Generic Drugs, Cost, and Medication Adherence

US Pharm. 2015;40(6)(Generic Drug suppl):14-19.

ABSTRACT: Medication adherence has been a long-standing problem plaguing the medical community. Adherence to medication regimens is a multifactorial problem. Thus, identifying solutions may be challenging. The concept of lowering patient out-of-pocket costs through tier/copay reduction and generic substitution has been studied as a means to improve adherence. This idea has been proposed as one probable solution to this complex problem. Although the evidence provides promising results for this and other methods, limitations do exist and should be accounted for. Additionally, other negative factors associated with generic medications such as patient perceptions or preferences and rising costs should also be taken into consideration.

Treatment of chronic illness traditionally includes long-term use of medication therapy.¹ Practitioners, healthcare systems, and payers are concerned with patient adherence to medication regimens, as they are fully aware that non-adherence can lead to preventable morbidity, mortality, and increased healthcare costs.^1-3 Estimates have shown that patients are on average 50% adherent to their medication regimens.⁴ Medication nonadherence is commonly defined as taking <80% of prescribed doses.⁵ Nonadherence will likely increase as the population continues to age and medication regimens become more complex.⁶ Medication adherence is a multifactorial problem, and barriers to adherence can be challenging and may be hard to overcome.

High medication cost, including high patient out-of-pocket drug costs, has been associated with reduced adherence.⁷ Researchers have proposed reducing patient out-of-pocket medication costs as a method to increase adherence and, as an indirect result, decrease overall healthcare costs.⁸ Generic substitution and tier reduction are two methods that can be used to reduce patients’ out-of-pocket drug cost. Clinical equivalency of generic drugs has been shown in numerous trials.^4,9 Thus, lowering patient out-of-pocket drug costs through these methods may improve adherence, increase clinical outcomes, and reduce overall healthcare costs.

Generic Medications

The consideration that decreasing patient out-of-pocket medication costs through generic substitution, thus increasing medication adherence, has been effectively demonstrated through numerous studies.^2,10,11 In a recent study, Gagne and colleagues identified drug cost as an easy modifiable factor that may improve patient adherence.² The objective of the research was to determine if medication adherence was improved in patients taking generic statins (lovastatin, pravastatin, or simvastatin) compared to patients taking brand-name statins. Furthermore, they wanted to determine if the improved medication adherence improved health outcomes. This was an observational, propensity score–matched, new-user cohort study of Medicare Part D beneficiaries. Hence, all participants in the study had a drug benefit plan.²

The primary outcome was adherence, which was captured using linked electronic data from medical and pharmacy claims. Adherence was measured as the portion of days covered by the index statin up to 1 year after the index prescription date. The primary clinical outcome was a composite of hospitalization for an acute coronary syndrome, stroke, or all-cause mortality. Adherence was reported as 77 % for patients on generic statins versus 71% in the brand-name statin group (P >.001). Additionally, the authors reported an 8% reduction for the clinical outcome in the generic statin group compared to the brand statin group. The authors concluded that adherence and clinical outcomes were improved with generic statins compared to brand-name statins.²

Briesacher et al conducted a large study that analyzed generic prescribing effects across five disease states (hypercholesterolemia, diabetes, hypertension, hypothyroidism, seizure disorders) in patients ≥18 years of age from 45 different employers.¹⁰ This study found that lower copayments were associated with modestly improved adherence in two out of five studied conditions (hypercholesterolemia and diabetes), decreased adherence in two conditions (hypertension and hypo-thyroidism), and no difference in one condition (seizure disorders). Although the study revealed conflicting data varying by disease state, the findings were consistent with improved adherence among all five disease states/conditions when copayments were eliminated or waived regardless of whether the drug was brand or generic.¹⁰

Hershman et al also demonstrated a correlation between generic medication, cost, and adherence with aromatase inhibitors used in the treatment of early-stage breast cancer.¹¹ The objective of the study was to investigate the change in adherence after the introduction of a generic aromatase inhibitor. The researchers concluded that higher prescription copayments were associated with nonadherence and discontinuation of the aromatase inhibitors. Moreover, they found that patients on brand-name aromatase inhibitors had a higher discontinuation rate and a lower adherence rate.¹¹

Tier Reductions

Numerous studies have consistently associated higher copayments with decreased medication adherence and use.^12-16 Many patients with prescription drug plans are enrolled in a tiered pharmacy benefit structure. In a tier-type structure, copayments are highest for non-preferred brand medications and lowest for generic medications.¹³ Consequently, the use of tier reduction as a method to decrease patient cost and improve adherence has been explored.

Chen and colleagues measured this concept through a retrospective cohort study.¹² The study was designed to determine if adherence was improved when brand-name atorvastatin and rosuvastatin were reduced from second-tier to first-tier drugs in Medicare Part D beneficiaries. Adherence was measured using proportion of days covered (PDC), showing a 5.9% increase in PDC after adjusting for patient characteristics. Findings concluded that tier reduction had a positive effect on adherence and that cost lowering may improve adherence.¹²

Furthermore, Shrank et al mirrored these findings by investigating adherence among Americans enrolled in a three-tier pharmacy benefit plan.¹³ The objective of the study was to determine if patients receiving generic or preferred branded medications for chronic disease management were more adherent compared to patients who received nonpreferred brand medications. Results indicated that patients initiated on preferred medications or generics achieved higher adherence than those on nonpreferred prescriptions.¹³

Doshi et al investigated the effects of increased copayments on medication adherence to lipid-lowering medications.¹⁷ The investigators compared adherence among three groups: veterans who were exempt from copayments, those who paid some copayments, and those who paid all of their copayments out-of-pocket. Copayments were increased from $3 to $7. The study was performed at the Philadelphia VA Medical Center and concluded that adherence to lipid-lowering medication was adversely affected in some participants because of increased copayments, including patients at high risk for coronary heart disease.¹⁷ Traditionally, tier structures have been used only with brand-name products, but with the rising cost of generic drugs, plans have begun to use the tier structure with generic medications to offset the rising costs.¹⁸ As a result, the concept of tier reduction can be used to lower patient out-of-pocket cost and improve adherence.

Limitations of the Evidence

Though data show a positive correlation between medication adherence and generic prescribing, there are several limitations to these studies. One limitation is that price sensitivity varies across specific populations; therefore, these findings cannot be applied to all groups. Many studies that proved increased adherence with the use of generic medications and/or tier reduction only included study participants from Medicaid, Medicare, and VA populations.^2,10,12,17 Patient-specific factors may have also biased results showing a positive benefit. For example, these conclusions may not be projected to all disease states and conditions. Each study investigated specific drugs correlated to specific conditions (e.g., diabetes, hypertension, hyperlipidemia). Also, one study even showed opposing results based upon the disease state.¹⁰ Consequently, the evidence cannot be extrapolated to all patient populations.

Finally, questions arise as to how medication adherence can be accurately assessed. Finding the most accurate measurement for assessment can be difficult. In the studies previously discussed, the majority analyzed data through PDC or medication possession ratio (MPR), with >80% equaling adherence.^{2,10-12,17,19} These methods obtain data from prescription records and pharmacy claims. As a result, the investigators did not have access to, nor did they analyze, real-life adherence trends carried out by the study participants. 

Patient Perceptions/Preferences of Generic Medications

Contrary to evidence that generic substitution increases adherence, in some cases it will deter patients from continuing therapy and may have a negative effect on adherence. Consumers commonly have a misconception that brand-name medications are superior to generics and have expressed concern about the effects of generics.²⁰ This conviction of superiority compounded by difficulty in obtaining brand-name drugs because of insurance company rules, may result in poor adherence or discontinuation of medications. Additionally, a large number of editorials advise against the interchangeability of generic drugs, especially in narrow therapeutic index (NTI) drugs.⁴ As a result, this anecdotal information has appeared in the press, perpetuating the misconception.

Kesselheim and colleagues completed a systematic review of 47 studies that compared generic and brand-name cardiovascular drugs using clinical efficacy and safety endpoints.⁴ The researchers concluded that the evidence does not support the idea that brand-name cardiovascular drugs are superior to generic drugs. Other concerns for the impact of generic substitution on adherence included the pitfalls of changing medication appearance. In two separate studies, Kesselheim et al demonstrated the negative impact of changes in pill colors and shapes on adherence among epileptic patients and in a subsequent study done on post–myocardial infarction (MI) patients.⁹ In both studies, persistence, defined as the time from initiation to discontinuation of therapy, was adversely affected in a statistically significant manner by change in pill color. Change in pill shape also led to a statistically significant difference in persistence for cardiovascular medications post MI.  Based on the aforementioned studies, it is imperative that prescribers and pharmacists alert patients to changes in generic medication appearance.⁹

Proper patient education has been demonstrated to increase patient acceptance of generic prescribing.¹⁹ Therefore, there is great need for pharmacists to educate patients on utilization of generic alternatives; inform patients that they contain the same active ingredient, hence are deemed chemically equivalent to their brand-name counterparts; and explain when changes in pill shape, color, and/or overall appearance occur.

Rising Costs of Generic Medications

In addition to pill appearance, it is important to consider the paradoxical rise in cost of generic medication in recent years. As older drugs lose their patents, and if a single manufacturer legally obtains a market monopoly for a particular agent, generic medication costs have been shown, in some instances, to increase in price as much as 5,233%, as was seen in the case of doxycycline (TABLE 1).¹⁸ Ironically, this may mean that select brand-name medications, especially those brand-name drugs that are part of a preferred-tiered pharmacy benefit formulary, may be more cost-effective than generic alternatives. All things considered, it behooves healthcare providers to emphasize patient education and adherence techniques and to continue the valuable research into factors impacting patient adherence regardless of whether a patient is prescribed a generic or brand-name drug.

Conclusion

Numerous studies have proven that medication adherence can be improved by reducing patient out-of-pocket costs. As previously discussed, cost reduction can be accomplished through generic substitution and tier/copay reduction. The cost savings derived through these methods can be substantial; however, healthcare providers need to consider whether or not switching to a generic alternative will truly offset the litany of factors affecting patient nonadherence. Although research exists to support improvements in adherence, some studies have found only modest benefit. It is imperative that healthcare providers understand the complexity of medication adherence and the limitations of the current evidence.

REFERENCES

1. Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc. 2011;86: 304-314.
2. Gagne JJ, Choudhry NK, Kesselheim AS, et al. Comparative effectiveness of generic and brand-name statins on patient outcomes: a cohort study. Ann Intern Med. 2014;161:400-407.
3. Choudhry NK, Fischer MA, Avorn JL, et al. The impact of reducing cardiovascular medication copayments on health spending and resource utilization. J Am Coll Cardiol. 2012;60:1817-1824.
4. Kesselheim AS, Misono AS, Lee JL, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008;300:2514-2526.
5. Nieuwlaat R, Wilczynski N, Navarro T, et al. Interventions for enhancing medication adherence. Cochrane Data System Rev. 2014;11:CD000011.
6. Gurwitz JH, Field TS, Harrold LR, et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA. 2003;289: 1107-1116.
7. Chernew ME, Shah MR, Wegh A, et al. Impact of decreasing copayments on medication adherence within a disease management environment. Health Affairs (Project Hope). 2008;27:103-112.
8. Chernew ME, Juster IA, Shah M, et al. Evidence that value-based insurance can be effective. Health Affairs (Project Hope). 2010;29:530-536.
9. Kesselheim AS, Misono AS, Shrank WH, et al. Variations in pill appearance of antiepileptic drugs and the risk of nonadherence. JAMA Intern Med. 2013;173: 202-208.
10. Briesacher BA, Andrade SE, Fouayzi H, Chan KA. Medication adherence and use of generic drug therapies. Am J Manag Care. 2009;15:450-456.
11. Hershman DL, Tsui J, Meyer J, et al. The change from brand-name to generic aromatase inhibitors and hormone therapy adherence for early-stage breast cancer. J Natl Cancer Instit. 2014;106(11):dju319.
12. Chen SY, Shah SN, Lee YC, et al. Moving branded statins to lowest copay tier improves patient adherence. Am J Manag Care. 2014;20:34-42.
13. Shrank WH, Hoang T, Ettner SL, et al. The implications of choice: prescribing generic or preferred pharmaceuticals improves medication adherence for chronic conditions. Arch Intern Med. 2006;166:332-337.
14. Gibson TB, Mark TL, Axelsen K, et al. Impact of statin copayments on adherence and medical care utilization and expenditures. Am J Manag Care. 2006;12:SP11-SP19.
15. Gibson TB, Mark TL, McGuigan KA, et al. The effects of prescription drug copayments on statin adherence. Am J Manag Care. 2006;12:509-517.
16. Ye X, Gross CR, Schommer J, et al. Association between copayment and adherence to statin treatment initiated after coronary heart disease hospitalization: a longitudinal, retrospective, cohort study. Clin Therapeut. 2007;29:2748-2757.
17. Doshi JA, Zhu J, Lee BY, et al. Impact of a prescription copayment increase on lipid-lowering medication adherence in veterans. Circulation. 2009;119:390-397.
18. Kesselheim AS, Alpern JD, Stauffer WM. High-cost generic drugs—implications for patients and policymakers. N Engl J Med. 2014;371:1859-1862.
19. Van Wijk BL, Klungel OH, Heerdink ER, de Boer A. Generic substitution of antihypertensive drugs: does it affect adherence? Ann Pharmacother. 2006;40:15-20.
20. Shrank WH, Cox ER, Fischer MA, et al. Patients’ perceptions of generic medications. Health Affairs (Project Hope). 2009;28:546-556.

To comment on this article, contact rdavidson@uspharmacist.com.