Healthcare delivery is a networked enterprise. The connections between providers, payers, and purchasers have a profound influence on the quality and value of care patients receive.

 American sociologist Mark Granovetter has developed a useful typology for understanding how these networks function: through strong and weak ties.

 Strong ties are relationships between individuals of the same group (eg families, friends, or colleagues) and are small, frequent, intimate, and durable. Weak ties represent the connections between individuals of different groups, and are distributed, sporadic, and often fleeting.

The value of strong ties is intuitive; such connections provide reliable structures for socialization and support. Granovetter argues that weak ties, although more nuanced, are just as important. By bridging different groups, weak ties provide exposure to new people and new ideas. For example, Granovetter’s research demonstrates that weak ties are more impactful than strong ties in helping individuals find new opportunities for employment.

 Ultimately, neither strong nor weak ties are categorically more important, nor is either a substitute for the other. Each has unique benefits, and the most effective individuals and organizations tend to operate in networks enriched by both.

Granovetter’s paradigm of strong and weak ties has important implications for healthcare delivery and the ways in which it is changing. If we consider strong ties as the connections between physicians in the same practice, provider group, or hospital, then weak ties are the connections between physicians across organizations, including former colleagues, classmates, or naturally occurring referral networks. As healthcare reform unfolds, the nature of these relationships is changing. For most of American medical history, weak ties have dominated physician networks. Individual and small-group practices were the norm. Physicians had admitting privileges at hospitals, but that was often where their formal connection to other providers and institutions ended. Amidst this climate, informal networks of physicians emerged, based more on shared patients and social connections than on market forces and payment structures.

Over the past 2 decades, network dynamics have shifted from weak to strong ties. Whereas the majority of physicians worked in physician-owned practices in the 1990s, today, most are employed by hospitals.

 The Affordable Care Act and related private-sector reforms have accelerated these trends, most notably, through the growth of accountable care organizations (ACOs) and continued consolidation in the care delivery market.

ACOs and other high-profile delivery system innovations have been designed to promote coordinated care. To achieve these aims, they create formal networks of physicians and strive to confine care delivery to small networks. New networks created under these models are often substantially different than the organic referral networks they replace.

 Confidence in the potential of ACOs is grounded in a belief in the power of strong ties and the added control they afford over healthcare utilization. Success is predicated on the notion that formal networks of providers will lead to more coordinated and effective care.

Although a shift toward strong ties promises benefits, there are unintended consequences to the concomitant abandonment of weak ties. A tremendous amount of learning, improvement, and innovation is needed to achieve the national goals of better care, better health, and lower costs. Physician networks are central conduits to these efforts—the means by which information on what works best in healthcare is created and shared.

 Optimal knowledge generation and dissemination requires a delicate balance between strong and weak ties.

Strong ties promote learning and diffusion within groups, whereas weak ties foster knowledge transfer between groups. As such, weak ties can help individuals acquire useful knowledge more rapidly, innovate swiftly, and nimbly respond to challenges—a pattern demonstrated empirically in healthcare and other industries.

 Efforts to improve the identification, adoption, and spread of new innovations and best practices will be hamstrung within physician networks dominated by strong ties. Even Granovetter observed that “social systems lacking in weak ties will be become fragmented and incoherent, new ideas will spread slowly, scientific endeavors will be handicapped.”

 Structuring away informal knowledge sharing networks has the potential to create insular nodes of practice, with poor communication among different organizations and groups of physicians.

This may be especially problematic for the care of patients who do not fit neatly into clinical guidelines. Whereas the creation and adoption of clinical guidelines is likely to be accelerated through strong ties, care for complicated patients necessitates weak ties. Physicians have historically managed these nuanced patients through informal consultations and referrals, tapping into networks of friends and colleagues forged during training and clinical practice. In doing so, they learn from the experiences of physicians within and outside of their organization, and adapt their practice accordingly. Within physician networks increasingly dominated by strong ties, these patients may be promptly whisked away to in-system specialists, often through automated referral protocols. Therefore, what is gained by stopping “leakage” is also a lost opportunity for systemwide learning.

Consolidation and strict affiliation risk the endurance of weak ties, as well as the natural innovation and learning that occurs through them. As care delivery models continue to evolve, it will be important to consider strategies to preserve, or reintroduce, weak ties among physicians. Learning networks can help bridge the gaps between clusters of strong ties, and increased clinical data sharing and reporting will allow physicians to see and learn how colleagues at other institutions provide care. Most important will be the need for payers and policy makers to design rules and regulations that, instead of promoting excessive consolidation, allow for independent physician groups to survive, and even thrive, in new delivery models.

Both strong and weak ties have their roles in the organization and structure of healthcare delivery—and the most effective and efficient models will recognize and accentuate the value created by each. Prevailing strategies for delivery reform focus on the power of strong ties by tightening and formalizing relationships among physicians and health systems. Ignoring the importance of weak ties will jeopardize the long-term success of these initiatives. Granovetter urged us to remember the strength of weak ties, so as health reform moves forward, it will behoove policy makers and health system leaders to do the same.

 Harvard Medical School (BWP), Boston, MA; Harvard School of Public Health (AKJ), Boston, MA; CareMore Health System (SHJ), Cerritos, CA; Stanford University School of Medicine (SHJ), Palo Alto, CA.

 Dr Jain is an employee of CareMore Health System. Mr Powers and Dr Jha report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

 Concept and design (BWP, SHJ); acquisition of data (BWP); analysis and interpretation of data (BWP, SHJ); drafting of the manuscript (BWP, SHJ); critical revision of the manuscript for important intellectual content (BWP, SHJ, AKJ); administrative, technical, or logistic support (BWP, SHJ, AKJ); and supervision (SHJ, AKJ).

 Sachin H. Jain, MD, MBA, CareMore Health System, 12900 Park Plaza Dr, Ste 150, Cerritos, CA 90703. E-mail: sachin.jain@caremore.com.

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Articles

COMMENTARY

New delivery models are altering the connections between physicians, which may lead to a decreased capacity for innovation and the slower spread of new ideas.

Remembering the Strength of Weak Ties

Specialty drugs often represent major medical advances for patients with few other effective options available, but high costs have attracted the attention of both payers and policy makers. We reviewed the evidence regarding the impact of cost sharing on utilization of specialty drugs indicated for rheumatoid arthritis (RA), multiple sclerosis (MS), and cancer, and on the use of nondrug medical services, health outcomes, and spending. 

Systematic review of Medline-indexed studies identified via an OVID search for articles published in English from 1995 to 2014, using combinations of terms for cost sharing and specialty drugs, and/or our 3 conditions of interest. We identified additional studies from reference lists.   

We identified 19 articles focusing on specialty drugs indicated for MS (n = 9), cancer (n = 8), and RA (n = 8). Studies examined prescription abandonment (n = 3), initiation or any utilization (n = 8), adherence (n = 9), persistence/discontinuation (n = 7), number of claims (n = 1), and drug spending (n = 1). Findings varied by disease, but generally indicated stronger effects for noninitiation or abandonment of a prescription at the pharmacy and somewhat smaller effects for refill behavior and drug spending once patients initiated therapy. Studies have not examined specialty tier cost sharing seen under Medicare Part D or health insurance exchanges, nor effects on medical utilization, spending, or health outcomes. 

Evidence to date generally indicates reductions in specialty drug utilization associated with higher cost sharing; effects have varied by type of disease and specialty drug use outcome. We draw upon our findings and the gaps in evidence to summarize future directions for research and policy.

	Current evidence indicates that higher specialty drug cost sharing is associated with reduced specialty drug utilization. Research examining broader health outcomes and spending is unavailable. 

		Cost-sharing effects varied by type of disease and specialty drug utilization outcome examined. 

		There is a critical need for methodologically rigorous research to further evaluate whether the aggressive cost-sharing arrangements found in the current marketplace may cause patients to forego, delay, or decrease adherence to specialty drugs, and whether that results in poor health outcomes and higher total spending.

Specialty drugs typically represent significant medical advances, either in the form of novel approaches for the treatment of complex chronic conditions (eg, rheumatoid arthritis [RA], multiple sclerosis [MS]) or because they target diseases with few prior treatment options (eg, rare diseases or advanced cancers). Although the definition of specialty drug varies by payer, these medications share certain key characteristics.

 Typically, they are complex molecules and may be derived from biologic sources; require highly involved manufacturing processes; require special distribution and handling, such as refrigeration; involve intensive patient education and/or follow-up monitoring to ensure appropriate use; and are high cost. Many specialty medications require injection or infusion in clinical settings and are usually covered under the medical benefit. The remainder are administered at home by self-injection, or oral or inhaled administration, and are almost always covered under the pharmacy benefit.

Despite the therapeutic advances offered by many of these agents, specialty drugs have attracted payer attention because they are often accompanied by higher costs than traditional medications. Although the percentage of patients using specialty drugs is quite small—ranging from 1% to 5%

—a recent report estimated specialty drug spending in the United States at $95 billion in 2013, or about 29% of total prescription drug spending.

 Although published estimates vary depending on which agents are included, about two-thirds of specialty drug spending growth in 2013 was accounted for by agents to treat cancers, autoimmune conditions like RA, and MS.

Since about half of specialty drug spending is on self-administered agents covered by pharmacy benefits, these have been the focus of payer efforts to control spending.

 Insurers and pharmacy benefit managers seeking to manage costs have been unable to use the traditional 3-tiered cost-sharing design to encourage utilization of lower-cost drugs, however, given the fact that specialty drugs often have few close, less-expensive substitutes. As a result, utilization management (UM) tools, such as prior authorization and quantity limits, have been applied instead.

 Nevertheless, growing pressure to control spending has led insurers to increasingly place self-administered specialty drugs on new, separate “specialty tiers.” Whereas tiered cost-sharing designs typically have fixed co-payments of increasing amounts for generics, preferred brands, and nonpreferred brands, respectively, newer specialty tiers usually impose a coinsurance requirement which can be as high as 30% to 50% of the cost of the drug. Although specialty tiers were first broadly implemented with Medicare Part D, use of this strategy (and associated high cost sharing) has grown significantly in other markets, including the employer-sponsored insurance market and the new health insurance exchange plans created under the Affordable Care Act.

 Further, many plans—particularly those under Medicare Part D&mdash;place medications meeting a designated cost threshold (eg, $600 a month or more) on the specialty tier, regardless of whether those medications meet other common criteria for the specialty drug designation.

Despite the market trends in increasing patient out-of-pocket (OOP) costs for specialty drugs, the impact of patient cost sharing on specialty drug utilization and outcomes is unclear. Numerous reviews have summarized the relationship between cost sharing and utilization of traditional oral drugs, but none have evaluated the evidence as it relates to specialty pharmaceuticals.

 Such a review is needed for several reasons. First, patients may have strong demand for specialty drugs if they do not have other treatment options or if they perceive alternative, less expensive treatments to be ineffective or undesirable. In this context, they may be willing to pay a much higher cost share compared with traditional pharmaceuticals. On the other hand, the magnitude of OOP costs may exceed patients’ ability to pay, particularly in the context of overall medical expenses and other basic needs. More information is needed to determine the degree to which patient cost sharing is associated with changes in specialty drug utilization, as well as with health outcomes, use of nondrug medical services, and overall healthcare spending.

We sought to address this gap with a systematic review of the published evidence. In light of the highly variable definitions of specialty drugs across insurers, we focused our review on cost-sharing studies of specialty drug classes with indications for 3 key disease areas: RA, MS, and cancer. These represented the top 3 drivers of specialty drug spending in the United States at the time of our review.

 We examined associations between cost sharing and specialty drug utilization for these indications and draw upon our findings, including the gaps in evidence in light of current market trends, to highlight future directions for specialty drug research and policy.

We conducted an OVID search for all Medline-indexed articles published in English between 1995 and 2014. The primary search was based on various combinations of 2 sets of search terms. The first set included cost sharing and related terms: co-pay, coinsurance, benefit design, tiered benefit, specialty tier, and out-of-pocket cost. The second set included terms for specialty medications and our indications of interest: specialty drug, specialty pharmaceutical, biologic, rheumatoid arthritis, multiple sclerosis, cancer, oncology, carcinoma, leukemia, oncolytics, myeloma, and tumor. Additional studies were obtained from reference lists of identified studies. Identified articles were then independently screened and reviewed by 2 members of the research team to determine whether they met our criteria for inclusion (

These inclusion criteria, applied in the following order, were: 1) published as a peer-reviewed original research article (ie, review articles, editorials, and letters were not eligible), 2) examined the effects of cost sharing (co-payments, coinsurance, or OOP costs) for specialty drugs on at least 1 of our chosen outcomes (specialty drug utilization or spending, medical utilization or spending, or health outcomes), and 3) examined drugs or drug classes that were indicated for RA, MS, or cancer and met the aforementioned high cost criterion for specialty drugs, along with at least 1 additional specialty drug criterion (eg, complex molecule or dispensed through specialty pharmacy). Because anti-inflammatory biologics used to treat RA are also approved for other indications (eg, psoriatic arthritis, ankylosing spondylitis), we did not exclude studies that sampled patients based on use of such drugs rather than diagnosis, even though they may have included patents with conditions other than RA. In light of the limited number of studies available, we also did not impose additional restrictions based on study quality. Nineteen articles met our criteria.

We extracted relevant information from each eligible study, including whether they reported cost sharing to have evidence of effects (ie, statistically significant nonzero effect) or no evidence of effects (ie, no statistically significant effect). When price elasticity of demand estimates were reported or could be derived, we captured this information as the expected relative change in the studied outcome if cost sharing were to double (ie, increase by 100%). Given the heterogeneity present in the cost-sharing measures, reported outcomes, study designs, and analytic approaches employed across the identified studies, our summary of the findings and conclusions are largely qualitative in nature.

Detailed characteristics of the 19 studies included in this review are available in the 

). Several studies examined 1 or more of our indications of interest, resulting in 8 studies for RA, 9 studies for MS, and 8 studies for cancer.

 More than half of the studies (n = 10) examined the effect of cost sharing on specialty drugs covered under the pharmacy benefit only, whereas the remainder examined agents covered under either the pharmacy or medical benefit. The specific specialty drugs examined in each study varied, particularly for cancer. All studies were observational, and a majority (n = 13) used cross-sectional study designs to examine specialty drug use among patients in plans with lower cost sharing compared with patients in plans with higher cost sharing for the specialty drug(s) being studied.

Two studies examined data from individuals enrolled in Medicare Part D,

 whereas all other studies used administrative claims data on privately insured patients in commercial plans or employer-sponsored health plans for current or retired employees. No study directly examined the effect of specialty tier—related cost sharing. In fact, databases used in the vast majority (84%) of these studies were from 2009 or earlier, during which time few private insurers were employing the use of specialty tiers and aggressive cost sharing for specialty drugs.

Studies used heterogeneous methods to measure specialty drug cost sharing; some used continuous measures of either co-payments or coinsurance, or an overall plan cost-sharing generosity index, whereas others created categories of cost-sharing groups based on either arbitrary cutoffs, medians, or quartiles for OOP payments observed in the data. A majority of patients were facing relatively low cost sharing, in keeping with the time frame of the data sources. For instance, 7 (64%) of 11 studies with information on mean OOP costs per month had mean co-payments less than $110 per month, and all 7 studies with median OOP information had median co-payments less than $50 per month. The OOP costs were substantially higher in the 2 studies examining Medicare Part D patients, yet these data are difficult to interpret due to a lack of detail. Medicare beneficiaries faced different levels of cost sharing during the calendar year (eg, 25%-33% coinsurance during an initial coverage phase vs 100% cost sharing during the “donut hole” coverage gap), but the studies did not examine changes during or between specific coverage phases. 

A wide variety of specialty drug use outcomes were reported across the studies, including prescription abandonment (n = 3), initiation or any utilization (n = 8), adherence (n = 9), persistence/discontinuation (n = 7), number of claims (n = 1), and drug spending (n = 1). We found no studies examining the impact of specialty drug cost sharing on medical utilization, spending, or health outcomes. The 

 summarizes key study findings by the type of outcome and indication(s) examined.

 In the 3 eligible studies, prescription abandonment was defined as a reversal of an adjudicated claim for a newly prescribed specialty drug (ie, the prescription was submitted and approved by the insurer but not obtained by the patient, so the pharmacy withdrew [reversed] the claim), with no subsequent paid claim within 90 days of the reversed claim.

 Prescription abandonment may be thought of as a subcategory of primary nonadherence, which is when a physician prescribes a medication but the patient does not submit, or does not pick up, the prescription from the pharmacy.

All studies reported a strong association of higher cost sharing with abandonment (vs initiation) of specialty drug prescriptions, for all indications examined. In one study among privately insured patients, approximately 25% abandoned their specialty medication when the OOP cost on the claim was greater than $200 for MS specialty drugs and greater than $500 for anti-inflammatory biologics, compared with less than 5% to 6% abandonment rates when OOP  costs on the claim were less than $100.

 A follow-up study using similar, but more recent, data reported that 50% to 60% of privately insured patients abandoned anti-inflammatory biologics and MS specialty drugs when faced with $2000 or more in monthly OOP costs (ie, due to high deductibles) compared with 5% to 6% abandonment rates among patients facing less than $50 in monthly costs; however, it should be noted that only a small percentage (2%-4%) of patients were subject to such high cost-sharing levels.

 Even for oral cancer agents, approximately one-fourth of privately insured and Medicare patients abandoned their specialty medication when OOP cost on the claim was greater than $500 compared with less than 5% to 6% abandonment rates with less than $100 in OOP costs.

 Notably, the cost-sharing burden in this study was higher for Medicare patients relative to privately insured patients (46% vs 11% facing greater than $500 OOP costs), but subgroup analyses were not conducted.

Initiation was typically defined as the first-time use of a specialty drug within a study period, among patients with a given disease. We grouped studies that examined any utilization (first time or repeated use) during the study period into this category as well. All studies examining initiation in patients with RA and MS reported a negative association with higher cost sharing. The magnitude of the effect varied across studies, with demand elasticities ranging from —0.03 to –0.33. For example, a 100% increase (ie, doubling) in cost sharing for MS drugs was associated with a 3% to 4% reduction in the probability of initiating these agents in 2 studies,

 but was associated with a 33% reduction in initiation in another study.

 Similarly, doubling of cost sharing for RA biologics was reported to reduce initiation by 5%

 A recent study reported that drug benefit generosity was associated with initiation of RA biologics among the subgroup of patients deemed to have mild-to-moderate disease activity, but not among the subgroup defined as having moderate-or-high disease activity with features of poor prognosis,

 suggesting that disease severity may have been influencing initiation decisions.

Initiation of specialty drugs for cancer, on the other hand, was largely reported to be insensitive to cost sharing in the 3 studies examining this outcome.

 One study found that cancer patients were 26% less likely to initiate the drug rituximab if cost sharing was doubled (ie, elasticity estimate of —0.26); yet, the same study did not find significant effects for the other cancer drugs it examined.

Treatment adherence was commonly measured by proportion of days covered (PDC), or the proportion of total days in a period that the patient had a supply of medication available. Some studies used a continuous measure of adherence, whereas others classified patients as being adherent (or nonadherent) based on whether ≥80% of the observation days were covered with a specialty drug supply (or not).

The evidence on the relationship between cost sharing and adherence was mixed across all 3 indications. As shown in the Table and eAppendix, findings varied based on the disease condition/drug class, the measure of adherence, and the level and type of cost sharing.

 One study of cancer drugs, for example, measured adherence as both a dichotomous variable (PDC ≥0.80) and a continuous variable (PDC), and found effects for the former but not the latter.

 A longitudinal study examining the effects of co-payment increases in an integrated HMO setting reported no relationship between cost sharing and adherence to MS, biologic anti-inflammatory, and cancer drugs.

This may have been related to the fact that 84% of the sample faced increases of only $25 to $50. Another study found that higher cost sharing was associated with significantly lower adherence to MS drugs in a subgroup of patients facing coinsurance, but not in a subgroup of patients facing co-payments.

Discontinuation was generally defined as having a continuous gap of time between prescription fills, during which the individual’s specialty drug supply has run out. The number of days used to define a continuous gap varied across studies (30, 45, 60, 90, and 135 days). Persistence was generally characterized as the duration of time between treatment initiation and treatment discontinuation.

Six of the 7 studies reported a statistically significant increase in discontinuation (or decrease in persistence) associated with increased cost sharing for at least 1 of the indications examined. Although the evidence was mixed for MS and cancer drugs, with 2 studies reporting absence of effects, all 3 studies examining biologics indicated for RA showed associations with cost sharing. However, the magnitude of the effects appeared small even among RA biologic users. For example, one study of employer-sponsored plans reported demand elasticity of —0.04 on the probability of continuation of newly initiated RA biologics (doubling the cost sharing was associated with a 3.8% relative reduction in the probability of continuation of the RA biologics, from 0.80 to 0.77), with continuation defined as use in the subsequent year.

Only 1 study examined the association between higher cost sharing and the number of specialty drug claims,

 which is an additional proxy for utilization. Among those patients who initiated therapy, demand elasticity on the number of claims was —0.04 for rituximab (a doubling in cost sharing was associated with approximately a 4% reduction in the number of claims) and –0.11 for other cancer drugs (bevacizumab, trastuzumab, imatinib mesylate, erlotinib).

One study captured spending on specialty drugs via both medical and pharmacy claims and reported varying effects of cost sharing based on the condition examined.

 The demand elasticities ranged from —0.07 to –0.21 (doubling of cost sharing for MS and RA specialty drugs was associated with 7% and 21% reductions in total spending on specialty drugs for those conditions, respectively). However, a similar change in cost sharing was not associated with spending on specialty drugs for cancer. At the same time, the study found that once patients initiated the specialty drugs, cost sharing had no impact on total drug spending among patients with any of the 3 conditions.

Although numerous studies have examined the effects of cost sharing on traditional pharmaceuticals,

 comparatively few have examined this issue for specialty drugs. Nevertheless, the literature on this topic is growing, with over half of the 19 studies included in this review published in the last 5 years. In general, findings from these studies revealed that higher cost sharing is associated with reductions in utilization of specialty drugs indicated for RA, MS, and cancer. Yet, the evidence is not consistent; the magnitude and/or statistical significance of the associations varied by type of specialty drug use outcome and by disease.

Higher cost sharing appears to have a stronger association with noninitiation or abandonment of a prescription at the pharmacy, and a somewhat smaller association—or no association&mdash;with refill behavior (eg, adherence, number of claims) and with specialty drug spending once patients have initiated therapy. Patients who have already chosen to fill specialty drug prescriptions may be less sensitive to costs because they have a more established understanding of the potential benefits of treatment and/or have already committed to treatment.

Overall, associations between cost sharing and specialty drug utilization outcomes were not as strong as those found for traditional pharmaceuticals.

 Based on the few studies in our review where price elasticity of demand estimates were available, price sensitivity for specialty drugs was lower than the —0.20 to –0.60 range reported in a 2007 review of cost sharing for traditional pharmaceuticals.

By comparison, the studies we reviewed reported elasticities of —0.03 to –0.33 for initiation, –0.04 for discontinuation, –0.04 to –0.11 for number of claims, and –0.07 to –0.21 for drug spending. On the one hand, higher prices for specialty drugs, combined with higher patient cost-sharing levels, may substantially reduce utilization for these medications. On the other hand, the lack of availability of close substitutes at lower OOP costs and the fact that these drugs are often used to treat complex chronic and life-threatening conditions means that patients have few alternatives; therefore, they may decide to pay the cost-sharing amount regardless of its magnitude.

In our review, cost sharing was more likely to show mixed or no associations with many specialty drug utilization outcomes for a life-threatening condition like cancer, as opposed to the relatively more consistent associations for RA. Costs may play a different role in patients’ treatment decisions when a medication is perceived to be a life-saving option. Nevertheless, no matter how high the demand, some patients may be unable to pay in the context of competing obligations and others may purchase medications but subsequently have problems paying for other necessities, face depletion of their financial savings, or even face bankruptcy.

 Such information is not captured in administrative claims, the data source typically used for examining the effects of cost sharing. 

As with any review, our conclusions should be interpreted in the context of our methodological choices. We opted to focus on only 3 disease areas—RA, MS, and cancer&mdash;because of their relevance to specialty drug spending and also because they have been the focus of most available studies. A handful of singleton studies have examined specialty drugs indicated for serious infections, HIV, osteoporosis, kidney disease, and transplants, but it is difficult to draw conclusions about such conditions from such a limited research base.

Limitations of the Evidence Base and Future Directions

In addition to summarizing the evidence, our review identified a number of important limitations in the existing literature that have implications for future research and policy:

Cross-sectional versus longitudinal study designs.

 The majority of available studies were cross-sectional, meaning they could not account for unmeasured differences between patients across plans. Thus, differences in characteristics that may be correlated with specialty drug use may have biased estimates of the effects of cost sharing. Although randomized designs are rarely feasible, there is a critical need for more quasi-experimental research studies using longitudinal data to evaluate outcomes before and after a specialty drug cost-sharing change, relative to a contemporaneous control group.   

UM policies and other specialty drug management approaches. 

None of the cost-sharing studies in our review considered the confounding, interactive, and/or individual effect of UM policies on specialty drug use. Specialty drugs covered under the pharmacy benefit are increasingly subject to more stringent UM tools, such as prior authorization, quantity limits, and, more recently, step therapy.

 If plans that required lower cost sharing were more likely to use UM tools as a substitute to help manage specialty drug costs, then the results from cross-sectional studies would underestimate the true effect of specialty drug cost sharing. Alternatively, if the plans that require higher cost sharing also use UM tools to further control costs, then the results from cross-sectional studies would potentially overestimate the true effect of cost sharing. Similar issues are pervasive if cost-sharing studies do not account for the presence or absence of other specialty drug management approaches, such as clinical care management, use of specialty pharmacies, and clinical pathway programs.

 Understanding the individual and interactive effect of all these approaches on specialty drug use and outcomes is crucial for payers who are using them, or considering them, as a substitute or complement to higher cost sharing.  

Specialty tier level or extremely high cost sharing. 

All but 2 studies in our review focused exclusively on private or employer-sponsored insurance data from 2009 or earlier, when lower cost sharing was more typical

; no studies examined the impact of a specialty tier benefit design.

 As a result, the generalizability of findings is limited. Over 90% of Medicare Part D plans now have a specialty tier wherein cost sharing ranges from 25% to 33%.

 Similarly, a recent analysis of exchange formularies found that approximately 60% of the Silver- and Bronze-level health insurance exchange plans offered in 19 states also contain specialty tiers with coinsurance.

 By 2013, almost one-fourth of workers with employer-sponsored coverage also faced a specialty tier.

 This highlights the need for future research to examine the effects of the higher cost-sharing levels common in today’s marketplace. In the meantime, it may be appropriate to establish policies that provide additional protection for patients against extremely high cost sharing for specialty drugs. This is of particular concern under Medicare Part D, where beneficiaries who do not qualify for low-income subsidies will need to spend up to $4850 out of pocket in 2016 before catastrophic coverage kicks in.

 Similarly, the widespread use of high deductibles coupled with high OOP maximums under exchange plans also raises concern for the health and/or financial well-being of patients with serious chronic conditions.

REVIEW ARTICLE

The authors review published evidence regarding associations between high cost sharing for specialty pharmaceuticals indicated for rheumatoid arthritis, multiple sclerosis, and cancer, and their utilization.

Impact of Cost Sharing on Specialty Drug Utilization and Outcomes: A Review of the Evidence and Future Directions

Appropriate vaccinations are important for patients with rheumatoid arthritis (RA), who are often treated with highly immunosuppressive therapies that increase their risk of infection. However, rates of vaccination among patients with RA are below optimal levels.

We conducted a patient survey to assess self-reported vaccination status and to compare that status with electronic health record (EHR) data.

We recruited randomly selected patients with RA in an academic practice in 2013. Eligible participants had a diagnosis of RA, at least 1 visit to a rheumatology clinic in each of the previous 2 years, were 18 years or older, and had English listed as their preferred language. The survey included the following domains: a) patient self-reported receipt of influenza, pneumococcal (PNVX), and herpes zoster (HZVX) vaccinations; b) attitudes about these vaccines, including reasons for unvaccinated status, if applicable; and c) provider recommendations about these vaccines.

Based on participants’ self-report, we found a high vaccination rate for influenza during the previous season (79.4%), a moderate rate of any previous vaccination for pneumococcus (53.9%), and a very low rate of any previous vaccination for herpes zoster (7.8%). If we assume that all self-reports are accurate and we include vaccinations recorded in the EHR that were not reported by patients, the vaccination rates were approximately 8% to 9% higher for PNVX and HZVX.

Vaccination rates are low among patients with RA based on self-report data. Further research is needed to investigate system-level barriers to vaccination and the impact of evidence-based, provider-level interventions on vaccination rates. 

	Vaccination rates are low among patients with rheumatoid arthritis based on self-report data. 

		Lack of physician recommendation, as recalled by the patient, appears to be the most important factor for unvaccinated status. Only three-fourths of patients said their doctors had discussed their increased risk of infection, and only two-thirds said their doctors discussed the importance of vaccinations. 

		Patient lack of knowledge or negative attitudes toward vaccinations appear to be less important contributors to suboptimal vaccination rates. 

		Further research is needed to investigate system-level barriers to vaccination and the impact of evidence-based provider-level interventions on vaccination rates.

Patients with autoimmune rheumatic diseases have a risk of infection approximately double that of age- and gender-matched controls.

 Patients with rheumatoid arthritis (RA) are at an increased risk for infection due both to inherent dysregulation of the immune system and, for many, the added effect of chronic immunosuppressive therapy. For example, the adjusted hazard ratio for contracting herpes zoster in patients with RA is 1.9 compared with healthy controls.

Because of their increased risk of infection, the Advisory Committee on Immunization Practices (ACIP) recommends that immunocompromised adults receive an annual influenza vaccination (INFVX), as well as the pneumococcal vaccination (PNVX) with the 13-strain pneumococcal conjugated vaccine (PCV-13) followed by the 23-strain pneumococcal polysaccharide vaccine (PPSV-23).

 The recommendations are more complex for herpes zoster vaccination (HZVX), which uses a live virus and has historically been considered contraindicated in patients who are severely immunosuppressed. Currently, ACIP recommends HZVX for all individuals 60 years or older.

 However, a recent study found that HZVX had even higher efficacy (ie, 70% risk reduction) among healthy adults aged 50 to 59 years

; HZVX (Zostavax) has FDA approval for use in adults 50 years or older.

 ACIP states that HZVX is safe for patients who are taking less than 20 mg/day of prednisone and/or low doses of methotrexate (≤0.4 mg/kg/week), azathioprine (≤3.0 mg/kg/day) or 6-mercaptopurine (≤1.5 mg/kg/day).

 If a physician plans to initiate a strong immunosuppressant, ACIP recommends the patient be given the HZVX at least 14 days prior to starting the medication.

 This recommendation has been challenged by findings from a recent analysis of Medicare patients with immune-mediated disease who were given HZVX. There was no increase in herpes zoster infections during the 42 days after HZVX, even among patients receiving biologic immunosuppression, whereas those vaccinated had a lower incidence of zoster over a median 2-year follow-up.

Vaccination rates remain low among RA patients, despite their high risk of infection, strong evidence of vaccine safety and efficacy, and recommendations from national organizations. A recent large study found that only 25% of RA patients were adherent to current vaccine recommendations.

 Studies have shown adherence rates among RA patients ranging from 10% to 34% for INFVX,

 The reasons for these low vaccination rates are not entirely clear.

At our institution, the Northwestern Memorial Medical Center in Chicago, vaccination rates for patients with RA measured using electronic health record (EHR) data have been similar to national data. However, EHR vaccination data may be incomplete because many patients receive vaccinations outside of their rheumatologist’s office and their primary care clinician may practice in a different health system. The completeness of EHR data on vaccinations is also limited, as many patients may get vaccinated in pharmacies and retail stores with no automated way to transfer documentation to their healthcare team.

 Therefore, at the start of a quality improvement research project to improve vaccination rates, we conducted a telephone survey to capture patients’ self-report of vaccination status and to better understand vaccination behavior and attitudes of patients with RA.

This study was conducted at an academic rheumatology clinic from July through September 2013 and was approved by the Northwestern University Institutional Review Board. Structured query language was used to identify all eligible patients from EHR data. Patients were eligible if they had a diagnosis of RA (

International Classification of Diseases, Ninth Revision, Clinical Modification

 codes 714.0-714.9) in the problem list, at least 1 visit to the study clinic in each of the previous 2 years, English listed as their preferred language, and were aged at least 18 years. A total of 1119 patients were identified as eligible based on EHR data. Query output included patient contact information for recruitment. A random number was generated for each patient on the list, and the list was sorted by this number to ensure that a random sample of patients would be recruited.

Our goal was to complete 100 interviews. Assuming a 50% participation rate based on previous work with a similar patient population, we initially selected the first 200 patients for recruitment. Manual chart reviews were done prior to recruitment to confirm that the patients had a diagnosis of RA. After initial chart reviews found that some patients did not have a confirmed diagnosis of RA, we selected an additional 50 patients for possible recruitment. We stopped chart reviews and recruitment of new subjects once we reached 100 completed interviews. Of the 245 manual charts we reviewed, 48 did not have an RA diagnosis, resulting in 197 patients whom we attempted to recruit.

A study interviewer called potential respondents up to 6 times and invited them to participate in a 10-minute structured telephone interview. We varied the time of day for the calls to maximize the chance of contact and to decrease selection bias. A message was left on identified voicemails on the second and fifth attempts asking patients to return the call if they were interested in participating in the study. Patients were offered a $10 gift card for completing the survey.

The survey included published items from the Behavioral Risk Factor Surveillance System survey

 and items developed for this project by the study team. The survey had 22 to 27 items (depending on skip patterns) and addressed the following content areas: a) self-reported receipt of INFVX, PNVX, and HZVX; b) attitudes about these vaccines, including reasons for being unvaccinated, if applicable; and c) provider recommendations about these vaccines. Additionally, if participants reported receipt of a vaccination, we asked for details on the type of setting/place they had received each vaccine. If a participant reported ever receiving an influenza vaccination, we asked if they had been vaccinated during the previous year’s flu season (2012-2013). As HZVX is contraindicated for some immunosuppressed patients, we included an item inquiring whether a provider had ever recommended against receipt of this vaccine. Participants responded to several items regarding attitudes toward vaccinations on a 4-point Likert scale. Open-ended questions were asked to elicit participants’ reasons for not being vaccinated. Interviewers coded responses to open-ended items about reasons for not being vaccinated into the following predefined categories if appropriate: a) no one ever recommended vaccine, b) did not think they needed vaccine, and c) do not like vaccinations/do not think safe. Responses that could not be coded into the above categories were reviewed by 2 authors (DB and DS) and an additional category—d) MD/pharmacist recommended against vaccination&mdash;was added. If more than 1 reason was mentioned, multiple responses were recorded. Demographic items were asked at the conclusion of the survey.

We reviewed EHRs of consented participants who completed the telephone interview to identify whether they were receiving an immunosuppressive drug for treatment of RA, the presence of comorbid conditions, and documented immunizations (administered in the clinic and/or historical vaccinations). We classified patients as receiving immunosuppressive medications if the current medication list included any biologic agents, corticosteroids, methotrexate, leflunomide, or azathioprine; hydroxychloroquine and sulfasalazine were not considered immunosuppressive agents. Comorbid conditions were identified from the participants’ problem list and included cancer, chronic pulmonary disease, coronary artery disease, chronic heart failure, peripheral vascular disease, severe chronic liver disease, diabetes with end organ damage, renal failure, and dementia.

The survey response rate was calculated using guidelines from the American Association for Public Opinion Research.

 Survey responses were summarized using descriptive statistics. We calculated kappa statistics to analyze the agreement between self-reported vaccination and vaccination documentation in EHR data; for these analyses, if a respondent said he or she did not know whether they had been vaccinated, this was categorized as a “no” response.

Of the 197 patients we attempted to recruit, 13 had no valid telephone number, 19 refused participation, 63 were not reached after 6 attempts, and 102 patients enrolled in the study and completed the interview (55.4% response rate). Most participants were female (85.3%) and the mean age was 57.8 years (

). A total of 91.2% of participants were prescribed immunosuppressive therapy based on chart review; 85.2% of participants reported they were taking immunosuppressive therapy.

Most participants (90.2%) reported that they had received INFVX at least once; 79.4% reported receiving INFVX during the 2012-2013 season (

). Of the 81 participants who self-reported INFVX in the last year, only 28 (34.6%) had INFVX recorded in the EHR. This low rate of INFVX documentation in the EHR is consistent with the variety of settings in which patients reported receiving INFVX (

). Of the 21 patients who said they had not received INFVX in the previous year (or were unsure), only 1 (5%) had an INFVX documented in the EHR.

Approximately half of participants (53.9%) reported that they had received PNVX at least once. Only 32 of the 55 (58.2%) who reported getting PNVX had a PNVX documented in the EHR; conversely, of the 47 who said they had never received PNVX, 9 (19.1%) had a PNVX documented in the EHR. If either self-reported or EHR-documented PNVX were included, the rate of receiving 1 or more PNVX was 62.7%.

Only 8 patients (7.8%) reported receiving HZVX; of these, only 1 (12.5%) was documented in the EHR. Of the 94 who said they had not received HZVX, 8 (8.5%) had a documented HZVX in the EHR. Among patients who reported HZVX, 87.5% said they received it at a doctor’s office.

When participants were asked, “How important do you think it is to get vaccinations to prevent infections?” 16.3% said it was somewhat important and 65.3% said it was very important to get vaccinations. However, 15.3% thought vaccines were not important at all. Of note, of the 18 participants who did not feel it was important to be vaccinated, all but 1 were taking immunosuppressive medications at the time of the survey, including 9 taking tumor necrosis factor inhibitors and 12 taking methotrexate. When participants were asked how much they worried about getting infections because of the medications they take for RA, 20% responded “somewhat” and 21% responded “a great deal.”

Participants’ reasons for not being vaccinated varied by type of vaccine. The majority of participants who had not received PNVX or HZVX reported that it had never been recommended to them (

). Patient dislike or distrust of vaccination was more common for INVFX than for PNVX or HZVX. Of the 10 patients who had never been vaccinated for influenza, 7 stated that this was because they did not like or trust the vaccine.

Patient Perceptions of Provider Communication Regarding Vaccines

Three-fourths of respondents said that a physician had told them they had an increased risk of infection (

); however, only 64% recalled being told the importance of vaccines by their providers. Communication about vaccinations also varied by vaccination type (Table 5). Nearly all (96.1%) participants reported that their provider had recommended INFVX, and only 2 patients reported that one of their providers had recommended against INFVX. Only 60.8% said they were told to get PNVX, and only 16.7% reported that HZVX had been recommended (Table 5). Thirteen participants (12.8%) reported they were told not to get HZVX; of these, only 1 patient was eligible for this vaccine (ie, not on biologic therapy).

Based on participants’ self-report, we found a high vaccination rate for influenza during the previous season (79.4%), a moderate rate of any previous vaccination for pneumococcus (53.9%), and a very low rate of any previous vaccination for herpes zoster (7.8%). If we assume that all self-reports are accurate and we include vaccinations recorded in the EHR that were not reported by patients, the vaccination rates were approximately 8% to 9% higher for PNVX and HZVX (Table 2).

A variety of factors likely contribute to suboptimal vaccination rates for patients with RA; lack of physician recommendation, as recalled by the patient, appears to be the most important. Only three-fourths of patients said their doctors had discussed their increased risk of infection, and only two-thirds said their doctors discussed the importance of vaccinations (Table 5). Although almost all participants reported they had been told to be vaccinated for INFVX, less than two-thirds had been advised to get PNVX and only 1 in 6 had been advised to have HZVX. These rates of recommendations correspond well to the self-reported vaccination rates; when patients who said they had not received a PNVX or HZVX were asked why, the most common response was that it was not recommended by their provider.

The reasons why physicians fail to recommend vaccinations for immunocompromised patients are not fully understood. Some failures may occur because patients with RA are often cared for by both a rheumatologist and a primary care physician. The rheumatologist may see preventive care as the responsibility of the primary care physician, but primary care physicians may not be knowledgeable about guidelines for vaccination of immunosuppressed patients or may feel this is the responsibility of the rheumatologist prescribing the immunosuppressants.

A 2009 German study found that only 65% of patients with RA were vaccinated against influenza despite 95% patient awareness of the vaccine’s availability. This was thought to be due to the fact that in Germany, the rheumatologist “delegates” vaccinations to the general practitioner.

Similarly, a 2009 study in Ireland found that approximately half of rheumatologists did not advise influenza vaccination due to insufficient time during the visit, and they also felt vaccination was the responsibility of the general practitioner.

 However, it is not certain whether these European findings are generalizable to the United States. General practitioners in European countries tend to have a more primary role in patients’ care and serve as gatekeepers to specialty services.

 In contrast, in the United States, rheumatologists often share the responsibility of primary care for their patients’ overall health (eg, monitoring cardiovascular risk, blood glucose, malignancy screening), recognizing that many comorbid conditions have a higher prevalence with autoimmune disease. It may be appropriate for specialty societies to address shared responsibility for vaccination and to issue guidance statements to help avoid situations in which responsibility is not clear.

Another factor contributing to lack of recommendation for vaccination is the lack of adequate reminder systems. Patients with RA have complex healthcare needs, and preventive care may be a low priority for providers when they address acute management issues during busy clinic visits. Similarly, physicians have insufficient time to address preventive needs.

 Reminder systems, especially those in EHRs with linked order sets to facilitate prescribing, can help overcome these barriers. Point-of-care paper reminder forms for rheumatologists improved PNVX rates from 67.6% to 80% in patients receiving immunosuppressive medications.

 An EHR alert significantly increased use of both INFVX and PNVX, as well as documentation rates in rheumatology patients taking immunosuppressants.

 Efficacy was better if the process was nurse-driven, which speaks to the potential for team-based care to improve vaccinations.

 The value of such team-based intervention led Kaiser Permanente Southern California to adopt a “Complete Care” program beginning in 2005, which incorporated proactive team-based care, supplemental tactics, and health information technology in order to increase quality of care for patients with chronic illnesses.

CLINICAL

Patients with rheumatoid arthritis self-report a moderate rate of any previous pneumococcal vaccination (54%) and a very low rate of herpes zoster vaccination (8%).

Understanding Vaccination Rates and Attitudes Among Patients With Rheumatoid Arthritis

The burden of visiting pharmacies to fill medications is a central contributor to nonadherence to maintenance medications. Recently, pharmacies have begun offering services that align prescription fill dates to allow patients to pick up all medications on a single visit. We evaluated the prevalence and structure of synchronization programs and evidence of their impact on adherence and clinical outcomes.

Mixed-methods approach consisting of semi-structured interviews, data from surveillance activities, and a systematic literature review. 

We conducted interviews with opinion leaders from nonprofit advocacy organizations and exemplary synchronization programs. Program prevalence was determined using data from regular surveillance efforts. A literature review included Medline, EMBASE, Google Scholar, and general Internet searches. 

Synchronization programs exist in approximately 10% of independent, 6% of stand-alone chain, and 11% of retail store pharmacies. The majority of programs include a monthly pharmacist appointment and reminder communication. Programs reported the importance of pharmacist buy-in, technology to track and recruit patients, links to other healthcare services, and flexible solutions for managing costs and communication preferences. Although existing peer-reviewed literature suggests that synchronization improves adherence, more evidence is needed to evaluate its impact on patient-centered outcomes.

As medication synchronization programs shift directions and compete for patients and payer resources, it will be more important than ever to rigorously evaluate their ability to improve clinical outcomes while also providing the growing number of patients managing multiple chronic conditions with the highest level of patient engagement and consumer choice. 

	Medication synchronization is a novel delivery redesign in pharmacy care that has attracted growing enthusiasm; however, little is known about its impact on adherence and clinical outcomes. 

		An estimated 8% of US pharmacies offer a medication synchronization program—a rate that nearly doubled from 2013 to 2014. 

		Synchronization programs are based on 2 core models with additional features, including technology to track and recruit patients, links to other healthcare services, and flexible solutions for patients to manage medication costs and communication preferences. 

		As programs expand, more attention will need to be devoted to care continuity and cost.

In the United States, chronic noncommunicable diseases are responsible for more than half a million deaths annually and more than $538 billion in direct medical costs.

 Although medications are central to the effective management of these diseases, gaps in pharmaceutical care have been widely documented,

 and are a major contributor to potentially avoidable morbidity, mortality, and health spending. Many factors undermine the ability of patients to adhere to their prescribed therapies,

 and the burden of visiting pharmacies to fill and refill medications has recently been recognized as a central concern.

Patients with chronic conditions must often manage medications prescribed by numerous physicians and may fill their prescriptions on many different days. For example, patients with cardiovascular disease make an average of 20 pharmacy visits annually, and the top decile make more than 43 visits.

 This makes establishing a routine around medication filling challenging, especially when insurance restrictions frequently prohibit refilling until the supply from the prior prescription has been nearly exhausted. The resultant impact on adherence for patients whose prescriptions’ fill dates are not aligned appears to be very large.

To overcome this problem, pharmacies have begun to offer “medication synchronization” services that aim to simplify the refilling process by allowing patients to pick up all of their medications on a single visit. To accomplish this, patients receive partial supplies of their medications in order to align their subsequent refill dates. Medication synchronization programs—which in addition to prescription synchronization often include other pharmacy-based services, such as medication management counseling or vaccination&mdash;have attracted substantial and growing enthusiasm.

 Initial estimates of their impact suggest that, depending on drug class, medication synchronization programs may improve adherence up to 6-fold.

 However, to date, little is known about these programs, how they have been implemented, who they serve, and what features appear to be associated with their success.

We used a mixed-methods approach to determine how common synchronization programs were in 2013 and 2014, how many patients they impacted, how they are structured, and what aspects of their implementation and design appear to be associated with greater success.

To determine the prevalence, scope, and characteristics of existing programs, we conducted interviews with opinion leaders from the National Community Pharmacist Association (NCPA) and Pharmacy Quality Alliance, organizations that have been actively involved in monitoring, developing, and promoting medication synchronization programs. Three investigators conducted in-depth 60-minute telephone interviews, between January and March 2014. Interviewers used a written guide that contained a list of key thematic areas and kept written notes, which were reconciled after every interview. The interviews were semi-structured, with questions designed to elicit insight into the origins of synchronization programs, their current state, and future challenges. This study was approved by the Institutional Review Board at Brigham and Women’s Hospital.

The prevalence of synchronization programs in chain and retail store pharmacies was determined through data collected from our opinion leaders who systematically survey program administrators biannually by e-mail or telephone. Programs report the number of stores with a synchronization program, the number of patients enrolled, and the projected estimates of patient enrollment, which enables leaders to reconcile new data with past projections. This surveillance approach captures information from an estimated 80% to 90% of chain (stand-alone pharmacies with 4 or more stores) and retail store pharmacies (pharmacies embedded in retail outlets, such as supermarkets) nationwide. Program prevalence in independent pharmacies (stand-alone pharmacies with fewer than 4 stores) was ascertained using official and self-reported data collected by NCPA through quarterly surveys to all affiliated pharmacies.

This study evaluates the prevalence, structure, and key features of pharmacy-based programs to synchronize prescription fill dates, about which, little is known.

March 2016

Remembering the Strength of Weak Ties

Impact of Cost Sharing on Specialty Drug Utilization and Outcomes: A Review of the Evidence and Future Directions

Understanding Vaccination Rates and Attitudes Among Patients With Rheumatoid Arthritis

Prevalence, Effectiveness, and Characteristics of Pharmacy-Based Medication Synchronization Programs

Trends in Hospital Ownership of Physician Practices and the Effect on Processes to Improve Quality

LDL Cholesterol Response and Statin Adherence Among High-Risk Patients Initiating Treatment

National Estimates of Price Variation by Site of Care

The Budget Impact of Cervical Cancer Screening Using HPV Primary Screening

Value of Primary Care Diabetes Management: Long-Term Cost Impacts

Organizational Structure for Chronic Heart Failure and Chronic Obstructive Pulmonary Disease