Medication Adherence for 90-Day Quantities of Medication Dispensed Through Retail and Mail Order Pharmacies
Nikhil Khandelwal, PhD, BPharm; Ian Duncan, FSA, FIA, FCIA, MAAA; Elan Rubinstein, PharmD, MPH; Tamim Ahmed, PhD, MBA; Cheryl Pegus, MD, MPH; Patricia Murphy, MPH; and Kenneth E. Kudrak, ASA, MS, MA
Patient adherence to medication therapy is an important aspect in the management of chronic diseases. Studies show that medication nonadherence is associated with increased hospitalizations and mortality for patients with chronic diseases, such as diabetes and coronary artery disease.1-3
Despite the adverse effects of poor medication adherence, it is estimated that on average, 50% of patients do not take their medication as prescribed.4
Medication nonadherence carries a significant financial burden as well, estimated to be $100 billion for hospitalizations alone,5
impacting patients, employers, and health plans. However, these excess costs can be prevented. A study by Sokol et al6
found that medication adherence rates of 80% and higher are associated with decreased total medical costs for diabetes, high cholesterol, and hypertension. Furthermore, Balkrishnan et al7
showed that for diabetes every 10% increase in medication adherence could help cut medical costs by 8.6%.
Many more Americans are using prescription drugs,8
a trend that is likely to continue as the US population ages9
and as the prevalence of chronic conditions increases.10
As a result, health plan sponsors have been seeking ways to improve adherence and impact overall healthcare costs.
Mail order pharmacy is one channel for dispensing 90-day supplies of maintenance medications that pharmacy benefit managers (PBMs) have been using to help control prescription costs and increase generic utilization.11,12
Mail order pharmacy provides patients with the convenience of having medication delivered to their homes, while incurring lower costs through a reduced copayment incentive.12
Some studies indicate use of mail order pharmacy may also contribute toward greater medication adherence.13,14
While patients using mail order pharmacy generally have access to a toll-free number for medication questions, they lose the ability to have a face-to-face interaction with a pharmacist,11
particularly when filling by mail order is mandatory rather than optional.
Retail pharmacies also offer fulfillment of 90-day supplies of medication.15
This was implemented in an effort not only to compete with mail order pharmacy, but also to offer patients increased options for 90-day prescription fulfillment.15
Retail pharmacies, as a channel for fulfillment of maintenance prescriptions, offer several advantages over mail order pharmacy. First, patients seem to prefer filling their prescriptions at retail pharmacies compared with mail order, as demonstrated by higher utilization rates for retail pharmacies, regardless of incentive to use mail order.16
Second, this allows patients who prefer to fill their prescriptions at retail pharmacies the added convenience of doing so for all of their 30-day and 90-day medication needs. Third, retail pharmacies offer patients the opportunity to have face-to-face consultations with a pharmacist to address any concerns they may have about their medications. Finally, pharmacists are provided with an opportunity to proactively counsel patients on the importance of taking their medicines as prescribed, which has been demonstrated to improve adherence rates.17
The objective of this study was to compare medication adherence of patients who fill 90-day quantities of maintenance medications through retail versus mail order channels. We limited our analysis to prescriptions of 90-day quantities, rather than 30-day quantity fills, because maintenance-drug patients using this quantity of refills are likely to be stabilized with respect to medication and dosing regimen.18
To our knowledge, this is the first study to compare medication adherence between the 2 delivery channels for 90-day prescriptions. We hypothesize that patients filling 90-day prescriptions at retail pharmacies will have adherence rates similar to those of patients employing mail order pharmacy.
This retrospective cross-sectional analysis used de-identified demographic and pharmacy claims data obtained from alarge PBM database covering the 2-year period from January 1, 2008, to August 31, 2010. All patients who were continuously eligible for at least 12 months during this time and had a pharmacy benefit plan design that allowed for prescription fulfillment of 90-day supplies at either a retail pharmacy or by mail order with equal copays were considered for inclusion. Equivalence of benefits was determined by analyzing the distribution of patient cost sharing by client year, distribution channel, and drug type (generic, preferred, non-preferred), excluding claims where the patient payment amount was equal to the drug cost.
The analysis was limited to those patients who had at least 1 pharmacy claim for a 90-day supply for any of the following therapeutic groups within the study period: antiasthmatics and bronchodilator agents, antidepressants, antidiabetics, antihyperlipidemics, antihypertensives, beta blockers, calcium channel blockers, diuretics, and thyroid agents. All drugs within each therapeutic group were included, regardless of dosage form. Therapeutic group was identified via the first 2 digits of the generic product identifier (GPI) associated with each pharmacy claim (respective GPI-2s: 44, 58, 27, 39, 36, 33, 34, 37, and 28). We limited our analysis to patients who were not new to therapy (identified by the presence of a prescription fill in the previous 6 months). Patients filling both 30-day and 90-day supplies for the same therapeutic group and those filling only 30-day supplies were excluded from this analysis. If a patient filled a prescription for more than 1 therapeutic group, they were included in each of the respective groups.
Patients were grouped based on the pharmacy channel used to obtain their 90-day supply of medication. Patients who exclusively used a retail pharmacy for a single therapeutic group were placed into the "Retail-90" group. Patients who exclusively used mail order services for a single therapeutic group were placed into the “Mail Order-90” group. Patients who used both mail order services and retail pharmacies for a single therapeutic group were excluded (n = 21,948) in order to eliminate any potential variation caused by using both channels. Patients filling prescriptions for 90-day supplies at retail for 1 therapeutic group, but filling 90-day prescriptions through mail order for a different therapeutic group, would be included in both the Retail-90 and the Mail Order-90 group for each respective therapeutic group. Construction of the study groups is shown in the Figure
We used the medication possession ratio (MPR) to calculate medication adherence for a 1-year period separately for each of the 9 therapeutic groups. MPR was calculated as the number of actual adherent days divided by 365, where actual adherent days is the total days’ supply of medication a patient had available in a 365-day period starting with the index date of the initial prescription filled for each therapeutic group. If a patient had any prescription refills beyond 365 days following the first fill, those prescriptions were excluded from the analysis. If a patient had a refill toward the end of the 365-day period, the number of days’ supply of that refill exceeding 365 days from the first fill was subtracted from the number of actual adherent days so that the maximum MPR could not exceed 100%. If a patient filled a prescription for more than 1 type of medication within a particular therapeutic group, then the days’ supplies of each medication were added together and divided by 365. In such cases, patients need not be adherent to every medication, as a single MPR was computed for all drugs within that particular class. Overall MPR represents the average MPR at the patient level. When a patient used medications from more than 1 therapeutic group, the group-specific MPRs were averaged to obtain a single MPR measure for that patient.
Risk scores were developed from national drug codes in the pharmacy claims records using the Medicaid Rx (MRX) model of the University of California, San Diego Chronic Illness and Disability Payment System (CDPS), version 5.2 (The Regents of the University of California). (MRX is a pharmacy-based risk assessment model originally designed for a Medicaid population. The MRX model assigns each member to 1 or more of 45 medical condition categories based on the prescription drugs used by each member and to 1 of 11 age/sex categories. Based on the medical conditions and age/sex categories, the model predicts the overall medical costs for each member. However, recalibration of the CDPS model was not performed in this study because relative risk scores are assigned within therapeutic groups and not across the entire population.)
Propensity score matching was then used to minimize differences between the Retail-90 and Mail Order-90 groups at the therapeutic group level in terms of age-sex and risk score bands. A logistic regression model was applied with outcome variables representing Retail-90 versus Mail Order-90 channel status and independent variables including multiple age-sex bands and pharmacy risk score bands. We used a sample matching algorithm of the propensity score based on a “greedy” algorithm.19
A 1-to-1 match was performed at the therapeutic group level for the Retail-90 group and for the Mail Order-90 group. The matching process yielded an equal number of patients in the Retail-90 group and Mail Order-90 group for each of the 9 therapeutic groups. Unmatched patients were excluded from the analysis. Table 1
shows characteristics of all patients (before matching), matched patients, and those who were left unmatched (excluded) through this process. Propensity score matching was performed using bands and not continuous variables. However, population characteristics for age, gender (percent male), and risk score for patients pre- and post-propensity score matching can be found in Appendix 1
. Results for X2
comparison between the groups for age-sex and risk bands can be seen in Appendix 2
. All statistical analyses were performed using SAS statistical software, version 9.1.3 (SAS Institute Inc, Cary, North Carolina).
Patients in the Retail-90 group used drugs from an average of 1.13 different therapeutic groups during the study period compared with 1.83 for patients in the Mail Order-90 group, resulting in 13,836 unique patients across the 9 therapeutic groups in the Retail-90 group and 8574 in the Mail Order-90 group (see Table 1). Before matching, the Retail-90 and Mail Order-90 groups had significant differences (at the P
<.0001 level) in age-sex and risk bands across each of the 9 therapeutic groups. After propensity score matching was applied, patients in the 2 groups were found to not have significant differences in terms of age-sex and risk bands (P
>.99 for all therapeutic groups).
Propensity score–matched results indicate that across the 9 therapeutic groups analyzed in this study, unique patients who chose to obtain 90-day supplies of medication through a retail pharmacy had an overall average adherence rate that was higher (77.0% vs 76.0%) than for patients who chose to use mail order pharmacy for 90-day prescription fulfillment. This overall MPR difference was statistically significant (P
= .0067). There were no significant differences in MPR (postmatching) between retail and mail order channels for the individual therapeutic groups evaluated in this study, except for antidiabetics (80.2% vs 83.1%). These results are shown in Table 2
Results by MPR range (<50%, 50%-79%, and >
80%) for the propensity score–matched therapeutic groups are presented in Table 3
In the aggregate, our findings show that adherence rates for patients who choose to fulfill 90-day prescriptions through retail pharmacies compare favorably to those of patients using mail order. This finding is representative of patients using prescription drugs in the 9 therapeutic groups studied and with propensitymatched characteristics shown in Table 1. However, this study finding is not necessarily representative of patients using drugs in other therapeutic groups or of a commercial population.
Many factors may impact levels of adherence for prescriptions filled through different dispensing channels, although additional research is needed to fully assess their significance.
Retail pharmacies have the added advantage of offering patients the opportunity to interact face-to-face with a pharmacist on-site, as well as immediate prescription fulfillment.
A face-to-face interaction with a pharmacist can provide the framework for building a trusting relationship between the patient and pharmacist. This can present the pharmacist with opportunities to counsel patients on the importance of adherence to medication therapy, as well as address any medication-related issues. Several published studies have demonstrated that pharmacist counseling and medication management improve adherence levels.20,21
Retail pharmacies can fill 90-day prescriptions quickly. Except for patients enrolled in automatic refill programs, patients who rely on mail order must anticipate several days’ delay in receipt and so must remember to reorder well before running out of medication. In addition, any increased processing time or delay in mail delivery could prevent the patient from receiving medication when needed, potentially jeopardizing adherence.
Our study showed antidiabetics were the only therapeutic group in which adherence was found to be higher in the Mail Order-90 channel compared with Retail-90. Other published studies have found improved adherence in mail order relative to retail pharmacy for particular therapeutic drug classes. With respect to antidiabetics, a study by Devine et al14
assessing adherence rates for patients switching from retail to mail order also demonstrated higher adherence through mail order. However, their study was not limited to prescriptions of 90-day quantities. A study done by Duru et al in a population enrolled in a fully integrated health system demonstrated that patients with diabetes receiving newly prescribed antidiabetics, antihypertensives, or antihyperlipidemics through mail order are more likely to be adherent compared with patients dispensed medications through a retail pharmacy.13
Patients who primarily used mail order in the Duru study were more likely to have a financial incentive to use mail order compared with patients who primarily employed community pharmacies. Unlike a significant fraction of benefit designs,22
Duru does not indicate that the former group was subject to mandatory mail order, which Liberman et al found to correlate with reduced persistence during the patient’s first year of therapy.23
Additional studies are needed to better understand factors which may contribute to this result.
Our study had several limitations. First, in addition to cost share, a variety of factors may affect a person’s decision to obtain 90-day prescriptions through retail versus mail order pharmacy (when that choice is available), as well as adherence to medication therapy. Factors not controlled for in this study which may affect a person’s choice of pharmacy for filling 90-day prescriptions include patient income, race, education, setting (urban, suburban, or rural), and distance from a retail pharmacy. We were unable to adjust our findings for motivation-driven patient self-selection of dispensing channel. Because this analysis used prescription claims to measure adherence, it is not possible to confirm whether filled prescriptions were taken as instructed, whether instructions remained unchanged, whether patients were instructed to use “pill splitting” to achieve a desired dosage, whether medication samples were obtained, or whether prescriptions were obtained through pharmacy “$4 generic” cash programs. Our method of risk scoring based on prescription claims may not fully capture comorbidity or severity of illness. We were unable to determine whether the patients in this study were enrolled in automatic refill dispensing programs, which may increase adherence.
On a propensity-matched basis, patients who fill maintenance prescriptions at retail have a statistically significantly higher MPR than patients who fill their prescriptions via mail. Although the study demonstrated statistical significance in adherence for retail compared with mail, these findings may or may not be clinically significant, which was beyond the scope of the current study. The retail setting may present advantages related to quality of care and patient convenience. However, additional studies are needed to better understand factors which may contribute to this result.
1. Ho PM, Rumsfeld JS, Masoudi FA, et al. Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus. Arch Intern Med. 2006;166(17):1836-1841.
2. Ho PM, Magid DJ, Shetterly SM, et al. Medication nonadherence is associated with a broad range of adverse outcomes in patients with coronary artery disease. Am Heart J. 2008;155(4):772-779.
3. Simpson SH, Eurich DT, Majumdar SR, et al. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ. 2006;333(7557):15.
4. Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2008;16(2):CD000011.
5. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487-497.
6. Sokol MC, McGuigan KA, Verbrugge RR, Epstein RS. Impact of medication adherence on hospitalization risk and healthcare cost. Med Care. 2005;43(6):521-530.
7. Balkrishnan R, Rajagopalan R, Camacho FT, Huston SA, Murray FT, Anderson RT. 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(11):2958-2971.
8. Kaiser Family Foundation. Prescription Drug Trends. http://www.kff.org/rxdrugs/upload/3057-08.pdf. Published May 2010. Accessed February16, 2011.
9. US 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 2100. http://www.census.gov/population/www/projections/natdet-D1A.html. Accessed June 10, 2009.
10. DeVol R, Bedroussian A. An unhealthy America: the economic burden of chronic disease—charting a new course to save lives and increase productivity and economic growth. http://www.milkeninstitute.org/healthreform/pdf/AnUnhealthyAmericaExecSumm.pdf. Published October 2007. Accessed February 16, 2010.
11. Horgan C, Goody B, Knapp D, Fitterman L. The role of mail service pharmacies. Health Aff (Millwood). 1990;9(3):66-74.
12. Carroll NV, Brusilovsky I, York B, Oscar R. Comparison of costs of community and mail service pharmacy. J Am Pharm Assoc. 2005;45(3):336-343.
13. Duru OK, Schmittdiel JA, Dyer WT, et al. Mail-order pharmacy use and adherence to diabetes-related medications. Am J Manag Care. 2010;16(1):33-40.
14. Devine S, Vlahiotis A, Sundar H. A comparison of diabetes medication adherence and healthcare costs in patients using mail order pharmacy and retail pharmacy. J Med Econ. 2010;13(2):203-211.
15. Edlin M. Retail pharmacies fill 90-day prescriptions to compete with mail. Managed Healthcare Executive. http://managedhealthcareexecutive. modernmedicine.com/mhe/Pharmacy Best Practices/Retailpharmacies-fill-90-day-prescriptions-to-com/ArticleStandard/Article/detail/314991. Accessed April 20, 2010.
16. Clark BE, Siracuse MV, Garis RI. A comparison of mail-service and retail community pharmacy claims in 5 prescription benefit plans. Res Social Adm Pharm. 2009;5(2):133-142.
17. US Department of Health and Human Services, Agency for Healthcare Research and Quality. 2010 National Healthcare Disparities Report. http://www.ahrq.go/qual/nhdr10/nhdr10.pdf. Published March 2011. Accessed June 27, 2011.
18. Choudhry NK, Fischer MA, Avorn J, et al. The implications of therapeutic complexity on adherence to cardiovascular medications. Arch Intern Med. 2011;171(9):814-822.
19. Parsons LS. Reducing bias in a propensity score matched-pair sample using greedy matching techniques. SAS Paper 214-26. http://www2.sas.com/proceedings/sugi26/p214-26.pdf. Accessed March 18, 2011.
20. Lee JK, Grace KA, Taylor AJ. Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and lowdensity lipoprotein cholesterol: a randomized controlled trial. JAMA. 2006;296(21):2563-2571.
21. Rubio-Valera M, Serrano-Blanco A, Magdalena-Belío J, et al. Effectiveness of pharmacist care in the improvement of adherence to antidepressants: a systematic review and meta-analysis. Ann Pharmacother. 2011;45(1):39-48.
22. Marlo K, Dan D, Lykens C. Large Employers’ 2011 Health Plan Design Changes. National Business Group on Health. www.businessgrouphealth. org/pdf /Plan%20Design%20Survey%20Report%20Public.pdf. Published August 2010. Accessed April 12, 2011.
23. Liberman JN, Hutchins DS, Shrank WH, Selzak J, Brennan TA. Adherence to medication under mandatory and voluntary mail benefit designs. http://www.ajmc.com/media/pdf/52dec9f026e5b9b479f8a86b6822b2ba.pdf. Am J Manag Care. 2011;17(7):e260-e269. Accessed August 19, 2011.
Author Affiliations: From Walgreen Co (NK, ID, CP, PM), Deerfield, IL; SCIOinspire (ER, TA, KEK), Farmington, CT.
Funding Source: Study was self-funded by Walgreen Co.
Author Disclosures: Drs Khandelwal and Pegus, Mr Duncan, and Ms Murphy are employees of Walgreen Co, the funder of this study. Dr Rubinstein reports receiving consultancies and payment for involvement in the preparation of this manuscript from Walgreen Co. Dr Ahmed reports receiving consultancies and payments for involvement in methodology/data analysis from Walgreen Co. Mr Kudrak reports payment for involvement in the preparation of this manuscript from Walgreen Co.
Authorship Information: Concept and design (NK, ID, TA, KEK); acquisition of data (NK); analysis and interpretation of data (NK, ER, TA, PM, KEK); drafting of the manuscript (NK, ID, ER, PM); critical revision of the manuscript for important intellectual content (ID, ER, TA, CP, PM, KEK); statistical analysis (TA, KEK); obtaining funding (CP, ID); administrative, technical, or logistic support (KEK); and supervision (CP).
Address correspondence to: Nikhil Khandelwal, PhD, BPharm,1415 Lake Cook Rd, MS #L444, Deerfield, IL 60015. E-mail: Nikhil.Khandelwal@walgreens.com.