Published January 19, 2018 MEDICATION MANAGEMENT Medication Adherence: The Elephant in the Room Jennifer Kim, PharmD, BCPS, BCACP, CPPAssistant Director of Pharmacy EducationArea Health Education Center, Greensboro, North CarolinaAssistant Professor of Clinical Education,University of North Carolina Eshelman School of PharmacyChapel Hill, North CarolinaClinical Pharmacist Practitioner, Cone Health Internal Medicine CenterGreensboro, North CarolinaKelsy Combs, PharmDPGY2 Ambulatory Care Pharmacy ResidentTriad HealthCare NetworkGreensboro, North CarolinaJonathan Downs, PharmDPharmacistWalgreens PharmacyMebane, North CarolinaFrank Tillman III, PharmD CandidateStudent PharmacistUniversity of North Carolina Eshelman School of PharmacyChapel Hill, North Carolina US Pharm. 2018;43(1)30-34.ABSTRACT: Medication adherence can have a more direct impact on patient outcomes than the specific treatment itself; it is estimated that adherence to chronic medications is about 50%. Maintaining a blame-free environment and providing patients with praise for goal achievement are essential for a trusting and effective pharmacist-patient relationship. Effective interventions include face-to-face counseling, mobile text messaging, simplifying medication regimens, using adherence packaging, minimizing adverse effects, helping with access, and engaging team members. Improving adherence can ultimately generate substantial clinical and financial rewards. According to the World Health Organization, medication adherence can have a more direct impact on patient outcomes than the specific treatment itself.1 Medication adherence can affect quality and length of life, health outcomes, and overall healthcare costs.2,3 Nonadherence can account for up to 50% of treatment failures, around 125,000 deaths, and up to 25% of hospitalizations each year in the United States. Typically, adherence rates of 80% or more are needed for optimal therapeutic efficacy. However, it is estimated that adherence to chronic medications is around 50%.3 Adherence rates can go down as time passes after the initial prescription is written, or as barriers emerge or multiply. The responsibility of medication adherence falls on patients and the ambulatory healthcare team. There is less consideration given to adherence in the hospital setting due to the ability to access, dispense, and administer medications on schedule while patients are hospitalized; however, medication adherence can be emphasized during transitions of care. Unfortunately, services to improve adherence are generally not reimbursed, so even in the outpatient setting, little incentive exists to improve this fundamental aspect of care. On the upside, quality-of-care models are evolving because of the recognized sequelae resulting from medication nonadherence.4-7 Approximately $100 to $300 billion in healthcare costs could be curtailed annually by addressing medication adherence.8 Addressing the Elephant in the Room Maintaining a blame-free environment and providing patients with praise for goal achievement are essential for a trusting and effective relationship between patient and practitioner.1 Patients may have challenges communicating adherence barriers to their healthcare team or have difficulty understanding the health consequences of nonadherence. Asking key questions through motivational interviewing is therefore imperative to revealing adherence challenges, and empathetic listening will assist in arriving at patient-centered solutions to overcome these challenges. Patient education and ongoing communication are critical for patient understanding and medication persistence, especially with mindful consideration that challenges can ebb and flow over time. In a retrospective cohort study, pharmacists provided face-to-face counseling to address adherence barriers to 3-hydroxy-3-methyl-glutaryl coenzyme A reductase agents (statins). Patients who received counseling (N = 586) were significantly more adherent at 12 months (P <.01, P <.05 comparing medication possession ratios 80%) and persistent with statin therapy at 120 and 365 days (P <.05 and P = .05, respectively).9 In another study of patients with type 2 diabetes, having more time with pharmacists and individualized education and adherence support, as well as female gender, were positively correlated with improved medication adherence.10 Studies of the Asheville Project, a quasiexperimental, longitudinal prepost cohort study set in 12 community pharmacies in Asheville, North Carolina, have modeled in-person pharmacist education to improve adherence, ultimately leading to improved clinical outcomes and reduced adverse events and costs.11-13 These outcomes were demonstrated for a variety of diseases including asthma, diabetes, hypertension, dyslipidemia, and cardiovascular disease. Effective Interventions Randomized controlled trials (RCTs) were reviewed to evaluate adherence-intervention models for patients with diabetes and cardiovascular disease.14 Overall, in-person models had similar efficacy to indirect ones (e.g., electronic, mailed, or faxed materials), with success rates of 56% and 52%, respectively. Of the in-person interventions, the face-to-face method was most successful (83%), followed by hospital discharge (67%), clinic-based interventions (47%), and phone calls (38%). Of the indirect interventions, electronic strategies (e.g., automated phone calls, electronic pill boxes, computer-generated targeted interventions) were more successful (67%) than paper (33%). This study suggests utility in investigating electronic and in-person strategies with patients, especially during approachable moments such as medication distribution and hospital discharge. Mobile text messaging is a key example of an electronic strategy worthy of further exploration. It is estimated that 77% of Americans own a smartphone, up from 35% in 2011.15 By demographics, around 92% of individuals aged 18 to 29 years; 42% of those aged 65 years or older; 89% of college graduates; 54% of those with less than a high school degree; 93% with an income of $75,000 or more; and 64% with an income of less than $30,000 own a smartphone. Across all demographic groups, 80% or more own some type of cell phone. In a meta-analysis that analyzed different text-messaging designs that were studied in 16 RCTs (2,742 patients total), it was determined that text messaging doubled the odds of medication adherence (odds ratio 2.11; P <.001) and improved overall adherence rates by 17.8%.16 Half of the trials incorporated daily text messages, 31% were personalized, and 63% were managed by computer programs. Overall, text messaging appears to be a promising tool for promoting medication adherence. Switching maintenance medications to 90-day prescriptions and enrolling patients in automatic refill programs also appear to be favorable interventions. One study involved sending faxes to prescribers to request 90-day prescriptions and refill-reminder letters for patients with 30-day prescriptions for oral antihypertensive medications and statins.17 The response rate from prescribers was 54%, and the approval rate for 90-day refills was 47%. Adherence increased by 2% (P <.001) for antihypertensive medications (ratio of odds ratio [ROR] = 1.334; 95% CI = 1.203-1.479) and 1.8% (P <.001) for statins. The odds of achieving adherence were greater in the intervention group for both antihypertensive medications and statins (ROR = 1.247; 95% CI = 1.132-1.374). There is general concern that automatic refill programs can lead to medication oversupply if not properly managed. One study showed that patients enrolled in both 30-day and 90-day automatic refill programs had significantly higher adherence, with adjusted differences across all classes of medications of 3% and 1.4%, respectively (P <.001).18 Patients enrolled in the automatic refill program also had significantly fewer days of oversupply compared with the control group (P <.001). Automatic refills and 90-day prescriptions are perhaps more suitable for patients challenged in picking up medications from the pharmacy on time (e.g., trouble remembering, lack of transportation). Other ways to improve patient-centered care (Table 1) and thus improve medication adherence include simplifying regimens, using pill boxes or packaging designed to improve adherence, and minimizing adverse effects.19 Further research is needed to provide more insight around a variety of patient-centered adherence interventions. Examples that may be valuable for research include home delivery, incorporating family and team members, involving students or residents, and creating roles for pharmacy technicians. Engaging Team Members Community pharmacists are well-positioned to interact with prescribers because of access to prescription histories and the ability to monitor and intervene based on adherence findings. Recommendation acceptance rates in the community setting range from 42% to 60%.20 One of the key factors affecting these acceptance rates is pharmacist accessibility to the clinical team. In clinical settings where recommendation acceptance rates are around 70% to 90%, pharmacists may interact more with team members, which can optimize acceptance of interventions.21,22 In the community pharmacy setting, many interventions are completed via telephone or fax, and access to patient health records is usually limited. Recommendation acceptance rates may be enhanced by optimizing communication. Prescribers were surveyed to identify characteristics of an ideal fax template, which may help to increase provider response rates to community pharmacist recommendations. Findings suggested that the ideal fax template would include only essential information for the prescriber, going beyond stating that a patient is nonadherent and including a concise description of barriers with an action plan to increase adherence.23 This same strategy can be applied during other types of pharmacist-prescriber interactions including face-to-face, telephone, or electronic messaging. One example of a clinic-based pharmacist program and its impact on adherence included high-risk cardiac patients at several U.S. Veterans Affairs Medical Centers.24 This RCT involved a multifaceted 1-year intervention following hospital discharge for acute coronary syndromes. Ambulatory and inpatient pharmacists participated in posthospital transitions of care, and services included pharmacist-led medication reconciliation and synchronization (within 7-10 days of hospital discharge), pharmacist-provided patient education, collaboration between pharmacists and primary care clinicians and/or cardiologists, pharmacist educational voice messaging and telephone calls, and medication-refill reminder calls. Significantly higher adherence was apparent in the collaborative intervention group compared with usual care (89.3% vs. 73.9%, P = .003). There was also more adherence to clopidogrel (P <.001), statins (P <.001), and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (P = .03). What’s in It for Me? Buy-in from the healthcare team and administrators is also essential for success with medication adherence endeavors.25 Financial incentives can motivate patients to improve adherence and also engage prescribers, as shown in one RCT. Statin adherence rates were higher in the group that provided incentives to both patients and physicians (39% vs. 27%, P <.001), as well as in the patient-only incentive group (34% vs. 27%, P = .01), compared with the control group. However, the physician-only incentives group did not show improved adherence. Only the combined patient and physician incentives group demonstrated significantly improved clinical goals, demonstrated by more pronounced LDL-C reductions (33.6 vs. 25.1, P = .002), more patients achieving their LDL-C goals (49% vs. 36%, P = .003), and more patients receiving medication intensification (38% vs. 27%, P = .004), compared with the control group. Improved clinical outcomes were not seen in the groups that only incentivized either patients or physicians. Patients were followed for up to 15 months in the study, highlighting the importance of ongoing follow-up and adherence support. Reducing drug costs can serve as an incentive to improve adherence. Prescription medication expenses comprise approximately 17% of personal healthcare services, and U.S. per-capita drug spending exceeds all other countries.26 In the U.S., payers are restricted from price negotiations with manufacturers; there are no regulations requiring manufacturers to charge below a consumer price index, as there are in Canada. Brand-name medications maintain market exclusivity for 12 to 15 years and are costly. Furthermore, high prices are often sustained once generic medications become available. Many generic medication prices have increased by 400% from 2012 to 2015.26,27 Additional efforts need to be made to help patients with drug costs in order to support medication adherence and positive patient health outcomes. Fortunately, pharmacists can use a variety of methods to help patients navigate low-cost or even free medication access.28,29 One hospital invested $5 million into free or reduced-cost medications for uninsured patients, distributed according to their federal poverty-level status.30 The hospital utilized its federal 340B drug discount-pricing program to provide medications at discharge and then continued refilling medications for these patients. Part of the revenue was invested in a medication-management program for this population. The medication-management program helped patients to better understand and stay on their medications, stay out of the hospital, and improve their health. The hospital reaped $12 million in savings owing to a reduction in emergency room visits and hospitalizations. Pharmacists are becoming increasingly involved in pay-for-performance initiatives, and payers are now offering opportunities specific to medication adherence.31-34 Through these programs, pharmacists can utilize a variety of strategies to improve medication-adherence metric performance, obtain remuneration for services, and be credited for clinical outcomes resulting from improved medication adherence. Additionally, improving medication adherence can increase revenue for pharmacies due to the increased numbers of prescriptions being filled on schedule. When pursuing medication adherence initiatives, pharmacists should maximize technology to detect nonadherence, facilitate communication and therapy changes, and document interventions. Pharmacists should also track data (adherence rates, clinical outcomes, revenue, cost savings, patient and team perceptions, etc.). Sharing these outcomes with patients can serve as positive reinforcement and help them understand the link to feeling healthier. Reporting outcomes can also justify services and motivate team members by illustrating the impact medication adherence can have on patient care. Potential cost savings or revenue generated by these adherence outcomes, as exemplified in the 340B program, can further promote buy-in from patients, team members, and the organization. Conclusion Medication adherence can have a tremendous impact on quality and length of life, health outcomes, and overall healthcare costs. Engaging patients and the healthcare team is essential to success in achieving medication adherence and persistence. Notable interventions include face-to-face counseling, electronic reminders, regimen simplification, adherence packaging, minimizing adverse effects, 90-day supplies, automatic refills, providing incentives or cost savings, and maintaining ongoing communication. 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