Improving Adherence to Therapy and Clinical Outcomes While Containing Costs: Opportunities From the Greater Use of Generic Medications: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians

Per capita spending in the United States is higher than in any other country without correspondingly high performance on many measures of health care quality (1). Efforts to maximize the value of our health care dollars have focused on situations where expensive therapies are used when less costly, equally effective options are available. The underuse of generic medications is an important example. Prescription drugs now account for more than $325 billion in annual spending in the United States (2) and play a central role in the management of chronic disease, yet physicians and other providers frequently treat patients with more expensive brand-name products even when equally effective, well-proven, and less expensive generic therapies are available (3). The purpose of this article is to help guide internists and other clinicians in making high-value, cost-conscious decisions about the use of generic drugs. This review sought to address 5 questions: 1) How commonly are brand-name medications used when a generic version is available? 2) How does the use of generic medications influence adherence? 3) What is the evidence that brand-name and generic medications have similar clinical effects? 4) What are the barriers to increasing the use of generic medications? 5) What strategies can be used to promote cost savings through greater generic medication use? Methods The research presented was identified with a Google Scholar literature search conducted in 2015. For each of the 5 questions, 5 key articles that provided high-quality, relevant data (see the Appendix Table) were identified with input from 3 other investigators who had conducted research on generic medications (see the Acknowledgment). For each key article, 100 related articles were identified by using this functionality in Google Scholar, resulting in a total of 2500 potentially relevant citations that were reviewed. From these, articles were included if they provided original empirical data that were directly relevant to the key question; in addition, the reference lists of the selected articles were reviewed for other potentially relevant studies. Studies that did not provide empirical data or that reported only pharmacokinetic or pharmacodynamic differences between agents without any clinical outcome data were excluded. In addition, the follow-on versions of biologic drugs (biosimilars) were excluded from this review because of their clinical and regulatory complexity and the relatively limited evidence about their use. As such, this article is intended to provide practical advice based on the best available evidence about traditional small-molecule pharmaceuticals. Appendix Table. Key Articles Used to Perform the Literature Searches The target audience for this article is all clinicians, and the target patient population is all adults. This article was reviewed and approved by the American College of Physicians (ACP) Clinical Guidelines Committee. How Commonly Are Brand-Name Medications Used When a Generic Version Is Available? Although the use of generic drugs has increased over time (4), health care providers frequently prescribe brand-name medications when generic versions are available. For example, more than 40% of Medicare beneficiaries with cardiovascular disease in 2001 used brand-name angiotensin-converting enzyme inhibitors and calcium-channel blockers instead of molecularly identical generics (5). More recently, Gellad and colleagues (6) studied Medicare beneficiaries with diabetes in 2008 and found that the use of multisource brand-name drugs (brand-name products for which identical generic versions are available) accounted for 23% to 45% of their prescriptions, depending on the class. This rate was substantially higher than that observed among patients with diabetes receiving care in the Veterans Affairs (VA) system, which has a centrally managed formulary that promotes greater use of generics. Efforts to increase rates of generic substitution are believed to result in substantial cost savings (7). A study examining all prescriptions filled by a nationally representative sample of patients between 1997 and 2000 estimated that using identical generic versions of brand-name prescription drugs could reduce drug spending by $5.9 billion, although this analysis was based on average wholesale prices and did not account for discounts that manufacturers provide to payers, which would reduce the potential cost savings (8). A nonpeer-reviewed analysis of 2009 Medicaid drug expenditures highlighted substantial use of brand-name multisource prescription medications, leading to excess costs of $329 million annually in just 20 therapeutic classes (9). The opportunity for therapeutic interchange (the substitution of a similarly effective but less expensive chemical entity to treat the same condition) may represent an even greater potential for cost savings. For the management of common chronic conditions, physicians often choose medications that are newer and relatively expensive even when clinical practice guidelines recommend otherwise (10, 11). For example, Fischer and Avorn (11) assessed antihypertensive prescribing in a state pharmacy assistance program and estimated that physicians prescribed newer brand-name medications instead of thiazides (which were recommended by the then-current antihypertensive guidelines from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) approximately 40% of the time; guideline-consistent prescribing was estimated to save more than $1.2 billion annually. Similarly, Desai and associates' study of commercially insured patients with diabetes (12) found that 35% of patients initiating therapy with an oral hypoglycemic drug did not receive recommended initial therapy with metformin and that almost 10% of patients received a dipeptidyl peptidase-4 inhibitor, such as sitagliptin (Januvia [Merck]), as initial monotherapy. These patterns of care were estimated to result in more than $1100 of potentially avoidable health spending per patient per year. Of note, contraindications or other clinical factors may not have been adequately captured in the administrative claims data that were used in these studies; thus, they may have overestimated the actual financial implications of changing practice patterns. Nevertheless, these results are consistent with Gellad and colleagues' estimate that Medicare could save $1.4 billion for patients with diabetes alone if drug prescribing mirrored that in the VA system through an approach combining generic substitution and therapeutic interchange (6). A 2005 analysis of commercially insured persons in the United States produced by a large pharmacy benefits manager estimated the potential cost savings of therapeutic interchange to lower-cost, guideline-adherent therapies in just 8 medication classes to be more than $20 billion annually (13). To put this into context, $20 billion could provide Medicaid coverage for more than 3.6 million presently uninsured persons, under the assumption that Medicaid expansion under the Patient Protection and Affordable Care Act costs an average of $5440 per person per year (14). In situations where neither generic substitution nor therapeutic interchange is possible, the use of brand-name agents may be clinically appropriate. For example, until recently there was no molecularly identical nor therapeutically equivalent generic version of clopidogrel (Plavix [Bristol-Myers Squibb and Sanofi]), and although the use of ipratropium may be appropriate for some patients with chronic obstructive pulmonary disease, there is no long-acting generic alternative for tiotropium (Spiriva [Boehringer Ingelheim]). Some patients may idiosyncratically achieve less therapeutic response or have greater adverse effects from a generic agent, justifying a switch to the brand-name counterpart. How Does the Use of Generic Medications Influence Adherence? Higher out-of-pocket costs for patients have consistently been associated with lower rates of long-term medication adherence (15). For example, prescriptions for brand-name medications are almost twice as likely as those for generic therapies to be abandoned (that is, never picked up after being filled) (16). Thus, greater use of generic drugs could result in better long-term adherence to essential therapies. Because higher adherence is associated with lower downstream health care costs for chronic conditions, greater use of generic therapies could reduce overall health care costs by this mechanism in addition to its direct effects on drug costs (1719). Most, but not all (20), studies evaluating the use of a generic rather than a brand-name drug for the treatment of chronic disease show significantly higher long-term adherence after treatment initiation (2123). For example, Shrank and colleagues (21) evaluated commercially insured patients initiating therapy in 6 classes of long-term medications and found that those who began therapy with a generic medication had adherence rates that were 5 to 7 percentage points higher than among comparable patients initiating therapy with a brand-name drug. The observational nature of this study and the relatively limited adjustment for patient comorbidity make it possible that the results were at least partially attributable to unmeasured confounding. The most recent evidence came from Gagne and associates (24), who studied a cohort of more than 90000 Medicare beneficiaries initiating a statin and compared adherence and outcomes between patients initiating a generic statin and those who initiated a brand-name version of the same statin. Patients in the former group were 6% more adherent than those in the latter group. Although this study used propensity score matching to adjust for baseline differences in a large number of patient characteristics and compared patients initiating generic statins with those initiating brand-name