Jay Visaria, PhD, MPH

To evaluate whether adults enrolled in commercial health insurance plans that provide reimbursement for herpes zoster vaccine (HZV) and pneumococcal vaccine (PV) through the medical and pharmacy benefits have higher vaccination rates compared with those whose health plans cover vaccines under the medical benefit alone. 

Retrospective claims analysis using medical and pharmacy claims data from January 1, 2012, through December 31, 2014. Separate but parallel analyses were conducted for HZV and PV. 

Previously unvaccinated patients were divided into exposed (those in employer groups with both medical and pharmacy benefits for vaccinations) and unexposed (those in employer groups that covered vaccination under the medical benefit only) cohorts. 

For HZV, 32,506 and 1299 patients received vaccinations in the exposed and unexposed cohorts, respectively. The vaccination rate was significantly higher in the exposed (42 vaccinations per 1000 eligible person-years) than the unexposed cohort (15 vaccinations per 1000 eligible person-years; 

<.001). For PV, 16,409 and 1386 received vaccinations in the exposed and unexposed cohorts, respectively. The vaccination rate was significantly higher in the exposed (22 vaccinations per 1000 eligible person-years) than the unexposed cohort (17 vaccinations per 1000 eligible person-years; 

Among members with commercial health insurance, HZV and PV rates were significantly higher among those whose insurance covered vaccinations under both medical and pharmacy benefits, compared with members whose insurance covered vaccines under the medical benefit only. Pharmacy-based vaccination coverage from commercial health insurance plans may help improve adult vaccination rates. 

Am J Manag Care. 2018;24(Spec Issue No. 8):SP286-SP293

Covering herpes zoster and pneumococcal vaccinations under both the medical and pharmacy health insurance benefit results in significantly higher vaccination rates among those with commercial health insurance, compared with health plans covering the vaccines under the medical benefit only.

 Covering vaccines under the medical benefit limits vaccine administration to physician offices, whereas allowing coverage under the pharmacy benefit expands administration to pharmacies.

Pharmacy-based vaccination may help improve adult vaccination rates, which remain below Healthy People 2020 targets.

Pneumococcal pneumonia and herpes zoster are vaccine-preventable diseases, but they continue to cause considerable burden among older adults.

 The herpes zoster vaccine (HZV) and 2 pneumococcal vaccines (PVs), the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23),

 effectively reduce the incidence of these diseases. However, despite clinical recommendations for their use, adult vaccination rates are persistently low, especially in at-risk populations, such as those with compromised immune systems.

Barriers to adult vaccination are numerous and vary according to an individual’s age, health status, life situation, and ethnicity,

but they generally fall into 3 categories: lack of healthcare provider recommendation

; lack of knowledge about vaccine effectiveness or seriousness of the disease

; and vaccine costs, not only the cost to the patient but also the providers’ costs for purchasing and administering vaccines.

 Patient mistrust of vaccines, of the healthcare system in general, or of recommendations backed by government entities present barriers for some individuals.

 Additionally, adult healthcare largely focuses on acute or chronic rather than preventive care, with patients seeing both generalists and specialists, making coordination of adult vaccination difficult.

 The CDC’s Healthy People 2020 goals include increasing the rates of PV receipt among adults 65 years or older to 90% and of HZV receipt among adults 60 years or older to 30%.

 Proposed interventions to help meet these vaccination goals include increasing provider awareness, to consequently improve communications to patients about necessary vaccines and understand patient barriers to vaccination; establishing national leadership to coordinate adult vaccination efforts; and improving appropriate financial and infrastructure resources.

Infrastructure improvement includes increasing the use of pharmacies to provide adult vaccinations,

 which can circumvent office-based barriers to vaccination. For example, whereas physician offices most often require appointments, pharmacies offer walk-up service, multiple locations, and extended business hours, allowing for vaccinations during evenings or weekends.

 Additionally, outreach by pharmacists, including advertising vaccination services, draws in customers who may have otherwise not considered vaccination.

 Vaccination costs have been shown to be up to 25% lower in some pharmacies than in physician offices.

 The advantages of pharmacy-administered vaccination can be an important factor in achieving the Healthy People 2020 vaccination goals of 90% for PV and 30% for HZV.

Vaccines traditionally have been administered in physician offices and billed under the medical health insurance benefit, but covering vaccines under the pharmacy benefit may improve adult vaccination rates because pharmacies already are reimbursed through the pharmacy benefit.

 The increased availability of vaccination in nontraditional settings offers an opportunity to evaluate whether the coverage of vaccination through both medical and pharmacy benefits can help increase rates of HZV and PV receipt among adults. Therefore, the objective of this study was to evaluate whether adults enrolled in commercial health insurance plans that provide reimbursement for PV and HZV through the medical and pharmacy benefits have higher vaccination rates compared with those whose health plans cover vaccines under the medical benefit alone.

This retrospective cohort study used medical and pharmacy claims data from January 1, 2012, to December 31, 2014 (the study period). Data were obtained from the HealthCore Integrated Research Database, which contains longitudinal claims data for 48.9 million members across 14 health plans geographically dispersed across the United States. Researchers accessed only a limited dataset in full compliance with relevant provisions of the Health Insurance Portability and Accountability Act of 1996.

Separate but parallel analyses were conducted for HZV and PV receipt rates. The analysis included health plan members enrolled in employer groups (ie, a group of beneficiaries who had a set of common medical and pharmacy benefits) that fell into 1 of 2 categories. The first category was employer groups with pharmacy benefit coverage for vaccination, encompassing those employer groups that covered HZV and PV under both medical and pharmacy benefits during the study period (the exposed cohort). The second category included employer groups with no pharmacy benefit coverage for vaccination—that is, those that covered vaccination under only the medical benefit during the study period (the unexposed cohort). In both categories, HZV and PV were offered at no out-of-pocket cost to enrollees.

The 2012 calendar year was used to establish baseline vaccine use and comorbidity profiles. Vaccination rates were measured during the 2013 and 2014 calendar years.

Commercially insured employer groups were selected based on exposure status determined by the presence of paid pharmacy claims for HZV, PV, or influenza vaccination during 2013 and 2014. Presence of paid claims indicated reimbursement. Pharmacy claims for influenza vaccination were used in addition to HZV and PV to identify employer groups with vaccine coverage in the pharmacy benefit because of the large proportion of enrolled members eligible for and receiving influenza vaccination (approximately 50% of members). Health plans that offered pharmacy benefit reimbursement for 1 of the vaccines (HZV, PV, or influenza) did so for all 3. To minimize the misclassification of exposed groups as unexposed due to missing pharmacy claims, only employer groups with at least 100 members in each year of the measurement period were included.

Members of selected employer groups eligible to be vaccinated with HZV or PV were identified. To be considered eligible, patients had to have continuous health plan eligibility during the baseline period (2012) and at least 1 day of health plan eligibility between January 1, 2013, and December 31, 2014. Patients were considered HZV-eligible if they were 50 years or older

 on January 1, 2013, and had no claims for HZV during the baseline period. Patients were considered PV-eligible if they were 19 years or older on January 1, 2013, and had no claims for PV during the baseline period. Additionally, per Advisory Committee on Immunization Practices (ACIP) recommendations and because the study population included patients 19 years or older, PV-eligible patients were required to have at least 1 claim with a diagnosis or procedure code for 1 of the conditions warranting PV during the baseline period (list in 

Patients with no claims for HZV in 2012 and who met the patient selection criteria during the study period were considered to be HZV-eligible. ACIP recommends 2 doses of PPV23 vaccine for all adults 65 years or older, with the second dose administered at least 5 years after the first dose. The PCV13 vaccine is indicated for all adults 50 years or older; however, ACIP also recommends use of this vaccine for adults (19 years or older) with immunocompromising conditions, followed by a dose of the PPV23 vaccine at least 8 weeks later.

 Patients were determined to be PV-eligible until they had a claim for both types of PV or the end of follow-up, whichever was earlier. Once patients reached the vaccination end point (ie, receipt of 1 dose of HZV or receipt of both PCV13 and PPV23), they were no longer considered vaccine-eligible for the remainder of the study. For example, if a patient received PCV13 and PPV23 in 2013, he or she would not be included in the 2014 vaccination rate calculation. Patients who did not reach the vaccination end point remained vaccine-eligible until the end of the continuous health plan eligibility or the end of the study period, whichever occurred earlier.

An employer group was assigned to the “exposed” study cohort if 1 or more members had at least 1 paid pharmacy claim for HZV, PV, or influenza vaccine between January 1, 2013, and December 31, 2014. An employer group was included in the “unexposed” study cohort if no member had any paid pharmacy claims for HZV, PV, or influenza vaccine between January 1, 2013, and December 31, 2014, and if at least 1 member had a paid medical claim for 1 of the other vaccines in that same period. Employer groups that had no pharmacy or medical claims for HZV, PV, or influenza between January 1, 2013, and December 31, 2014, were excluded because vaccine coverage status could not be determined. HZV- and PV-eligible and -vaccinated patients fell under the exposed and unexposed employer group category as per the employer group under which they were enrolled. 

Two sets of outcomes were assessed in parallel analyses for HZV and PV. First, the vaccination rates for exposed and unexposed cohorts were compared during 4 measurement periods to capture the vaccination rate across all meaningful combinations of follow-up time and continuous member eligibility criteria. Analysis of the subgroups of patients with 1 year or more of continuous eligibility allowed for uninterrupted follow-up at the cost of lower generalizability of results, whereas analysis of patients with at least 1 day of eligibility allowed for the evaluation of all patients qualifying for the study, but with uneven continuous follow-up. Comparisons within 2 annual cohorts for 2013 and 2014 controlled for year-specific factors impacting the outcome. Vaccination rates were measured among patients with at least 1 day of eligibility between January 1, 2013, and December 31, 2014 (Period A); and among patients continuously eligible between January 1, 2013, and December 31, 2013 (Period B); continuously eligible between January 1, 2014, and December 31, 2014 (Period C); and continuously eligible throughout the entire study period, between January 1, 2013, and December 31, 2014 (Period D).

The vaccination rate was computed as the number of vaccinated patients per 1000 vaccine-eligible person-years within the measurement period. Unvaccinated patients contributed person-years equal to their follow-up time within each measurement period. Vaccinated patients contributed person-years until the date on which they reached the vaccination end point. Person-years contributed by the vaccinated and unvaccinated patients were included in the vaccine-eligible person-years used in the calculation of vaccination rate.

Descriptive statistics were presented as means (SDs) and relative frequencies for continuous and categorical data, respectively, for baseline patient characteristics. Baseline characteristics were compared between exposed and unexposed cohorts using 

 tests for categorical variables. Differences in vaccination rates between exposed and unexposed cohorts were evaluated using the Pearson’s χ

A total of 7404 commercially insured employer groups with 2.83 million members had at least 100 enrollees each in 2013 or 2014. Patients belonging to 44 employer groups were excluded because of a lack of claims for HZV, PV, or influenza vaccine during 2013. The median number of members enrolled per employer group in the exposed cohort was 192 in 2013 and 194 in 2014; in the unexposed cohort, the median number of members was 196 in 2013 and 177 in 2014. 

After applying all inclusion and exclusion criteria, 457,631 HZV-eligible patients and 442,972 PV-eligible patients had at least 1 day of health plan eligibility in 2013 or 2014 (period A). Of 457,631 HZV-eligible patients, 34,623 (7.6%) had a claim for HZV; of 442,792 PV-eligible patients, 18,406 (4.2%) had a claim for PV.

The populations for the 3 additional measurement periods were derived from this total study population. Period B contained 6742 employer groups with 2.20 million members. Of the 457,550 HZV-eligible members, 17,562 (3.8%) had a claim for HZV; 442,442 members were PV-eligible, of whom 8644 (2.0%) were vaccinated. Period C consisted of 6863 employer groups with 2.38 million members. Of the 405,038 HZV-eligible members, 16,018 (4.0%) were vaccinated; 389,460 were PV-eligible, of whom 9184 (2.5%) were vaccinated. Period D consisted of 6250 employer groups with 1.90 million members. Of the 405,038 HZV-eligible members, 31,320 (7.7%) were vaccinated; 389,460 were PV-eligible, of whom 16,647 (4.3%) were vaccinated.

Among the 34,623 HZ-vaccinated patients with at least 1 day of health plan eligibility during the study period (period A), 32,903 (95.0%) were in the exposed cohort and 1720 (5.0%) were in the unexposed cohort (

). The mean age was slightly older in the exposed than the unexposed cohort (61.7 vs 60.6 years, respectively;

 <.001), although 25.6% in the exposed cohort were aged between 50 and 59 years. The exposed cohort had a slightly higher proportion of women than the unexposed cohort (54.6% vs 51.2%, respectively; 

Among the 18,406 PV-vaccinated patients, 16,612 (94.6%) were in the exposed cohort and 1794 (10.2%) were in the unexposed cohort, with similar mean age (57.7 vs 57.3 years, respectively; 

 = .20) and proportion of women (48.2% vs 48.4%, respectively; 

In period A, 32,506 in the exposed and 1299 in the unexposed cohort received HZV (

). In the exposed cohort, 395,842 HZV-eligible members contributed to 767,854 person-years; in the unexposed cohort, 43,141 HZV-eligible members contributed to 84,305 person-years. The vaccination rate was significantly higher among patients in the exposed group (0.042 vaccinations per eligible person-year, or 42 vaccinations per 1000 eligible person-years) compared with the unexposed group (0.015 vaccinations per eligible person-year, or 15 vaccinations per 1000 eligible person-years; 

Similar patterns were observed in the remaining 3 measurement periods (Table 2). In all measurement periods, vaccination rates were higher for patients in the exposed than unexposed cohorts (

In period A, 16,409 in the exposed and 1386 in the unexposed cohort received PV (

). In the exposed cohort, 382,767 PV-eligible members contributed to 742,476 person-years; in the unexposed cohort, 41,332 PV-eligible members contributed to 80,481 person-years. The vaccination rate was significantly higher among patients in the exposed (0.022 vaccinations per eligible person-year, or 22 vaccinations per 1000 eligible person-years) compared with the unexposed cohort (0.017 vaccinations per eligible person-year, or 17 vaccinations per 1000 eligible person-years; 

Periods B and D followed a similar pattern, with vaccination rates higher among patients in the exposed compared with the unexposed cohorts. Vaccination rates in the exposed and unexposed cohorts were not statistically significantly different in period C (Table 3 and Figure 2).

The results of this real-world analysis demonstrated that vaccination rates for HZV and PV were significantly higher among those whose commercial insurance plans covered vaccinations under both the medical and pharmacy benefit, compared with members whose insurance covered vaccines under the medical benefit only. With the exception of PV uptake in 2014, these results were consistent across 2013 and 2014 and for patients who had continuous as well as noncontinuous health plan enrollment.

While the exposed groups for both HZV and PV had higher vaccination rates than the unexposed groups, the differential was greater in the HZV group. A potential explanation is the requirement that HZV must be stored between —50°C and –15°C to maintain potency, requiring the use of a freezer. Unlike pharmacies, most physicians lack access to freezers and are therefore unable to store and administer HZV. Consequently, patients are likely to be recommended to receive HZV from a pharmacy instead.

 In contrast, PV can be stored at standard refrigerator temperatures; refrigerators, compared with freezers, are more likely to be found in physician offices. Therefore, the differences in vaccination rates for PV between exposed and unexposed cohorts were not as pronounced.

This study fills a gap in the literature by using a large, diverse population in a real-world setting. Although the patients included had a variety of health plan types, all had confirmed coverage for vaccines under medical and/or pharmacy benefits or under medical benefits alone. There were no between-group differences in co-pays for vaccines, as all study patients were commercially insured and did not have out-of-pocket co-pays for HZV and PV under the Affordable Care Act’s preventive care benefits. Thus, the difference in distribution of health plan benefits was unlikely to influence the observed different vaccination rates between the exposed and unexposed groups due to economic factors. All patients had equal follow-up periods and included those with continuous as well as intermittent health plan enrollment.

However, this study was subject to several limitations. The vaccination rates presented in this study are limited to a 3-year follow-up based on limited retrospective review of data. The proportion of vaccine-eligible patients was not adjusted for vaccinations given prior to January 1, 2012, potentially overestimating the number of vaccine-eligible patients in the exposed and unexposed cohorts. Lifetime follow-up of patients, although ideal, is challenging for patients who are likely to change their insurer with changes in employment or retirement. A single data source, such as a claims database or electronic health record, may be censored once a patient changes their physician, place of healthcare service, or insurer. Similarly, self-reported receipt of vaccination over longer time frames is also prone to limited or incorrect recall of the vaccine administered. A multivariable analysis was not conducted to control for other factors that may have affected vaccination rates. Coverageof HZV and PV under the pharmacy benefit was determined by the presence of pharmacy claims for these 2 vaccines, which may have resulted in false negatives due to an absence of observed pharmacy claims despite the employer group having provided coverage for the vaccines in the pharmacy benefit. This was mitigated to some extent by selecting groups with at least 100 members for each study year, thus diminishing the probability of false-negative assignment of unexposed status. Furthermore, the study also used the presence of claims for influenza vaccinations, which are highly prevalent in most commercial populations, as a proxy for pharmacy benefit—based coverage of PV and HZV to minimize chances of false negatives. It is possible that patients may have been vaccinated prior to the study period. Because vaccination prior to the study period was not captured and may have been substantially different for HZV and PV, vaccination rates between the 2 vaccines could not be compared.

Articles

By covering vaccinations under both the medical and pharmacy benefit, rather than the medical benefit alone, health insurers can help improve adult vaccination rates.

Impact of Medical and/or Pharmacy Reimbursement on Adult Vaccination Rates

 To examine the association of mail order versus retail pharmacy dispensing channels with medication adherence for patients on diabetes, hypertension, or high blood cholesterol  medications, controlling for prior adherence behavior (PAB) and days of supply.

 Retrospective analysis using de-identified pharmacy claims data from a large national pharmacy benefits manager between April 2009 and December 2011.

Continuously eligible patients with an antidiabetic, antihypertensive, or antihyperlipidemic prescription claim between October and December 2009 were identified and followed over a 2-year period. Multivariate logistic regression was used to evaluate the impact of dispensing channel on medication adherence, controlling for differences in demographics, disease burden, and drug use pattern. Patients with a medication possession ratio of 80% or greater were considered adherent. The analysis controlled for PAB by using patients’ adherence status in 2010.

 Overall, patients using the mail order channel had higher adherence rates than their retail counterparts across all 3 therapeutic classes. In 2011, the likelihood of a mail order patient being adherent was approximately 1.15 times higher than that of a retail patient for antidiabetics, 1.11 times higher for antihypertensives, and 1.19 times higher for antihyperlipidemics. PAB was the strongest contributor to the odds of a patient being adherent across all 3 therapy classes: odds ratios ranged from 5.87 to 9.49.

After adjusting for PAB, differential days of supply, and differences in demographics and disease burden, patients who use mail order have a greater likelihood of being adherent than patients who use a retail pharmacy.

The dispensing channel is an important contributor to improving maintenance medication adherence among patients. Given that patients’ prior adherence behavior might confound the relationship between channel and adherence, it is important to control for this effect in any channel-adherence analysis.

		Our study demonstrated that adherence is better with mail order than with retail pharmacies and is not just an artifact of increased days of supply.

		Prior adherence behavior is an important confounder in channel-adherence studies, and our study provides a reasonable proxy measure based on pharmacy claims data to lessen the impact of this confounder.

Medication adherence, defined as taking medications as prescribed, is a key component in controlling disease progression and managing chronic illnesses.

The clinical benefits of medication adherence have been well established in the scientific literature. Previous studies have indicated that medication adherence is associated with reducing disease morbidity,

 reducing healthcare resource utilization,

In addition to worse health outcomes, medication nonadherence is linked to increased healthcare costs. Nonadherence across just  chronic therapy classes (antidiabetics, antihypertensives, and antihyperlipidemics) resulted in an estimated $105.8 billion in direct costs in the United States during 2010 alone.

 Nevertheless, this cost burden can be reduced. Previous studies have found that adherence rates of 80% or greater were associated with significant decreases in total medical costs for diabetes, hypertension, and high blood cholesterol.

Studies have indicated that obtaining medication through the mail is one option for improved medication adherence.

 Compared with retail pharmacies, mail order has been touted as more cost-effective

 In contrast, retail pharmacies are perceived to add value in terms of pharmacist face-to-face interaction.

Proponents of mail order contend that medication  adherence is greater among patients who secure medications via mail order, while proponents of retail attribute any improved adherence to the increased days of supply per prescription in mail order.

Many patients who intend to take their medications as prescribed fail to get medications refilled due to various factors such as inability to visit a pharmacy, their schedule, forgetfulness, or procrastination. Mail order provides a convenient and effective alternative for continued access to medications. Inadequate access

are 2 factors identified as impediments to adherence.

 The impact of access and cost is reduced for many patients by the use of mail order, because  prescriptions are delivered to one’s home and the total patient out-of-pocket (OPP) costs are frequently less. Hence, we hypothesized that use of the mail order channel is associatedwith higher adherence rates than use of the retail channel.

A common limitation in adherence studies is the failure to control for underlying factors that affect adherence and selection of delivery channel. For example, it is quite possible that health-conscious individuals are more likely to have other healthy behaviors such as exercise, good diet, and preventive screenings. Hence, they may be more likely to engage proactively in activities that improve their adherence—sometimes referred to as the “healthy adherer” effect.

 Mail order generally provides more days of supply, regular refill reminders, and convenient reordering for members, mitigating the potential to procrastinate on medication refills, which can adversely affect adherence. Healthconscious individuals may choose the mail order channel to ensure continuity in their medication regimens. Thus, better medication adherence with mail order may reflect healthier patients’ predisposition to self-select the mail order option. To accurately attribute the impact of dispensing channel on adherence, it is important to control for bias from a patient’s predisposition to be adherent.

To our knowledge, previously published channel-adherence studies have not controlled for this potential confounder.

 A part of this effect, prior adherence behavior (PAB), can be controlled for by using a proxy measure—prior adherence, calculated based on pharmacy claims data. Also, most channel-adherence studies either have not fully controlled for differences in the days of supply between the 2 channels or have not taken patients’ choice of channel into account. This study aims to address the aforementioned biases and limitations, and tease out the effect of dispensing channel on adherence to medications to treat diabetes, hypertension, and high blood cholesterol.

This study used prescription claims data from a nationally representative sample of commercially insured members whose pharmacy benefits were managed by a large pharmacy benefit management company. Inclusion was limited to patients who were continuously enrolled for pharmacy benefits from April 1, 2009, until December 31, 2011, who were between the ages of 18 and 64 years, and who had any prescription claim for antidiabetics, antihypertensives, or antihyperlipidemics during the index period, which was from October 1, 2009, to December 31, 2009. Patients whose pharmacy benefit design required the use of mail order exclusively for maintenance medications or did not allow access to mail order (mandatory retail) at any time during the entire study period were excluded from analysis. That is, only those patients who were free to choose either channel at any time during the study to fill their maintenance prescriptions were selected. Under provisions of the Health Insurance Portability and Accountability Act of 1996, all data specific to individual patients were removed to maintain the privacy of protected health information from internal analytical data sets. All prescription claims were adjusted to 30-day equivalents.

A retrospective claims analysis over a 3-year period divided into 4 distinct phases (

) was conducted. A 6-month look-back period from April to September 2009 was used to assess whether the patients were new or continuing users of the medications identified. Patients having a claim within  the same therapy class under study in the look-back period were categorized as continuing users and those without claims as new users. This indicator attempted to capture any differences in adherence that resulted from the longevity of treatment. The analysis period for this study was from January 1, 2011, to December 31, 2011. As previous adherence may be indicative of a health-conscious personality and a measure of  better health-seeking behavior,

a patient’s prior adherence was used as a proxy control for self-selection bias due to the PAB effect in the multivariate model. Prior adherence was based on the patient’s medication possession ratio (MPR) in the year 2010, termed as the baseline period.

The primary outcome measure was patient adherence to diabetes, hypertension, or high blood cholesterol medications, defined as an MPR of 80% or greater

in the analysis period. Patients’ MPR was calculated as the total days of supply divided by 365 days, capping it at 100%. At the drug group level, the combination of 8-digit Generic Product Identifier (GPI) codes and clinically appropriate drug groups was used to calculate the MPR, which then was averaged to the therapy class level for each patient (

). Drug groups were based on clinically accepted drug subclasses within each therapy class. Only the numbers of medication units actually meant to be taken during the study periods were included in calculations. That is, the parts of any claim that  were in possession before the key periods (2010 for baseline and 2011 for analysis) and any excess in possession after the ends of the periods were excluded from the adherence calculations.

Based on a literature review, independent variables to be included in the model were identified. In addition to dispensing channel, other independent variables included prior adherence, age, sex, OOP costs for 30-day adjusted prescriptions, disease burden, severity of illness, location (urbanicity) of the patient, and average days of supply per claim. Channel was assigned to individuals based on where they obtained at least two-thirds (66.7%) of their 30-day adjusted prescriptions. Those who did not receive at least 66.7% of their 30-day adjusted prescriptions from either mail order or retail were assigned to a mixed channel group. Prior adherence was included in the model to control for the PAB effect, as past health behavior has been known to be a good marker for predicting future health behavior.

 A similar method was used in a 2011 study examining the association between statin use and outcomes that used prior adherence to control for the healthy-adherer effect.

 The MPR for 2010 was calculated for each patient to establish prior adherence, and patients with an MPR of 80% or greater were classified as adherent.

Patient demographics have been known to be significant confounders in assessing the relationship between dispensing channel and medication adherence.

 Age as of December 31, 2009, was used in the analysis. The OOP costs for 30-day adjusted prescriptions were calculated by dividing total OOP pharmacy costs (for each therapeutic class) for the patient in 2011 by that patient’s total number of 30-day adjusted prescriptions. In addition, proxy covariates controlled for patient disease burden and severity of illness. A patient’s overall disease burden was defined as the number of unique 2-digit GPIs, which indicate drug therapy classes used by the patient. The number of unique drug groups for which the patient had a prescription claim in 2011 defined severity of illness for diabetes and hypertension. For high blood cholesterol, only adherence to statins was analyzed and hence involved only 1 drug group. The location variable (urbanicity) was based on the core-based statistical area used by the US Census Bureau to ascertain the urban core of metropolitan and micropolitan statistical areas.

 Average days of supply per claim were used to control for the differences in days of supply of prescriptions between retail and mail order channels. The adherence rate was defined as the percentage of patients in each cohort (mail order/retail/mixed) who had an MPR of 80% or greater over the study period.

From a random sample of 4 million members, 109,794 diabetes patients, 467,054 hypertension patients, and 296,594 high blood cholesterol patients were identified between October and December 2009. 

) presents the sample selection methodology for the study, which resulted in final analytical samples of data for 37,639 diabetes, 152,819 hypertension, and 103,333 high blood cholesterol patients.

Descriptive statistics were estimated and bivariate differences between groups were tested using analysis of variance for all continuous variables and x

 tests for categorical variables. Multivariate logistic regression analyses were performed to estimate the association of aforementioned covariates with the odds of being adherent. In order to address the suggestion that better adherence with mail order is an artifact of more days of supply,

 average days of supply per claim was used as a proxy measure.

Additionally, an analysis on a subsample of patients filling exclusively 90-day prescriptions evaluated the impact of channel on adherence. Inclusion was limited to patients who filled all their prescriptions through 1 channel only (either retail or mail order). The final analytical subanalysis sample consisted of data for 7253 diabetes, 35,797 hypertension, and 32,391 high blood cholesterol patients. All analyses were conducted using SAS version 9.3 (SAS Institute Inc, Cary, North Carolina).

Generally, patients using mail order tended to be older and included a lower proportion of females than retail or mixed channels. Mail order patients had lower OOP costs per 30-day adjusted prescriptions, more average days of supply per claim, lower average disease burden, and marginally higher mean severity of illness (for diabetes and hypertension) than retailpatients. However, patients in the mixed group were more severely ill compared with mail order or retail patients. Across all 3 classes, prior adherence was significantly higher in mail order than in retail or mixed channels, reflecting the importance of using a proxy measure to control for PAB in the model in order to obtain less biased estimates of the effect of dispensing channel on adherence (

On average, mail order had 18.2% more adherent patients than retail and 21.6% more adherent patients than mixed channels across the 3 therapy classes. Unadjusted adherence rates for those using mail order were consistently higher than those for patients using retail, with percentage point differences ranging from 16.9% for high blood cholesterol medications to 20.3% for antidiabetic agents (

Subanalysis comparing 90-day retail patients with 90-day mail order patients also indicated that adherence rates were significantly higher in mail order compared with retail for users of hypertension (80.9% vs 76.3%; 

 <.001) and high blood cholesterol medication (76.9% vs 73.9%; 

 <.001). There was no significant difference in adherence rates for diabetes medication users among mail order and retail channel users (69.0% vs 67.3%; 

 indicate the significance of controlling for the PAB effect. Model 1 presents the odds of a patient being adherent without controlling for prior adherence behavior. Model 2 presented the odds of a patient being adherent controlling for the PAB effect. Prior adherence behavior had a significant impact on the results, as observed from the corresponding odds ratio (OR). It was the strongest contributor to the odds of a patient being adherent across all 3 therapy classes. ORs ranged from 5.87 to 9.49.

After controlling for relevant population differences (age, sex, and patient OOP cost per 30-day adjusted prescription) and key covariates (PAB, average days of supply per claim, disease burden, severity of illness, and urbanicity), the differences follow the same pattern as shown in model 1 (Table 2, model 2). In 2011, the likelihood of a mail order patient being adherent was approximately 1.15 times higher than that of a retail patient for antidiabetics, 1.11 times higher for antihypertensives, and 1.19 times higher for antihyperlipidemics. The odds of being adherent for a patient using mixed channels were approximately 20% to 30% lower than the odds for a retail patient for antidiabetics, antihypertensives, and antihyperlipidemics.

On average, mail order had 3.2% more adherent patients than retail and 10.2% more adherent patients than mixed channels across the 3 therapy classes. Adjusted adherence rates for those using mail order were consistently higher than those for patients using retail, with percentage point differences ranging from 2.3 for high blood pressure medications to 3.8 for antihyperlipidemics. The adjusted adherence rate for antidiabetics was 3.5% higher for patients using the mail order channel compared with patients using the retail channel.

Additional sensitivity analysis examining patients filling only 90-day prescriptions concluded that the adjusted odds of being adherent were significantly higher in mail order compared with retail for hypertension patients (OR = 1.19, 95% CI, 1.12-1.26) and high blood cholesterol patients (OR = 1.10, 95% CI, 1.03-1.18), indicating that mail order patients using antihypertensives and antihyperlipidemics were almost 19% and 10% more likely, respectively, to be adherent than their respective retail counterparts, even after equalizing the days of supply differential. There was no significant difference in the adjusted odds of being adherent between dispensing channels for diabetes patients (OR = 1.02, 95% CI, 0.90-1.16).

Mail order patients were significantly more adherent than their retail counterparts after controlling for demographics, drug use patterns, differences in days of supply, and the PAB effect. Although sensitivity analysis revealed no statistically significant difference for patients on diabetes medications, the findings from the main model were consistent across the 3 studied therapy classes. For hypertension and high blood cholesterol, patients classified as using a mixed channel had significantly lower adherence rates compared with patients who received 66.7% or more of their prescriptions from either retail or mail order. Controlling for the PAB effect, adjusting for the difference in days of supply in all models, and including only those patients who could exercise their choice of channel, the results offer strong evidence that mail order leads to greater odds of being adherent. The multivariate adjusted coefficients on age, sex, and OOP costs are consistent with previous research.

As this study used prior adherence to identify and control for the PAB effect, estimates of adherence behavior with respect to dispensing channel are less likely to be biased than those in any of the previous channel adherence studies.

This study makes an important methodologic contribution in the area by controlling for an important confounder—the PAB effect&mdash;which no previously published channel adherence studies took into account. Therefore, some results might have misattributed the impact of channel on adherence. Although 1 study on statins did address adherence and used prior adherence to identify healthy adherers in the context of outcomes, the study did not examine dispensing channel.

 To our knowledge, this study is the first to  address the concern of researchers who stressed the need to find a measure that controls for the confounding of patients’  predisposition to be adherent and to caution researchers to interpret the results of previous studies in light of this important limitation.

The results of this study should be interpreted in the context of its limitations. First, the study analyzed pharmacy administrative claims data, using medication possession as a proxy for medication-taking behavior. It assumed that a pill in hand is a pill taken, which is not always the case. However, the use of medication possession as a proxy for medication use has been well documented in previous studies.

Further, claims data cannot help distinguish between nonadherence and prescriber-recommended discontinuation. Second, because the study sample was limited to commercially insured patients aged 18 to 64 years, the results of the analyses may not be generalizable to other populations. Third, our ability to control for the confounding effects of covariates in the relationship between dispensing channel and adherence was limited by the reliability and validity of these proxy measures. We had access only to pharmaceutical claims data, and lack of medical information is a limitation of this study. Further studies should

look into medical covariates to strengthen the proxy variables. Lastly, we also were limited by our study design, because we included patients on medication for at least 2 years. Thus, patients who did not fill at least 1 prescription in each of the distinct time periods of the study were excluded from the analysis.

We found that patients receiving their medications via mail order had greater adherence than those receiving the medications via retail, even after accounting for differences in days of supply. Until now, to our best knowledge, channel adherence evaluations neither addressed the effect of prior adherence behaviors nor controlled for the difference in days of supply between channels. Thus, this study provides  empirically sound evidence that mail order is an important alternative to retail pharmacies for helping patients reach optimal adherence. By accounting for the biases resulting from the effect of prior adherence behavior and differential days of supply, this study demonstrates that the mail order channel is associated with improved adherence rates that are not simply a by-product of self-selection or increased days of supply.

Findings indicate that patients using mail order pharmacies had significantly better adherence to antidiabetics, antihypertensives, and antihyperlipidemics than patients who used the retail dispensing channel.

Jay Visaria, PhD, MPH

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