The Impact of 90-Day Prescriptions on Adherence at Workplace Pharmacies Compared to Traditional Mail Order

Abstract

This study evaluated adherence to medications used to treat chronic conditions for patients with 90-day prescriptions, comparing patients with access to workplace pharmacy services versus patients using mail order services. De-identified pharmacy claims data were used to compute medication possession ratio and gaps in therapy. Results were compared for patients who filled 90-day prescriptions at workplace pharmacies versus patients who filled 90-day prescriptions using mail order pharmacy services in a 1-year period. Statistical tests to assess between group differences were performed controlling for differences because of age, sex, number of select chronic conditions, number of unique medication therapeutic classes, and patient out-of-pocket cost per therapy day. Statistically significant differences were found between patients who filled their maintenance medications at the worksite compared to those who used mail-order pharmacy services. Patients filling prescriptions at a workplace pharmacy were 22% less likely to have a gap in therapy of over 30 days compared to similar patients using mail order services. Workplace pharmacy utilizers also had overall adherence rates 3.68% higher than patients who utilized mail order pharmacy services. Our analysis suggests that it may not be just the quantity of medication dispensed that impacts patients' adherence to their prescription medication, but a variety of other factors including pharmacist–patient interaction. Having a pharmacist on-site and available to patients with chronic considerations could provide added value. These results can aid employers and other stakeholders to decide which prescription benefits to offer their employees and members. (Population Health Management 2011;14:285–291)

Introduction

P atient adherence to prescribed therapy is important for achieving clinical goals, particularly for patients with chronic disease.¹ Nonadherence to medication increases the risk of disease complications and also can increase preventable health care costs and utilization.^2,3 Although there is strong evidence that poor adherence for patients with certain chronic conditions, such as hypertension,⁴ coronary artery disease,⁵ and diabetes,⁶ can increase adverse clinical outcomes and overall mortality,⁷ nonadherence remains an important barrier to treatment success and a leading challenge to health care professionals.⁸ It is estimated that 25%–50% of patients fail to receive the full benefit of medications prescribed because of lack of adherence⁹ and that half of chronically ill patients prescribed drugs stop taking their medication within 1 year.¹⁰ Sokol and colleagues found that higher rates of medication adherence for chronic conditions such as diabetes and hypertension were associated with net decreased medical costs, even though prescription costs increase with improved adherence.¹¹ In fact, the burden of medication nonadherence in the United States is estimated to be $100 billion in hospitalizations alone.¹² A report by the World Health Organization concluded that, worldwide, more health benefits would result from improving adherence to existing treatments than by developing new medical treatments, indicating the magnitude of nonadherence.¹³

Patient adherence to medications is a complex phenomenon involving numerous factors such as patient understanding of the condition being treated,^14,15 dosing frequency, prescription duration, patient out-of-pocket costs, age, sex, health status, and comorbidities.¹⁶ Patient adherence has a tendency to decline over time,^17,18 particularly for asymptomatic conditions such as hyperlipidemia and hypertension. Given the increase in the incidence and prevalence of chronic diseases in the United States¹⁹ and the aging of the population,²⁰ issues surrounding medication adherence are likely to increase.

Because employers are the major source of private health insurance in the United States,²¹ maximizing medication adherence rates represents an opportunity to lower health care costs as well as to improve the overall health of employees, retirees, and family members who are eligible to receive benefits.²² Employers struggle as the cost of health benefits increases faster than the rate of inflation, especially in light of the highly competitive global market.²³ In response to this, business leaders are investing in health and wellness offerings. One such approach is providing pharmacy services integrated with primary care at the workplace and including a benefit that allows for 90-day fills of maintenance medications at the workplace pharmacy. In comparison to traditional 30-day medication refills, 90-day fills reduce the number of times a person has to remember to refill their medication each year and is thought to make adherence easier because medication is on hand for longer periods of time.²⁴

Ninety-day fills are not a workplace-specific phenomenon. They have been offered by pharmacy benefit management (PBM) providers through mail order for many years²⁵ and are relatively well accepted, at least as inferred by the 13% of Americans prescribed drugs who have used mail order at least once.²⁶ Mail-order pharmacy providers have played an important role in increasing adherence through programs such as automatic refill, which automatically sends a new 90-day supply of medications to patients who opt for this and allow their bank or credit card to be charged automatically.²⁷ Nonetheless, the benefits of mail-order pharmacy remain inconclusive and without incentives or mandates, patients typically choose retail pharmacy over mail order.²⁸ One way to reduce costs, increase adherence, and still allow for patient choice of distribution channel is for pharmacy benefit plans to allow 90-day prescription refills at worksite and retail pharmacies as well as via mail order.²⁹

A recently published study found that the use of workplace pharmacy integrated with primary care had a positive impact on overall medication adherence relative to medications dispensed at retail pharmacy locations.³⁰ The current study extends this research to examine medication adherence for patients with 90-day prescriptions, comparing patients with access to workplace pharmacy services versus patients using traditional PBM mail order services.

Published research is scant at best regarding the effect of 90-day prescriptions on adherence and gaps in therapy^31,32 and, to our knowledge, no studies have examined the impact on patient adherence of mail order versus interactions where pharmacists are on-site for 90-day fills. We hypothesize that patients who obtain their maintenance medications for chronic conditions using 90-day fills at the workplace pharmacy have higher adherence rates and that fewer patients will have significant gaps in therapy than similar patients who obtain their maintenance medications using traditional 90-day mail-order fills. The rationale behind our conjecture derives its strength from the Health Belief Model.³³ This model theorizes that health-related action depends on a patient being motivated to make health issues relevant. We believe that an environment that facilitates direct face-to-face interaction with a trusted pharmacist has an influence on patient motivation,^34,35 contributing to increased medication adherence. We also hypothesize that the convenience of a workplace pharmacy and the relationship with the trusted pharmacist will reduce the percentage of patients who have a gap in therapy of greater than 30 days.

Methods

Patient population

The population with health benefit coverage from 8 different locations of a large, self-insured employer, including both active employee and retiree populations together with their eligible dependents, was selected for potential inclusion in this study. De-identified demographic and pharmacy claims data were obtained for all dates of service during the time period of January 1, 2006 through December 31, 2007. Four of the 8 locations had primary care and pharmacy services available at the worksite. All locations had the same health plan benefit design, and the 4 workplace health center locations have been continuously operated by the same workplace health vendor for over 15 years. The workplace pharmacies were available exclusively to employees, retirees, and their family members. These pharmacies were located directly at the worksite or on employer property adjacent to work locations in order to be accessed by dependants. Also, because these pharmacies are colocated with the company's health center, the pharmacist and physician collaborate to ensure appropriate treatment by performing medication therapy management and drug use review.

Calendar year 2006 was selected as the baseline year from which the populations were separated into their respective analysis groups, and calendar year 2007 was the study year from which medication adherence and therapy gaps were determined using the methods to be described. Although the study focused on adherence rates for 2007, the last 2 quarters of 2006 were included to capture prescriptions filled in 2006 that would carry over for the number of days supplied into 2007. For example, if a prescription for a 90-day supply of a given drug was filled on December 1, 2006, the 60 days of supply remaining on January 1, 2007 were included in the study.

All patients of the 8 locations who were continuously eligible for pharmacy benefits between January 1, 2006 and December 31, 2007 and who had at least 1 pharmacy claim for a 90-day supply of prescription medication for at least 1 disease of interest (coronary artery disease [CAD], congestive heart failure [CHF], diabetes, hypertension, and hyperlipidemia) filled during calendar year 2007 were selected for inclusion (n = 18,252). Medication therapeutic classes, identified by associating the National Drug Code (NDC) for each pharmacy claim with the appropriate American Hospital Formulary Service (AHFS) number, were used to determine the presence of the diseases of interest. Medication adherence and gaps in therapy for the following therapeutic classes were evaluated: angiotensin II converting enzyme inhibitors, angiotensin II receptor antagonists, beta-blockers, biguanides, bile acid sequestrants, calcium channel blockers, cardiac glycosides, diuretics, fibric acid derivatives, HMG reductase inhibitors, sulfonylureas, and thiazolidinediones. All other patients were excluded.

Patients were then grouped based on the manner in which their 90-day prescriptions were filled. Patients who had access to a workplace pharmacy for medication fulfillment and who utilized it for at least 1 prescription fill for a 90-day supply were selected into the group, “90-Day Workplace Rx.” It should be noted that the patients in this group had the option of using community pharmacies for prescriptions of 30-days or less and mail order services for 90-day prescriptions in addition to the workplace pharmacy. Patients using both the workplace pharmacy and mail order accounted for 7.9% (n = 899) of the 90-Day Workplace Rx group (40.7% [n = 366] of these patients did not use mail order after filling at the workplace pharmacy). Patients without access to a workplace pharmacy were only able to fill 90-day prescriptions via mail order. Patients in this group with at least 1 fill for a 90-day prescription were included in the “90-Day Mail-Order” group.

For each therapeutic class within both groups, patients who had more than one 30-day fill during the study year (2007) following the initial 90-day fill of medications within the same therapeutic class were excluded (2.81% of workplace pharmacy occurrences and 3.80% of mail order occurrences), as this type of fluctuation in days of supply may be indicative of clinical intervention by the patient's health care provider and is beyond the scope of this study. Descriptive information on the study groups can be seen in Table 1.

Table 1.

Study Population Characteristics

	90-Day Workplace Rx (n = 11,339)	90-Day Mail Order (n = 6913)	P Value
Mean age (SD)	66.13 (12.52)	63.73 (10.11)	<0.0001
Male, %	54.98	56.92	0.0103
Mean number of select chronic conditions^*	1.64	1.63	0.5712
Mean number of therapeutic classes	9.56	9.23	<0.0001
Mean patient co-pay cost per therapy day	$.23	$.31	<0.0001
Mean employer paid Rx cost per therapy day	$.76	$1.02	<0.0001
Mean total Rx cost per therapy day	$1.00	$1.33	<0.0001
Patients new to therapy, %	17.19	15.73	<0.0001
One-time therapeutic class fill patients, %	13.64	12.30	<0.0001

Select chronic conditions are: asthma, chronic obstructive pulmonary disease, coronary artery disease, congestive heart failure, hypertension, diabetes, and hyperlipidemia.

Measuring adherence and gaps in therapy

We used 2 proxy measures: medication possession ratio (MPR) and gaps in therapy of greater than 30 days, to calculate medication adherence. MPR was computed as number of actual adherent days divided by the number of potential adherent days, where actual adherent days is the number of days that the patient had the medicine available from the date of service of the initial prescription for each therapeutic class through December 31, 2007 and potential adherent days is the number of days from the date of service for the first prescription for each therapeutic class through December 31, 2007.

Percent with a therapy gap was calculated as the number of patients who experienced a continuous gap between the date a refill was anticipated (ie, 90 days from the fill date) and the date of the next refill of 30 days or more at least once during the 12-month measurement period divided by the number of patients who filled at least 1 prescription for a drug in the therapeutic class. Therapy gaps present a considerable challenge in attempts to help patients persist on medications because once a patient has allowed a significant amount of time to elapse without taking his/her medication, he/she is at greater risk of discontinuing use of the medication altogether.³⁶

Two comments are worth noting. First, both MPR and therapy gaps were calculated for each patient-therapeutic class combination regardless of whether the patient was new to therapy or an established patient. Because employers and other stakeholders are necessarily more interested in population-level measures as compared to individual-level measures, as the patient's clinician might be, this study reflects the prescription filling behavior of a population of patients at all points in their drug treatment continuum. Second, MPR and gaps in therapy are medication-specific measures rather than patient-specific measures in this study. Conditions such as diabetes, heart disease, and hypertension can be treated using many combinations of medications as well as other medical and lifestyle interventions, all of which can change over time in accordance with the patient's disease progression and overall health.^37,38 Thus, patients taking different medications in different therapeutic classes may have different adherence measures for each therapeutic class.

Statistical analysis

We used the nonparametric estimates of χ² for the comparison of differences between the groups when the variables were categorical with non-normal distribution. For continuous variables, we used the Student t test for simple comparisons of differences between the groups. A linear regression model was used to calculate adjusted P values using age, sex, number of therapeutic classes, average co-pay per therapy day, patients new to therapy (patients who did not have a prescription fill for a particular therapeutic class in the preceding year), and number of the following chronic conditions: asthma, chronic obstructive pulmonary disease, CAD, CHF, hypertension, hyperlipidemia, and diabetes. For all statistical tests, a 2-tailed P value of <0.05 was considered statistically significant. All statistical analyses were performed with SAS statistical software, version 9.1.3 (SAS Institute Inc, Cary, NC).

Results

As shown in Table 1, the 90-Day Workplace Rx group consisted of 11,339 patients who were an average of 66 years of age and filled prescriptions for an average of 9.56 different therapeutic classes. These patients were predominantly male (54.98%) with a $0.23 average patient co-pay per therapy day. The 90-Day Mail-Order group comprised 6913 patients who were an average of 64 years of age and filled prescriptions for an average of 9.23 unique therapeutic classes. This group was primarily male (56.92%) with a $0.31 average patient co-pay per therapy day. Patients with a 1-time fill for a particular therapeutic class and patients who were new to therapy in at least 1 of the therapeutic classes accounted for 13.64% and 17.19%, respectively, of the workplace patients, compared to 12.30% and 15.73%, respectively, of the mail-order patients.

Patients who filled 90-day scripts at the workplace had a significantly higher MPR across all 12 therapeutic classes combined compared to those patients who filled 90-day scripts via mail order (81.14% vs. 78.26%, P < 0.0001). The same result was observed when looking at all therapeutic classes combined by condition: CAD, CHF, diabetes, hypertension, and hyperlipidemia. The 90-Day Workplace Rx patients also had a significantly higher MPR when examining therapeutic classes individually, except for bile acid sequestrants. Results are shown in Table 2.

Table 2.

Medication Possession Ratio: 90-Day Workplace Rx vs. 90-Day Mail Order

	MPR, %
Therapeutic Class	90-Day Workplace Rx (n = 11,390)	90-Day Mail Order (n = 6,913)	Net Difference (%)	Percent Difference	P	Adjusted P Value ^*
Angiotensin II converting enzyme inhibitors	82.85	79.92	2.93	3.67	<.0001	<.0001
Angiotensin II receptor antagonists	83.45	79.05	4.41	5.57	<.0001	<.0001
Beta-blockers	82.96	79.04	3.92	4.96	<.0001	<.0001
Biguanides	80.49	76.27	4.22	5.54	<.0001	<.0001
Bile acid sequestrants	68.85	72.59	−3.74	−5.15	0.3119	0.0471
Calcium channel blockers	83.58	80.57	3.01	3.73	0.0040	0.0111
Cardiac glycosides	82.08	80.40	1.68	2.09	0.3618	0.01
Diuretics	78.53	78.11	0.42	0.54	0.4884	0.0031
Fibric acid derivatives	81.63	76.69	4.94	6.44	<.0001	<.0001
HMG reductase inhibitors	79.98	77.45	2.53	3.27	<.0001	<.0001
Sulfonylureas	81.53	79.52	2.02	2.54	0.0291	<.0001
Thiazolidinediones	77.18	73.85	3.33	4.50	0.0027	0.0003
All 12 therapeutic classes	81.14	78.26	2.88	3.68	<.0001	<.0001
CAD therapeutic classes combined	85.31	81.85	3.46	4.23	<.0001	<.0001
CHF therapeutic classes combined	85.51	82.46	3.05	3.69	<.0001	<.0001
Diabetes therapeutic classes combined	85.37	81.88	3.48	4.26	<.0001	<.0001
Hyperlipidemia therapeutic classes combined	80.43	77.70	2.73	3.51	<.0001	<.0001
Hypertension therapeutic classes combined	85.74	82.73	3.00	3.63	<.0001	<.0001

CAD, coronary artery disease; CHF, congestive heart failure; HMG, hydroxymethyl glutaryl.

Adjusted for sex, age, number of select chronic conditions, number of therapeutic classes, number of patients new to therapy, and average co-pay per therapy day.

The percentage of patients who experienced a gap in therapy of greater than 30 days was significantly less for the 90-Day Workplace Rx group (Table 3). Across all 12 therapeutic classes combined, 45.02% of the patients in this group had gaps in therapy of greater than 30 days compared to 57.84% of the 90-day Mail-Order group (P < 0.0001). Results were consistent when combining therapeutic classes into specific conditions and when stratifying by individual therapeutic class, except for bile acid sequestrants.

Table 3.

Percent with Gap in Therapy of >30 Days: 90-Day Workplace Rx vs. 90-Day Mail Order

	Patients, %
Therapeutic Class	90-Day Workplace Rx (n = 11,390)	90-Day Mail Order (n = 6,913)	Net Difference (%)	Percent Difference	P	Adjusted P Value ^*
Angiotensin II converting enzyme inhibitors	40.89	55.01	−14.12	−25.66	<.0001	<.0001
Angiotensin II receptor antagonists	40.37	56.16	−15.79	−28.12	<.0001	<.0001
Beta-blockers	40.61	57.93	−17.31	−29.89	<.0001	<.0001
Biguanides	47.20	60.88	−13.67	−22.46	<.0001	<.0001
Bile acid sequestrants	69.03	67.86	1.17	1.72	0.8624	0.0316
Calcium channel blockers	37.80	52.43	−14.63	−27.91	<.0001	<.0001
Cardiac glycosides	40.67	53.70	−13.03	−24.26	0.0055	0.0065
Diuretics	50.21	58.60	−8.40	−14.33	<.0001	<.0001
Fibric acid derivatives	44.90	60.87	−15.97	−26.24	<.0001	<.0001
HMG reductase inhibitors	48.58	58.70	−10.13	−17.25	<.0001	<.0001
Sulfonylureas	45.97	56.33	−10.36	−18.40	<.0001	0.0002
Thiazolidinediones	50.20	64.36	−14.16	−22.00	<.0001	<.0001
All 12 therapeutic classes	45.02	57.84	−12.82	−22.17	<.0001	<.0001
CAD therapeutic classes combined	35.72	50.79	−15.06	−29.66	<.0001	<.0001
CHF therapeutic classes combined	35.36	49.15	−13.79	−28.05	<.0001	<.0001
Diabetes therapeutic classes combined	35.85	49.91	−14.06	−28.16	<.0001	<.0001
Hyperlipidemia therapeutic classes combined	47.63	58.37	−10.74	−18.40	<.0001	<.0001
Hypertension therapeutic classes combined	34.75	48.73	−13.98	−28.69	<.0001	<.0001

CAD, coronary artery disease; CHF, congestive heart failure; HMG, hydroxymethyl glutaryl.

Adjusted for sex, age, number of select chronic conditions, therapeutic class count, number of patients new to therapy, and average co-pay per therapy day.

Discussion

Our results indicate that overall, patients who received 90-day supplies of medication from a pharmacist who was available on-site at a workplace pharmacy experienced improved rates of adherence and reduced gaps in therapy compared to those patients who received a 90-day supply via mail order. The ability to fill a 90-day script at a workplace pharmacy offers several advantages over mail order, all of which could improve medication adherence and persistence.

The ability of a pharmacist to interact with patients in person could help foster relationships that build trust and understanding, providing pharmacists with opportunities to effectively counsel and educate their patients on the importance of medication adherence, and on their health. Face-to-face interactions between pharmacists and patients provide opportunity to counsel patients on proper medication usage, answer patients' questions about their medications, and provide information about the drugs themselves. Pharmacists have long been shown to be effective in helping to improve the health outcomes of their patients.^39,40,22 Patients who have an established relationship with their pharmacist may be encouraged to take a more proactive role in managing their health. Moreover, patients who utilize workplace and community pharmacies are able to seek and obtain counseling and guidance from a pharmacist on the spot, right when needed, which provides the opportunity to address any issues that may be hindering patients from achieving optimal medication adherence. In contrast, obtaining prescription medications via mail order, although perhaps a more cost-effective transaction, is not conducive to establishing a patient–pharmacist relationship. Therefore, crucial opportunities to counsel and educate patients may be lost.

Having medication filled through mail order requires advance planning. Patients must either request their refills days before the script runs out, in order to ensure that they always have a supply of the medication on hand, or set up an automatic refill for their medications, which some patients might be uncomfortable with and can result in waste if the patient's prescription changes. If the medication order is not placed within the right time frame, optimal medication adherence can be jeopardized. Allowing a 90-day script to be filled at a workplace pharmacy allows patients to receive their medications in real time. A pharmacist at a worksite also may reach out to a patient's physician, allowing for continuity of care.

In our study, 90-Day Workplace Rx patients were able to fill their prescriptions at a pharmacy located at or adjacent to their worksite. The provision for a 90-day supply of medication at a workplace pharmacy may provide additional benefits that could lead to increased adherence for that portion of the employees in the study population. Most employees spend a great deal of their time at work. Therefore, the convenience of being able to have prescriptions filled at the workplace may in and of itself increase adherence and impact productivity and absenteeism. This increased access could enable patients to have their medications on hand and minimize gaps in therapy. Workplace pharmacy patients had more than one option for 90-day prescription fulfillment. This flexibility also could affect medication adherence. Furthermore, our results indicate that patients who utilize workplace pharmacies for their prescription needs have lower average prescription costs per therapy day than those who use mail order. This savings benefited both the patient and the employer; workplace pharmacy patients were able to experience lower average co-pays and the employer benefited with a lower average employer share (Table 1). The ability of a workplace pharmacy to increase medication adherence also could lead to medical cost savings. A study by Balkrishnan and colleagues predicted patients with diabetes to have a decrease in direct medical costs of at least 8.6% for every 10% increase in medication adherence.⁴¹ Although the improvement in adherence was not as large as 10%, it could nonetheless result in some savings. Therefore, providing a workplace pharmacy in which employees can fill their prescription drug needs could provide savings to employers and employees in several different ways.

Patients in the 90-Day Workplace Rx group were able to achieve an overall MPR of 81.14% across the 12 therapeutic classes combined, whereas the 90-Day Mail-Order group had an overall MPR of 78.26%. The patients in the workplace group were also able to achieve an MPR of over 80% for 8 of the 12 therapeutic classes individually, compared to only 2 therapeutic classes for the mail-order group. The availability of obtaining 90-day supplies at the workplace not only significantly impacts overall measures of adherence compared to utilizing mail order but also helps achieve the 80% medication adherence level, which is considered an important factor in effectively managing chronic conditions such as diabetes, hypertension, and CHF.¹¹ Although the clinical significance of the observed increased medication adherence may be small, any effort to improve medication adherence is likely to improve patient outcomes.

Further studies are needed to assess the impact of a worksite pharmacy on productivity and absenteeism. In addition, studies that directly measure the impact on adherence of patients who have substantive face-to-face or telephonic interaction with pharmacists are needed, as are studies that assess the impact that specific pharmacy services have on adherence.

Limitations

Our study has several limitations. First, the measures used in our analyses of compliance are proxy measures for the actual rate at which patients took their medication. We are not able to measure the actual ingestion of medication by a patient, nor are we able to measure any medications that were supplied by the physician or for which the patients paid cash. Our estimates represent the upper bounds of actual adherence. The percent with therapy gap is inflated to 100% for patients with only 1 fill. Second, because our study utilizes claims data, no consideration is given for physician-ordered discontinuation of medication during the study period. This has the potential to negatively influence medication adherence measures. Furthermore, the observed differences in adherence may not be large enough to produce significant clinical changes and clinical outcomes from increased adherence can vary by disease state. The clinical implications of the differences in medication adherence were not evaluated but should be addressed by future research. Because this was a retrospective study, patients were not randomized to their respective groups. Therefore, the observed differences in adherence could be the result of population differences. In addition, despite controlling for factors that knowingly influence adherence, there may residual confounding or unknown factors that were not controlled for in this study. Finally, this study is based on 1 specific employer with a slightly older population, potentially limiting the ability to generalize to other employers and age groups.

Conclusion

This study demonstrated that patients who filled 90-day prescriptions at a workplace pharmacy had greater rates of adherence than patients who used mail-order services for their 90-day prescription fulfillment. Our analysis suggests that it may not be just the quantity of medication prescribed, but a variety of other factors that influence a patient's adherence to their prescription medication including convenience and pharmacist-patient interaction. This study can aid employers to decide which prescription benefits to offer their employees.

Footnotes

Author Disclosure Statement

Drs. Patwardhan and Khandelwal, Mr. Davis, and Ms. Murphy are employees of Walgreen Co., the funder of this study. Mr Manfred is an employee of Take Care Health Systems, which is a wholly owned subsidiary of Walgreen Co. Take Care Health Systems provides workplace pharmacy services as described in this article. Dr Sherman reports no relationship or financial interest with any entity that would pose a conflict of interest.

Funding Source: Self-funded by Walgreen Co.

References

DiMatteo

, Giordani

, Lepper

, Croghan

. Patient adherence and medical treatment outcomes: A meta-analysis. Med Care, 2002; 40:794–811.

Vermeire

, Hearnshaw

, Van Royen

, Denekens

. Patient adherence to treatment: Three decades of research. A comprehensive review. J Clin Pharm Ther., 2001; 26:331–342.

Dennehy

, Kishi

, Louie

. Drug-related illness in emergency department patients. Am J Health Syst Pharm, 1996; 53:1422–1426.

Munger

, Van Tassess

, LaFleur

. Medication nonadherence: An unrecognized cardiovascular risk factor. Med Gen Med, 2007; 9:58.

, Magid

, Shetterly

et al. Medication nonadherence is associated with a broad range of adverse outcomes in patients with coronary artery disease. Am Heart J, 2008; 155:772–779.

, Rumsfeld

, Masoudi

et al. Effect of medication nonadherence on hospitalizations and mortality among patients with diabetes mellitus. Arch Intern Med, 2006; 166:1836–1841.

Simpson

, Eurich

, Majumdar

et al. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ, 2006; 333:15–20.

Miller

, Hill

, Kottke

, Ockene

. The multilevel compliance challenge: Recommendations for a call to action. A statement for healthcare professionals. Circulation, 1997; 95:1085–1090.

Roter

, Hall

, Merisca

, Nordstrom

, Cretin

, Svarstad

. Effectiveness of interventions to improve patient compliance: A meta-analysis. Med Care, 1998; 36:1138–1161.

10.

Wahl

, Gregoire

, Teo

et al. Concordance, compliance and adherence in healthcare: Closing gaps and improving outcomes. Healthc Q, 2005; 8:65–70.

11.

Sokol

, McGuigan

, Verbrugge

, Epstein

. Impact of medication adherence on hospitalization risk and healthcare cost. Med Care, 2005; 43:521–530.

12.

Osterberg

, Blaschke

. Adherence to medication. N Engl J Med, 2005; 353:487–497.

13.

World Health Organization (WHO). Adherence to long-term therapies: evidence for action. http://whqlibdoc.who.int/publications/2003/9241545992.pdf. 2009 June 10.

14.

Keller

, Wright

, Pace

. Impact of health literacy on health outcomes in ambulatory care patients: A systematic review. Ann Pharmacother, 2008; 42:1272–1281.

15.

McCann

, Bovbjerg

, Brief

, Turner

. Relationship of self-efficacy to cholesterol lowering and dietary change in hyperlipidemia. Ann Behav Med, 1995; 17:221–226.

16.

National Council on Patient and Information. Education. Enhancing prescription medicine adherence: a national action plan. www.talkaboutrx.org/documents/enhancing_prescription_medicine_adherence.pdf. 2008 August 23.

17.

Lee

, Grace

, Taylor

. Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: A randomized controlled trial. JAMA, 2006; 296:2563–2571.

18.

Dunbar-Jacob

, Erlen

, Schlenk

, Ryan

, Sereika

, Doswell

. Adherence in chronic disease. Annu Rev Nurs Res, 2000; 18:48–90.

19.

, Green

. Projection of Chronic Illness Prevalence and Cost Inflation. Washington, DC: RAND Corporation, October 2000.

20.

U.S. Census Bureau. Annual projections of the resident population by age, sex, race, and Hispanic origin: lowest, middle, highest series and zero international migration series. 1999 to 2100http://www.census.gov/population/www/projections/natdet-D1A.html. Accessed June 10, 2009.

21.

Blumenthal

. Employer-sponsored insurance—Riding the health care tiger. N Engl J Med, 2006; 355:195–202.

22.

Fera

, Bluml

, Ellis

. Diabetes Ten City Challenge: Final economic and clinical results. J Am Pharm Assoc, 2009; 49:383–391.

23.

Mercer. Health benefit cost growth predicted to ease slightly in 2009 as employers shift cost. http://www.mercer.com/summary.htm?idContent=1319885. 2009 June 20.

24.

Coombs

, Cornish

, Hiller

, Smith

. Compliance and refill pattern behavior with HMG-CoA reductase inhibitors after acute myocardial infarction. Manag Care Interface, 2002; 15:54–60.

25.

Carroll

, Brusilovsky

, York

, Oscar

. Comparison of costs of community and mail service pharmacy. J Am Pharm Assoc, 2005; 45:336–343.

26.

Stagnitti

. Comparing population characteristics of persons purchasing prescribed drugs from mail order pharmacies with persons purchasing prescribed drugs from other outlets. 2005. http://www.meps.ahrq.gov/mepsweb/data_files/publications/st200/stat200.pdf. 2009 June 2.

27.

Brown

, Rickles

. Mail-order versus local pharmacies on adherence: Study methods make for unfair comparison. Am J Manage Care, 2010; 16:226–227.

28.

Clark

, Siracuse

, Garis

. A comparison of mail-service and retail community pharmacy claims in 5 prescription benefit plans. Res Social Adm Pharm, 2009; 5:133–142.

29.

Edlin

Mari

. Retail pharmacies fill 90-day prescriptions to compete with mail. http://managedhealthcareexecutive.modernmedicine.com/mhe/Pharmacy+Best+Practices/Retail-pharmacies-fill-90-day-prescriptions-to-com/ArticleStandard/Article/detail/314991. 2010 April 20.

30.

Sherman

, Frazee

, Fabius

, Broome

, Manfred

, Davis

. Impact of workplace health services on adherence to chronic medications. Am J Manag Care, 2009; 15:21–27.

31.

Valluri

, Seoane-Vazquez

, Rodriguez-Monguio

, Szeinbach

. Drug utilization and cost in a Medicaid population: A simulation study of community vs. mail order pharmacy. BMC Health Serv Res, 2007; 7:122.

32.

Steiner

, Robbins

, Roth

. The effect of prescription size on acquisition of maintenance medications. J Gen Intern Med, 1993; 8:306–310.

33.

Rosenstock

, Strecher

, Becker

. Social learning theory and the Health Belief Model. Health Educ Q, 1988; 15:175–183.

34.

Hibbard

, Mahoney

, Stock

, Tusler

. Do increases in patient activation result in improved self-management behaviors? Health Serv Res, 2007; 42:1443–1463.

35.

Bandura

. Self-efficacy mechanism in physiological activation and health-promoting behavior. Madden

, Matthysse

, Barchas

. Adaption, Learning, and Affect. New York: Raven Press, 1991; 226–269.

36.

Hansen

, Dusetzina

, Dominik

, Gaynes

. Prescription refill records as a screening tool to identify antidepressant non-adherence. Pharmacoepidemiol Drug Saf, 2010; 19:33–37.

37.

Chobanian

, Bakris

, Black

et al. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, National Heart, Lung, and Blood Institute, National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension, 2003; 42:1206–1252.

38.

Nathan

, Buse

, Davidson

et al. American Diabetes Association, European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 2009; 32:193–203.

39.

Bunting

, Cranor

. The Asheville Project: Long-term clinical, humanistic, and economic outcomes of a community-based medication therapy management program for asthma. J Am Pharm Assoc, 2006; 46:133–147.

40.

Bunting

, Smith

, Sutherland

. The Asheville Project: Clinical and economic outcomes of a community-based long-term medication therapy management program for hypertension and dyslipidemia. J Am Pharm Assoc, 2008; 48:23–31.

41.

Balkrishnan

, Rajagopalan

, Camacho

, Huston

, Murray

, Anderson

. Predictors of medication adherence and associated health care costs in an older population with type 2 diabetes mellitus: A longitudinal cohort study. Clin Ther, 2003; 25:2958–2971.