled all maintenance drugs at once at any 2 consecutive fill dates during the year, regardless of when in the year this occurred.

The control group, which remained the same for all analyses, included patients who did not have any 2 consecutive fill dates during the year where they refilled all their maintenance drugs at the same time. The study protocol was approved by the University of Pennsylvania Institutional Review Board.


Our primary outcome was medication adherence at the drug class level, as measured by the proportion of days covered (PDC) for CY2012.11 In keeping with CMS’s technical guidance on measuring adherence to Star Rating medications, PDC was calculated as the proportion of days in the observation period (ie, 365 days in our study) with a day’s supply of a medication available from at least 1 prescription in that drug class.12 A continuous PDC measure was calculated for each of the 5 drug classes of interest among patients filling drugs for that class. We also created indicators for whether a PDC measure was ≥0.80, as this is a common cutoff for classifying a patient as adherent and also used by CMS for Part D Plan Star Ratings calculations.13

It should be noted that although some mail order pharmacies offer patients the option to receive automatic refills, CMS regulations require pharmacies to obtain consent from Medicare beneficiaries prior to shipping every refill. Thus, patients must take an action (eg, via initiating a refill order or responding to a call) before medication is sent. CMS has noted that this requirement would be expected to increase the value (ie, accuracy) of refill-related adherence measures.14

Statistical Analysis

We applied propensity score matching to balance the synchronized refill group members with control members across a variety of characteristics. As a first step, we stratified the sample by 4 key variables likely to affect medication adherence in order to ensure that matched pairs were identical with respect to the following parameters: 1) type of pharmacy where maintenance medications were filled (exclusive use of retail pharmacy vs exclusive use of mail order pharmacy); 2) insurance plan identifier, to account for differences in insurance benefits structure, co-payment requirements, drug formulary and utilization management tools, and other plan-specific features; 3) total number of maintenance medications; and 4) combination of maintenance drug classes being used (eg, a synchronized refill group member taking only antihypertensives and lipid-lowering medications would be matched to a control group member taking only those 2 classes of maintenance drugs).

Only strata with at least 1 synchronized refill group member and 1 potential control were considered in the matching algorithm. Within each stratum, we matched along a wide range of 310 variables, including: 1) sociodemographic variables (eg, age, gender, marital status, Medicare Part D low-income subsidy status, disability status, geographic region, county-level percent on Medicare Advantage); 2) Census tract-level measures for variables including home ownership, education, household income, and home value; 3) clinical variables (ie, medical condition indicators and the CMS Hierarchical Condition Categories (CMS-HCC) score)15; 4) prescription cost variables, including total prescription costs for the year, total prescription costs for maintenance medications only, and total out-of-pocket costs; and 5) consumer meta-data variables used to characterize plan members, including estimated income, interests, hobbies, consumer personas (eg, young urban singles, struggling seniors), occupation (including retirement status), attitudes (eg, positive outlook, control seekers), and tendency to drink alcohol and/or smoke. These variables were obtained from and/or predicted based on demographics, purchasing behavior, public records, Census data, consumer surveys, and other primary sources.

The success of propensity score matching was evaluated by comparing the means of matched synchronized and control group members along the 310 variables used. We calculated Cohen’s d to estimate the size of any differences between the matched groups across all variables; any sample characteristic with a Cohen’s d <0.10 was considered insignificant as per standard practice.16

Using the matched sample, we performed paired t tests for continuous outcomes and McNemar’s tests for categorical outcomes. We also conducted subgroup analyses by type of pharmacy used to fill all maintenance medications (exclusively retail vs exclusively mail order). We then tested—via regression analyses with interaction terms for the continuous PDC scores and Mantel-Haenszel tests for the dichotomous adherence measure (PDC ≥0.80)—whether the association between synchronized refills and medication adherence differed for exclusively mail order pharmacy users compared with exclusively retail pharmacy users.

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