Currently Viewing:
The American Journal of Managed Care September 2016
Implications of Evolving Delivery System Reforms for Prostate Cancer Care
Brent K. Hollenbeck, MD, MS; Maggie J. Bierlein, MS; Samuel R. Kaufman, MS; Lindsey Herrel, MD; Ted A. Skolarus, MD, MPH; David C. Miller, MD, MPH; and Vahakn B. Shahinian, MD
New Strategies for Aligning Physicians With Health System Incentives
Amol S. Navathe, MD, PhD; Aditi P. Sen, MA; Meredith B. Rosenthal, PhD; Robert M. Pearl, MD; Peter A. Ubel, MD; Ezekiel J. Emanuel, MD, PhD; Kevin G. Volpp, MD, PhD
Currently Reading
Cost-Benefit of Appointment-Based Medication Synchronization in Community Pharmacies
Julie A. Patterson, BS; David A. Holdford, PhD, MS, BSPharm; and Kunal Saxena, PhD, MS
The Opportunities and Challenges of the MSSP ACO Program: A Report From the Field
Farzad Mostashari, MD, ScM, and Travis Broome, MPH
Managing Inappropriate Requests of Laboratory Tests: From Detection to Monitoring
Maria Salinas, PhD; Maite López-Garrigós, PhD; Emilio Flores, PhD; Maria Leiva-Salinas, MD, PhD; Alberto Asencio, MD; Javier Lugo, MD; and Carlos Leiva-Salinas, MD, PhD
Measuring the Cost Implications of the Collaborative Accountable Care Initiative in Texas
Vivian Ho, PhD; Timothy K. Allen, PhD; Urie Kim, BBA; William P. Keenan, BA; Meei-Hsiang Ku-Goto, MA; and Mark Sanderson, PhD
Knowledge Gaps Inhibit Health IT Development for Coordinating Complex Patients' Care
Robert S. Rudin, PhD; Eric C. Schneider, MD, MSc; Zachary Predmore, BA; and Courtney A. Gidengil, MD, MPH
Mapping US Commercial Payers' Coverage Policies for Medical Interventions
James D. Chambers, PhD; Matthew D. Chenoweth, MPH; and Peter J. Neumann, ScD
Opportunities to Improve the Value of Outpatient Surgical Care
Feryal Erhun, PhD; Elizabeth Malcolm, MD, MSHS; Maziyar Kalani, MD; Kimberly Brayton, MD, JD, MS; Christine Nguyen, MD, MS; Steven M. Asch, MD, MPH; Terry Platchek, MD; and Arnold Milstein, MD, MPH

Cost-Benefit of Appointment-Based Medication Synchronization in Community Pharmacies

Julie A. Patterson, BS; David A. Holdford, PhD, MS, BSPharm; and Kunal Saxena, PhD, MS
This study conducted a cost-benefit analysis of appointment-based medication synchronization for improving adherence in patients on chronic medications for hypertension, hyperlipidemia, and diabetes.
In sensitivity analyses, the benefit-cost ratio of ABMS was most sensitive to drug prices (Table 5). As drug prices were lowered to VA pricing, estimated savings per additional dollar spent on medications ranged from $40 to $301. Favorable cost-benefit findings were robust for metformin, statins, and BBs. Cost-benefit was no longer favorable for thiazides at a drug price of AWP – 50%, ACE inhibitors/ARBs at AWP – 30%, and DCCBs at AWP. With the introduction of patient cost sharing through a $10 co-pay, benefit-cost ratios increased from 3.8 to 1 up to 59 to 1, depending on the drug class and assuming that co-pays did not reduce medication adherence. Cost-benefit was robust to changes in medical costs and ABMS effectiveness; however, with the introduction of payer reimbursements for ABMS, benefit-cost ratios remained favorable only for metformin and statins.



This study quantifies the cost-benefit of an ABMS model to improve adherence among patients prescribed chronic medications. Previously studied interventions to improve nonadherence often lack reliable effectiveness or contribute to higher overall costs to a payer or provider. ABMS has a demonstrated impact on improving adherence and persistence to chronic medications,27,28 which can increase annual medication costs to a payer on account of increased annual medication refills. This study calculated the overall disease-related healthcare savings attributed to improved adherence due to ABMS and analyzed the cost-benefit of ABMS compared with standard pharmacy dispensing from a payer perspective.

Few studies have used cost-benefit analyses to model the costs and outcomes of community pharmacy-based adherence interventions, and even fewer have taken a payer perspective.38,39 This study found that, due to improved adherence with ABMS, the disease-related medical savings per additional dollar spent on medications ranged from $1.25 to nearly $37 for 6 classes of chronic medications. These results suggest that payer partnerships with pharmacies offering ABMS are cost-beneficial and provide a positive return on investment.

ABMS works within the existing framework of medication dispensing in a community pharmacy setting to emphasize proactive medication management and consistent patient–provider communication. Because it can be incorporated into a pharmacy workflow, the nondrug cost of ABMS programs is minimal to the pharmacy and is provided free of charge to patients and payers. The combined low cost and high effectiveness of ABMS promotes more favorable cost-benefit ratios than expensive, but effective, educational and management interventions40 and low-cost, but less effective, electronic and reminder interventions.41 

The addition of pharmacist compensation to ABMS programs was not justified in this economic model. Annual per-patient fees were not made up by medical savings of negative health consequences, although the results might change for populations who are at greater risk of chronic illnesses or if the analysis looked at a time period longer than 1 year. Furthermore, this analysis was limited to separate analyses for each medication class, when patients with diabetes and hypertension take, on average, 4.1 and 1.7 disease-related prescriptions, respectively.42,43

The widespread implementation of ABMS faces a number of barriers. Pharmacy benefit managers (PBMs) may not be incentivized to support ABMS under some business models. Additionally, ABMS would not benefit PBMs whose performance is measured solely on medication cost, as medication costs increase with improved adherence. Here, the disease-specific medical savings would show up on the income statements of other payers. PBM disincentives might also exist for ABMS programs offered by pharmacies that are out-of-network. ABMS programs might hinder PBM efforts to shift dispensing to mail order services or influence terms of contract for rebates. 



This research included several limitations. The adherence data was collected from the implementation of ABMS in a small pharmacy chain offering services within a limited geography in Ohio. The impact of ABMS on adherence may not be duplicated for other populations in other settings, although ABMS programs offered by other pharmacies in different geographic locations have shown similar effectiveness.26,27 

This study used data that reported associations between ABMS programs and adherence. The participants in the ABMS program opted into the program, which may have made them more likely or motivated to adhere to their medications. Matching ABMS patients to control patients based on prior adherence behavior and demographics aimed to minimize this potential bias. The analysis also did not control for other potential influences on medication adherence, including socioeconomic and insurance status, regimen complexity, and patient health status. Although increasing and decreasing the effectiveness of ABMS by 20% in sensitivity analyses did not substantially change the benefit-cost ratios, the impact of unmeasured confounders and self-selection bias on the association between ABMS programs and adherence is not known.

Finally, this study used data that reported associations between medication adherence and disease-related costs based on the findings of an observational study, and the design of that study has important limitations.5 In their study of the association between medication adherence and healthcare costs, Sokol et al adjusted for demographic and health status variables, but the impact of prior adherence behavior and the healthy adherer effect on their findings is not known. These potential confounders may have biased the results of their observational study toward overestimating the association between improved adherence and lower healthcare costs. However, compared to a study by Roebuck et al,6 which employed more rigorous linear fixed-effects modeling to account for the endogeneity of adherence, the Sokol et al study reports smaller decreases in healthcare costs associated with improved adherence. Beyond providing a more conservative estimate of the association between adherence and medical costs compared with that reported by Roebuck et al, the use of data from the study by Sokol et al in this model provided the opportunity to consider in the cost-benefit model the prescription and medical costs associated with 5, rather than 2, adherence categories.

Additionally, disease-related costs by adherence level were reported over a 1-year time frame. The conditions studied—diabetes, hypertension, and hyperlipidemia—are chronic in nature and are linked to long-term sequelae, including myocardial infarction, stroke, and kidney disease. The limited 1-year time frame utilized in this study may have underestimated the impact of ABMS on long-term adverse health events associated with nonadherence in chronic conditions.

Future Research

This research reports the cost-benefit of a synchronization and appointment-based program for 6 classes of chronic medications. The adherence data for patients with ABMS-based care and usual dispensing practices were linked to previously published, claims-based data reporting the disease-specific medical costs associated with 5 levels of adherence. The direct effect of synchronization, as it relates to patient outcomes and costs, has not been reported. Future research is needed to explore the impact of ABMS on adherence, costs, and outcomes in the same population.

The cost-benefit of maintaining an ABMS program from a pharmacy perspective should also be explored. Synchronization may improve control of medication inventory and efficient personnel scheduling. Improved adherence may also result in increased refill revenue. The impact of ABMS on front-end sales is unknown. ABMS may improve patient loyalty, but it may also reduce up-front sales due to fewer monthly pharmacy visits.

Additional research could focus on expanding ABMS programs to include other chronic disease states, including chronic obstructive pulmonary disease44 and asthma,45 for which other adherence interventions have shown cost-beneficial results. Previously documented interventions have had limited impact on adherence to medications for depression,46 which has been associated with significant increases in medical service utilization47; however, improved adherence may not reduce utilization.48 The cost-benefit of ABMS for depression is not known.

A recent clinical and economic analysis of the use of liraglutide in the treatment of type 2 diabetes concluded that adherent and persistent patients recorded higher total healthcare costs driven by higher pharmacy costs.49 This current study focused on the impact of ABMS on adherence to predominately generic oral medication classes. In these cases, an increase in medication usage confers minimal additional cost; expanding the use of injectable and biologic medications for chronic conditions may impact the benefit-cost ratios by substantially increasing the costs associated with improved adherence. Future research may focus on the cost-benefit of ABMS with more expensive drug classes.


To our knowledge, this is the first study to evaluate the cost-benefit of ABMS in community pharmacies. The results indicated that ABMS offers payers a positive return on investment. Although further research is needed to evaluate the long-term costs and outcomes of ABMS, payer partnerships with pharmacies offering ABMS may improve patient outcomes in a cost-beneficial manner.

Author Affiliations: Department of Pharmacotherapy and Outcomes Sciences, Virginia Commonwealth University School of Pharmacy (JAP, DAH, KS), Richmond, VA.

Source of Funding: None.

Author Disclosures: The authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (DAH, JAP); acquisition of data (DAH, KS); analysis and interpretation of data (JAP, KS); drafting of the manuscript (JAP); critical revision of the manuscript for important intellectual content (DAH, KS); statistical analysis (JAP); provision of patients or study materials (DAH); and supervision (DAH).

Address Correspondence to: David A. Holdford, BSPharm, MS, PhD, Virginia Commonwealth University School of Pharmacy, Department of Pharmacotherapy and Outcomes Sciences, McGuire Hall, Room 213, PO Box 980533, 1112 East Clay St, Richmond, VA 23298-0533. E-mail:

1. 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. doi: 10.1016/j.ahj.2007.12.011.

2. Ho PM, Bryson CL, Rumsfeld JS. Medication adherence: its importance in cardiovascular outcomes. Circulation. 2009;119(23):3028-3035. doi: 10.1161/CIRCULATIONAHA.108.768986.

3. DiMatteo MR, Giordani PJ, Lepper HS, Croghan TW. Patient adherence and medical treatment outcomes: a meta-analysis. Med Care. 2002;40(9):794-811. doi: 10.1097/01.MLR.0000024612.61915.2D.

4. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487-497. doi: 10.1056/NEJMra050100.

5. 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. doi: 00005650-200506000-00002.

6. Roebuck MC, Liberman JN, Gemmill-Toyama M, Brennan TA. Medication adherence leads to lower health care use and costs despite increased drug spending. Health Aff (Millwood). 2011;30(1):91-99. doi: 10.1377/hlthaff.2009.1087.

7. Dragomir A, Côté R, Roy L, et al. Impact of adherence to antihypertensive agents on clinical outcomes and hospitalization costs. Med Care. 2010;48(5):418-425. doi: 10.1097/MLR.0b013e3181d567bd.

8. De Vera MA, Bhole V, Burns LC, Lacaille D. Impact of statin adherence on cardiovascular disease and mortality outcomes: a systematic review. Br J Clin Pharmacol. 2014;78(4):684-698.

9. Stuart BC, Dai M, Xu J, E Loh FH, S Dougherty J. Does good medication adherence really save payers money? Med Care. 2015;53(6):517-523. doi: 10.1097/MLR.0000000000000360.

10. Yeaw J, Benner JS, Walt JG, Sian S, Smith DB. Comparing adherence and persistence across 6 chronic medication classes. J Manag Care Pharm. 2009;15(9):728-740. doi: 10.18553/jmcp.2009.15.9.728.

11. Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA. 2002;288(4):462-467.

12. Benner JS, Glynn RJ, Mogun H, Neumann PJ, Weinstein MC, Avorn J. Long-term persistence in use of statin therapy in elderly patients. JAMA. 2002;288(4):455-461.

13. Benner JS, Chapman RH, Petrilla AA, Tang SS, Rosenberg N, Schwartz JS. Association between prescription burden and medication adherence in patients initiating antihypertensive and lipid-lowering therapy. Am J Health Syst Pharm. 2009;66(16):1471-1477. doi: 10.2146/ajhp080238.

14. An J, Nichol MB. Multiple medication adherence and its effect on clinical outcomes among patients with comorbid type 2 diabetes and hypertension. Med Care. 2013;51(10):879-887. doi: 10.1097/MLR.0b013e31829fa8ed.

15. Cramer JA, Benedict A, Muszbek N, Keskinaslan A, Khan ZM. The significance of compliance and persistence in the treatment of diabetes, hypertension and dyslipidaemia: a review. Int J Clin Pract. 2008;62(1):76-87. doi: 10.1111/j.1742-1241.2007.01630.x.

16. Krueger KP, Berger BA, Felkey B. Medication adherence and persistence: a comprehensive review. Adv Ther. 2005;22(4):313-356.

17. Krueger KP, Felkey BG, Berger BA. Improving adherence and persistence: a review and assessment of interventions and description of steps toward a national adherence initiative. J Am Pharm Assoc (2003). 2003;43(6):668-678; quiz 678-679.

18. Nieuwlaat R, Wilczynski N, Navarro T, et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2014;(11):CD000011. doi: 10.1002/14651858.CD000011.pub4.

19. Sapkota S, Brien JA, Greenfield J, Aslani P. A systematic review of interventions addressing adherence to anti-diabetic medications in patients with type 2 diabetes—impact on adherence. PLoS One. 2015;10(2):e0118296. doi: 10.1371/journal.pone.0118296.

20. McDonald HP, Garg AX, Haynes RB. Interventions to enhance patient adherence to medication prescriptions: scientific review. JAMA. 2002;288(22):2868-2879.

21. Cutrona SL, Choudhry NK, Fischer MA, et al. Modes of delivery for interventions to improve cardiovascular medication adherence. Am J Manag Care. 2010;16(12):929-942.

22. Green BB, Cook AJ, Ralston JD, et al. Effectiveness of home blood pressure monitoring, web communication, and pharmacist care on hypertension control: a randomized controlled trial. JAMA. 2008;299(24):2857-2867. doi: 10.1001/jama.299.24.2857.

23. Shore S, Ho PM, Lambert-Kerzner A, et al. Site-level variation in and practices associated with dabigatran adherence. JAMA. 2015;313(14):1443-1450. doi: 10.1001/jama.2015.2761.

24. Van Wijk BL, Klungel OH, Heerdink ER, de Boer A. Effectiveness of interventions by community pharmacists to improve patient adherence to chronic medication: a systematic review. Ann Pharmacother. 2005;39(2):319-328. doi: 10.1345/aph.1E027.

25. Viswanathan M, Kahwati LC, Golin CE, et al. Medication therapy management interventions in outpatient settings: a systematic review and meta-analysis. JAMA Intern Med. 2015;175(1):76-87. doi: 10.1001/jamainternmed.2014.5841.

26. Pharmacy’s appointment based model: a prescription synchronization program that improves adherence. APhA Foundation website. Published 2013. Accessed August 2016.

27. Holdford DA, Inocencio TJ. Adherence and persistence associated with an appointment-based medication synchronization program. J Am Pharm Assoc (2003). 2013;53(6):576-583. doi: 10.1331/JAPhA.2013.13082.

28. Holdford D Saxena K. Impact of appointment-based medication synchronization on existing users of chronic medications. J Manag Care Spec Pharm. 2015;21(8):662-669.

29. Straand J, Rokstad KS. Elderly patients in general practice: diagnoses, drugs and inappropriate prescriptions. a report from the More & Romsdal Prescription Study. Fam Pract. 1999;16(4):380-388.

30. Bartholow M. Top 200 drugs of 2012. Pharmacy Times website. Published July 17, 2013. Accessed April 13, 2015.

31. Lexi-Drugs. Lexicomp Online website. Accessed April 15, 2015.

32. Anderson BN, Cosway R. Effective contracting with pharmacy benefit managers: protecting a plan sponsor’s resources. Health Watch. 2010:22-27. Accessed April 13, 2015.

33. Calabrese D. Comparing pharmacy benefit managers: moving well beyond the simple spreadsheet analysis. Am Health Drug Benefits. 2008;1(5):9-19.

34. Medicaid drug price comparisons: average manufacturer price to published prices. Department of Health and Human Services Office of the Inspector General website. Published June 2005. Accessed April 13, 2015.

35. Consumer Price Index - all urban consumers [medical care]. Bureau of Labor Statistics website. Accessed April 13, 2015.

36. Pharmaceutical catalog search. US Department of Veterans Affairs, National Acquisition Center (CCST) website. Accessed April 13, 2015.

37. 2014 Employer Health Benefits Survey. Kaiser Family Foundation website. Published September 10, 2014. Accessed April 30, 2015.

38. Touchette DR, Doloresco F, Suda KJ, et al. Economic evaluations of clinical pharmacy services: 2006-2010. Pharmacotherapy. 2014;34(8):771-793. doi: 10.1002/phar.1414.

39. Perez A, Doloresco F, Hoffman JM, et al; American College of Clinical Pharmacy. ACCP: economic evaluations of clinical pharmacy services: 2001-2005. Pharmacotherapy. 2009;29(1):128. doi: 10.1592/phco.29.1.128.

40. Monson R, Bond CA, Schuna A. Role of the clinical pharmacist in improving drug therapy. clinical pharmacists in outpatient therapy. Arch Intern Med. 1981;141(11):1441-1444.

41. Checchi KD, Huybrechts KF, Avorn J, Kesselheim AS. Electronic medication packaging devices and medication adherence: a systematic review. JAMA. 2014;312(12):1237-1247. doi: 10.1001/jama.2014.10059.

42. Grant RW, Devita NG, Singer DE, Meigs JB. Polypharmacy and medication adherence in patients with type 2 diabetes. Diabetes Care. 2003;26(5):1408-1412.

43. Siegel D, Lopez J, Meier J. Antihypertensive medication adherence in the Department of Veterans Affairs. Am J Med. 2007;120(1):26-32. doi: 10.1016/j.amjmed.2006.06.028.

44. van Boven JF, Tommelein E, Boussery K, et al. Improving inhaler adherence in patients with chronic obstructive pulmonary disease: a cost-effectiveness analysis. Respir Res. 2014;15:66. doi: 10.1186/1465-9921-15-66.

45. Taitel MS, Kotses H, Bernstein IL, Bernstein DI, Creer TL. A self-management program for adult asthma. part II: cost-benefit analysis. J Allergy Clin Immunol. 1995;95(3):672-676.

46. Bosmans JE, Brook OH, van Hout HP, et al. Cost effectiveness of a pharmacy-based coaching programme to improve adherence to antidepressants. Pharmacoeconomics. 2007;25(1):25-37.

47. de Boer AG, Wijker W, de Haes HC. Predictors of health care utilization in the chronically ill: a review of the literature. Health Policy. 1997;42(2):101-115.

48. Reid KJ, Aguilar KM, Thompson E, Miller RM. Value-based benefit design to improve medication adherence for employees with anxiety or depression. Am Health Drug Benefits. 2015;8(5):263-271.

49. Buysman EK, Liu F, Hammer M, Langer J. Impact of medication adherence and persistence on clinical and economic outcomes in patients with type 2 diabetes treated with liraglutide: a retrospective cohort study. Adv Ther. 2015;32(4):341-355. doi: 10.1007/s12325-015-0199-z.

50. Pharmacy Healthcare Solutions, Inc. Medication therapy management programs: are they going as planned? AMCP website. Published June 20, 2008. Accessed April 30, 2015. 
Copyright AJMC 2006-2020 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
Welcome the the new and improved, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up