Since the discovery of the hepatitis C virus (HCV) in 1989, the chronically infected population has experienced dynamic change. The prevalence of chronic HCV infection in the United States has decreased over the past decades, with the most recent estimate at approximately 2.7 million people (or 1%) of those 6 years and older.

 The decline corresponds with the increase in HCV-associated deaths and decreased transmission rather than from an increase in treatment success.

Increasing access to more effective and affordable treatments is a major public health concern.

Chronic HCV infection remains largely undertreated, with only 13% to 18% of infected individuals having received treatment.

 The largest barrier to treatment is that many infections remain undiagnosed, with fewer than half of all HCV-infected individuals being aware of their infection.

 Other barriers to treatment include contraindications or perceived contraindications by prescribers, lack of access to prescribers with HCV expertise, and patient barriers (eg, the asymptomatic nature of the infection, fear of medication side effects, and concerns regarding treatment duration, cost, and effectiveness)

 Patients and prescribers have postponed treatment in hopes of more effective and more tolerable treatments on the horizon.

After developing chronic HCV infection, 60% to 70% will progress to chronic liver disease; 5% to 20% will develop cirrhosis; and 1% to 5% will die from cirrhosis or liver cancer.

 However, these sequelae take decades to develop, and for most patients, there is no urgency for treatment. Treatment is recommended for individuals with existing liver disease or fi brosis, but may be delayed for those with less severe disease.

As the majority of patients are believed to have acquired their infection between the 1960s and the 1980s, the proportion of newly diagnosed patients with mature infection requiring immediate treatment is steadily on the rise.

 Chronic infection is more often found among individuals over age 50 years. Approximately 81% of individuals with HCV infection were born between 1945 and 1965.

 In 2012, the Centers for Disease Control and Prevention issued guidance that all persons born in this time frame should be screened for HCV at least once, regardless of risk factors.

 With increased screening, more individuals are likely to be diagnosed and receive treatment in coming years.

The goal of therapy is to eradicate HCV infection, and with it to prevent liver cirrhosis, liver failure, hepatocellular carcinoma (HCC), and death.

 The eradication of HCV is determined by a highly sensitive assay in which circulating HCV RNA is undetectable at 12 or 24 weeks after completion of treatment—known as sustained virologic response (SVR). SVR at 24 weeks has been shown to provide a durable response and is associated with improvement in liver fibrosis, reduced risk of liver-related morbidity and mortality (including liver failure, liver transplantation, and HCC), and reduced risk of all-cause mortality, even in advanced cases.

 In 2013, undetectable serum HCV RNA at 12 weeks after the end of treatment was found to be concordant with testing after 24 weeks, and has become the new standard of care and end point used in clinical trials.

Genotype 1 is the most common HCV genotype in the United States, comprising approximately 70% of all cases. It is also the most difficult to treat, requiring prolonged therapy. Beginning in 2001, pegylated interferon plus ribavirin was the standard-of-care treatment for all genotypes. A 48-week regimen with pegylated interferon and ribavirin for genotypes 1, 4, 5, and 6 typically resulted in SVR rates of 40% to 50% (

). In clinical trials, treatment-naïve patients with HCV genotypes 2 and 3 treated with pegylated interferon plus ribavirin for 24 weeks often obtained SVR rates of 70% to 80%.

The SVR rates achieved in clinical trials may not always be realized due to suboptimal patient adherence in the general population.

 Severe side effects often negatively impact patient adherence to therapy.

Pegylated interferon products have a black box warning of fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. The side effects of pegylated interferon that often cause the most frequent complaints from patients are the flu-like symptoms, which must be tolerated for up to 48 weeks. Ribavirin also has serious side effects, including anemia, which can worsen heart disease, and teratogenicity.

In 2011, 2 direct-acting antiviral (DAA) non-structural (NS) 3/4A protease inhibitors, boceprevir and telaprevir, were approved to treat genotype-1 HCV. SVR was achieved for an additional 25% to 31% of treatment-naïve patients treated with boceprevir or telaprevir plus pegylated interferon and ribavirin compared with standard dual therapy.

 Boceprevir and telaprevir require complex treatment response—guided regimens, carry signifi - cant pill burdens, and have greater incidence of severe side effects such as cytopenias and skin reactions.

 Boceprevir and telaprevir are both substrates and inhibitors of P-glycoprotein and cytochrome P450 3A4, which can cause significant drug interactions. In one cohort study, potential drug interactions that required dose adjustments or medication changes were found in half the population initiating boceprevir or telaprevir.

In late 2013, 2 additional oral DAAs were approved. Simeprevir, a third NS3/4A protease inhibitor, was approved for use in conjunction with pegylated interferon and ribavirin to treat HCV genotype 1. Advantages of simeprevir over first-generation NS3/4A protease inhibitors include once-daily dosing, slightly improved SVR rates, and an improved side effect profile. Overall, 80% of patients achieved SVR; however, among patients with genotype 1a, 58% of patients achieved SVR with the NS3 Q80K polymorphism compared with 84% of patients without the polymorphism.

 It is recommended, but not required, that patients be screened for the NS3 Q80K polymorphism prior to initiating regimens including simeprevir.

The most recent DAA addition is sofosbuvir, the first NS5B polymerase inhibitor approved to treat chronic HCV and the first approved medication for use in an all-oral HCV treatment regimen. Sofosbuvir provides the additional advantages of once-daily dosing, improved SVR rates, efficacy for all genotypes, no cytochrome P450 3A4 drug interactions, and shorter therapy duration (12 weeks total) for certain patients. Among genotype-1 treatmentnaïve patients, SVR was achieved for 89% with sofosbuvir, pegylated interferon and ribavirin for 12 weeks.

 Limited results are available for sofosbuvir use in patients with genotype 1 who had failed prior therapy with pegylated interferon, and ribavirin; however, the US Food and Drug Administration (FDA) allowed approval of sofosbuvir in this population based on extrapolated results from other difficult-to-treat patient populations. The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) have released treatment guidelines that recommend sofosbuvir regimens, including the unapproved sofosbuvir and simeprevir combination regimen, as standard-of-care treatments (

Chronic HCV infection has been costly to treat, with average wholesale prices (AWPs) of pegylated interferon products ranging from $20,309 to $44,424 per treatment as of February 2014. The treatment of genotype-1 HCV significantly increased with the addition of NS3/4A protease inhibitors. Current AWPs for NS3/4A protease inhibitors range from $43,808 to $79,632 per treatment. Sofosbuvir has been launched with AWP of $1200 per day. Based on AWP pricing, 12 to 24 weeks of sofosbuvir costs $100,800 to $201,600. The high cost of treatment has raised concerns among patient advocacy groups and payers.

 As the treatment costs vary widely across the new standardof- care regimens, this analysis quantifies the proportion of patients initiating sofosbuvir and simeprevir, including interferon-free regimens. An understanding of prescribing patterns with these new drugs will help payers manage appropriate utilization and project drug spend.

A retrospective, cross-sectional analysis was performed using de-identified data from a sample of participating clients in the research database of MedImpact Healthcare Systems, Inc, a national pharmacy benefi ts manager (PBM). Patients initiating sofosbuvir or simeprevir from November 22, 2013 (the FDA approval date for simeprevir; the FDA approval date for sofosbuvir was December 6, 2013), through February 28, 2014, were identified. The first fill date for sofosbuvir was considered the index date. If no fill for sofosbuvir was identified, the first fill date of simeprevir was defi ned as the index date. Each identifi ed patient’s HCV treatment regimen was determined by looking for fill dates of other HCVindicated medications during the concomitant therapy period, which extended from 30 days prior to the index date through 30 days after the index date. The number of patients taking each of the following FDA-approved or ASLD/IDSA-recommended regimens was identifi ed: (1) sofosbuvir, pegylated interferon and ribavirin; (2) sofosbuvir and ribavirin (no interferon products, no protease inhibitors); (3) simeprevir, pegylated interferon, and ribavirin; (4) simeprevir and sofosbuvir with ribavirin (no interferon products); (5) simeprevir and sofosbuvir (no interferon or ribavirin products). Treatment costs were quantified using February 2014 AWP for branded products and maximum acquisition cost (MAC) for generic products (ie, ribavirin products).

In the first few months of market availability of simeprevir and sofosbuvir, nearly 8 times as many patients have initiated sofosbuvir (n = 435) as initiated simeprevir (n = 57) (

). These groups are not mutually exclusive. In fact, 95% of simeprevir initiators are taking unapproved, ASLD/IDSA-recommended, interferon-free, sofosbuvir-based regimens. Only 5% of simeprevir initiators began the FDA-approved regimen with pegylated interferon and ribavirin.

Of sofosbuvir initiators, only 41% are taking concomitant pegylated interferon and ribavirin and more than half (57%) are taking interferon-free regimens indicated for genotypes 2 and 3 and interferon-ineligible genotype 1. Two percent of sofosbuvir users did not have claims for recommended concomitant therapy during the 30 days prior to and 30 days after sofosbuvir initiation.

The AWP cost per treatment for 48 weeks of pegylated interferon and ribavirin (standard of care for genotype-1 patients from 2001-2011) is $42,411 to $46,218 (Figure 4). The HCV protease inhibitor—based regimens (boceprevir, telaprevir, or simeprevir with pegylated interferon and ribavirin) are signifi cantly more expensive at AWP costs of $70,768 to $126,432. The AWP cost of a sofosbuvir- based regimen for genotype-1 treatment-naïve or relapser, interferon-eligible patients is between $122,006 and $123,909. The cost of interferon-free sofosbuvir regimens, recommended for interferon-ineligible genotype-1 patients, ranges from $180,432 (sofosbuvir, simeprevir for 12 weeks) to $202,497 (sofosbuvir, ribavirin for 24 weeks). The latter AWP treatment cost is 66% more expensive than the 12-week interferon-based sofosbuvir regimen and approximately twice as much as the protease inhibitor based–regimens that were standard of care between 2011 and 2013.

Our pharmacy claims—based analysis found that 41.1% (n = 180) of patients initiating sofosbuvir or simeprevir were taking concomitant pegylated interferon and ribavirin. A greater proportion of patients (57.1%, n = 250) initiated an interferon-free sofosbuvir regimen. Most health plans covered by our PBM elected to use prior authorization guidelines to determine appropriate use for medication coverage that is consistent with approved indications and evidence-based standard of care. As the proportion of genotype 1 among the chronic HCV population in the United States is at least 70%, it is expected that a similar proportion of sofosbuvir initiators would be on the FDA-approved regimen for genotype 1 (sofosbuvir, pegylated interferon and ribavirin). It may be that a greater proportion of genotype 2 or 3 patients have initiated therapy in this early time period or that a large proportion of genotype 1 patients initiating therapy have been deemed interferon-ineligible. The cost implications of the latter scenario are significant, as treating genotype 1 patients with an interferon-free regimen costs between $58,426 and $80,491 more per patient, and with decreased efficacy. An SVR of 72% was realized in a total of 211 treatment-naïve genotype 1 patients using sofosbuvir and ribavirin in various clinical trials.

 The AASLD/IDSA guidelines recommend that the all-oral combination of sofosbuvir with ribavirin for 24 weeks should be considered only for genotype-1 patients who require immediate treatment, because regimens with improved safety and efficacy will likely be available by 2015.

The higher costs of more efficacious treatment may be justified as the costs of treatment failure are significant. One analysis found a 10-fold difference in the costs between managing patients who achieved SVR versus those who did not achieve SVR over a 5-year period, with a retreatment rate of 19% among SVR nonachievers.

The outstanding question is whether these new standard-of-care therapies are cost-effective. A Markov model analysis, published months before sofosbuvir was approved, determined that $112,653 was the maximum drug cost for an all-oral regimen achieving 90% SVR to remain cost-effective using a $100,000 per quality adjusted life-year willingness-to-pay threshold.

 For most patients, the current all-oral sofosbuvir-based regimens do not meet the 90% SVR standard of efficacy and are much more expensive.

The standard of care for the treatment of chronic HCV infection continues to evolve. Several novel drugs are being studied in which preliminary data demonstrate close to 100% SVR (Figure 1).

 The future standard of care will be oral regimens that are more effective and presumably more tolerable. Present interferon-free regimens have less evidence of efficacy and a substantial cost (between $180,881 and $202,497 per treatment) for the majority of patients who will receive these treatments. It is yet unknown if the current trend of increasing costs for chronic HCV treatment will continue, or at what point it will no longer be sustainable.

Articles

The American Journal of Pharmacy Benefits

This article is an early utilization review of newer, more effective, and more costly regimens for the treatment of hepatitis C.

Recent Trends in the Treatment of Chronic Hepatitis C

Back in June 2012, I wrote that a healthcare revolution was already under way in this country, and that there was no turning back.

 The Affordable Care Act (ACA) is the law of the land and millions of people are reaping the benefits—no discrimination for preexisting conditions or gender, improved coverage for children and the poor, and changes in Medicare to better serve the elderly caught in the “donut hole,” to name only a few of the monumental advancements to healthcare delivery. As more and more people become aware of the ACA and see the law in action, we face a new opportunity this summer. This is an opportunity to make the law better and strengthen the health insurance marketplace.

The final rule on essential health benefits, actuarial value of qualified health plans (QHPs), and accreditation of issuers laid out the standards that are now in effect for calendar year 2014 and 2015.

 This year, the Obama administration is expected to evaluate the current structure of the insurance marketplace and begin working on standards for 2016, which will be released in early 2015. This document will provide new guidance to QHPs to ensure continued access to affordable health coverage. This year is the advantageous moment to build on the successes already achieved under the ACA and to enhance marketplace operations in a way to make them more patient focused. In particular, the patient advocacy community believes there are needed improvements in 5 core areas: nondiscrimination, transparency, uniformity, continuity of care, and enforcement (

The ACA took a groundbreaking step in healthcare delivery by outlawing QHPs from discriminating against people with preexisting conditions. But the guidelines need to be more specific to prevent any unintended restrictions on care for people with complex chronic conditions.

For example, out-of-pocket costs must not create a barrier to access. Even though there is an out-of-pocket maximum on individual healthcare costs, people with complex—and expensive&mdash;healthcare needs could conceivably face their $6350 limit in the fi rst month of coverage.

Benefit designs should not create discrimination caused by unfair plan design elements, including utilization management techniques, the structure of the formulary, and cost-sharing requirements. QHPs should also provide meaningful access to healthcare providers across various specialties.

Purchasing health insurance can be a daunting task for people, and particularly for individuals who have never had to buy insurance before the ACA and its mandate for coverage were enacted. The only way patients will be able to make intelligent purchasing decisions is if they have access to complete details about the coverage and cost of QHPs offered in their state.

Information about plans should be designed in a way that leads to an understanding of the enrollee’s options. The information should be accessible in a variety of ways so it may serve a diverse patient population, such as via print, Web, and mobile devices. Patients should have easy access to comprehensive details about each plan prior to enrollment. Easy-to-understand, easy-to-locate formularies and provider network lists should be required of all plans.

Hand-in-hand with meeting transparency requirements, QHPs also need to provide their information in a uniform manner to make it easier for patients to compare plans side-by-side. The federal government should develop and require QHPs to use a standard template for formularies and provider networks. There also needs to be a uniform process that is clear and easy to navigate for people who need to file grievances with their plans or appeal adverse plan coverage determinations. These determinations should be easy for patients to understand and include a uniform definition of what services are deemed a “medical necessity.”

As people with chronic conditions become savvier about purchasing health insurance, they will naturally consider changing their plans during an approved enrollment period in order to better meet their budget and health needs. They should have the freedom to transition to new plans, and to do so without encountering repeated barriers.

QHPs should be required to fill prescriptions for patients who are transitioning into the new plan and also stabilized on specific medications. Plans should honor any prior authorization, step therapy, or exceptions process already attained by an enrollee. Plans should also allow the transitioning patient to continue treatment for a set period of time under the care of a prior physician or specialist and receive care as if the provider is “in network.”

With 16 states (and the District of Columbia) running their own insurance marketplaces, 15 others with various forms of federal-state arrangements, and 19 federally facilitated marketplaces, there are bound to be differences.

 For the approximately 36 million people who relocate each year, these differences could be a rude awakening when they shop for a health plan in their new community.

Patients should be confident that any QHP sold through the marketplace meets federally established nondiscrimination standards and that the threshold is uniform across the United States. There should be a federal monitoring program to ensure that appropriate quality checks are in place to guarantee that QHPs are meeting federal requirements and that states are held accountable for plans not in compliance.

The patient advocacy community has created a list of basic principles that it believes should guide the federal government as it considers modifi cations to the insurance marketplace. In the coming months, all stakeholders in the health community—including insurance companies; provider organizations; and pharmaceutical, biotechnology, and medical device companies&mdash;will be invited to work with the National Health Council and its patient advocacy organization members to sketch out potential solutions. We believe that as long as the patient&mdash;especially the patient with complex chronic conditions&mdash;is at the focal point of the discussion, then the solutions will ensure a more robust and effective healthcare marketplace for all.

As the administration looks at improving the insurance marketplace, patient advocates are developing a wish list of modifications to ensure that it is more patient focused.

Making the Marketplace More Patient Focused

As pharmacy benefit costs continue to rise, health insurers and plan sponsors are increasingly implementing utilization management programs across a broad array of drugs and drug classes.

 The Academy of Managed Care Pharmacy defines utilization management as

“…managing the use of medical services to ensure that a patient receives necessary, appropriate, highquality care in a cost-effective manner. As it applies to a pharmacy benefit, utilization management is any of a number of measures used to ensure appropriate medication utilization. Such measures may include quantity limitations, step-therapy, prior authorization, and/or additional steps as deemed appropriate by the health plan’s Pharmacy and Therapeutics (P&T) Committee.”

Utilization management programs have been a mainstay of managed care pharmacy clinical programs for over 20 years, with prior authorization (PA) being the most common.

 A 2013 survey conducted by the Pharmacy Benefit Management Institute reported that 86% of 424 employers use PA as one of their utilization management tools, a 10% increase from the prior year.

 However, PA programs have been criticized for being time consuming and a potential barrier to medication access. Although little research has been done to evaluate these criticisms, there is concern that PA programs may lead to increased healthcare resource consumption and costs.

One reason for prescription abandonment is high out-of-pocket (OOP) member cost shares.

 A linezolid claim could be more than $2000, and often carries high member cost share; as such, studies on linezolid have primarily focused on the economic outcomes following a reversed claim. A reversed claim generally indicates that a prescription was received by a pharmacy but never dispensed to the member. A 2010 retrospective analysis of Medicare Advantage claims evaluated the incidence of linezolid claim reversals in patients recently discharged from the hospital. In the 60-day period following the linezolid reversal, investigators found that 34.9% of patients did not receive any antibiotics and that there were signifi cantly higher medical costs among those with a reversed claim for linezolid. When costs among members with paid (non-reversed) linezolid claims were compared with those with reversed claims, the group with paid linezolid claims had higher drug costs offsetting their lower medical costs, making total cost of care no different between groups.

 Another Medicare study found similar results: higher total medical costs were associated with linezolid claim reversals, and the reversals were more common among members with a high cost share. In addition, members with a reversed linezolid claim also experienced higher rates of rehospitalization.

 These study findings may discourage development of programs aimed at linezolid or antibiotics in general.

Linezolid, a synthetic oxazolidinone antibiotic, was approved by the US Food and Drug Administration (FDA) in 2000 for the treatment of bacterial pneumonia, skin and skin structure infections, and vancomycinresistant enterococcal (VRE) infections.

 While linezolid is considered a broad spectrum Gram-positive antibiotic with low resistance rates, widespread use is not without risk. Reportedly, up to 50% of all antibiotic use is unnecessary and can contribute to antibiotic resistance.

Also, antibiotic prescribing trends differ regionally across the United States, with southern states showing rates of 936 per 1000 persons compared with 639 per 1000 persons in the western states.

In 2007, the FDA issued a safety alert after results from a study evaluating linezolid use in catheter-related infections demonstrated higher mortality in patients treated with linezolid (21.5% vs 16.0%).

 Furthermore, linezolid has been associated with serious central nervous system reactions when administered with commonly prescribed serotonergic medications (eg, SSRI antidepressants).

Antibiotic resistance is a global problem. The gaps in our knowledge about resistance are due to limited capacities to detect and respond to emerging antibiotic resistance threats.

VRE infections are considered a serious threat by the Centers for Disease Control and Prevention.

 Appropriate use of linezolid is paramount, considering the potential for antibacterial resistance and safety concerns. The objective of this study was to evaluate the economic and clinical outcomes of a linezolid appropriate-use PA program in commercially insured members compared with a concurrent comparison group who were not exposed to the program.

The study compared an intervention group with a comparison group using a quasi-experimental concurrent design. The intervention group study population was identified using retrospective administrative pharmacy claims data from a commercial Blue Cross Blue Shield (BCBS) plan in the southern United States. This health plan had an average of 1.4 million members per month and implemented a linezolid PA policy on January 1, 2009. A concurrent comparison group was identified from a different commercially insured BCBS population in the Midwest United States with an average of 1 million members per month that did not implement the linezolid PA program. For both the intervention and comparison groups, members were required to be continuously enrolled for 6 months prior to their index linezolid claim.

The PA policy rejected all linezolid claims at the point of sale. A prescriber was required to contact the health plan and request coverage. The PA policy stated that the intent of the linezolid PA was to ensure appropriate selection of patients for treatment according to product labeling and/or clinical studies and/or guidelines. Appropriate use was defined as treatment of a serious, life-threatening infection or sepsis due to vancomycin-resistant Enterococcus faecium or Enterococcus faecalis, or a documented infection due to Staphylococci that are resistant to beta-lactams, macrolides, clindamycin, and co-trimoxazole (eg, methicillin-resistant Staphylococcus aureus [MRSA]). Oral tablet and oral suspension dosage forms were included in the program, and approval—when granted&mdash;was for 6 months.

During the period of January 1, 2011, through June 30, 2011, each member’s earliest linezolid pharmacy claim that was rejected (for the intervention group) and paid (for the comparison group) was identified and defined as the index claim. All pharmacy claims were identified using the assigned Generic Product Identifi er (GPI, Medi- Span, Indianapolis, Indiana), starting with 1623. Member characteristics from the index claim included age, gender, and zip code—derived median income and education. Charlson Comorbidity Index (CCI) score was calculated in the pre-6–month period.

 The baseline number of outpatient visits, hospitalizations, and emergency department (ED) visits were also collected in the 6 months prior to the index linezolid claim. Members’ infectious organism(s) were collected using

 International Classification of Diseases, Ninth Revision

) codes found in the 6 months prior to the index claim in any field of the member’s medical claims. Infectious organisms were hierarchically ordered and categorized as follows: (1) infections with drug-resistant organisms specific to vancomycin, MRSA pneumonia, MRSA septicemia, or MRSA carrier status; (2) infections due to undefi ned organisms; and (3) all other infectious organisms.

To assess the drug-use patterns following the index claim, all pharmacy and medical claims were queried during the 30 days after the index date for the presence of drug supply for linezolid or any other antibiotic agent. Linezolid medical claims were identified using the Healthcare Common Procedure Coding System (Level II) J2020 code. For evaluating drug supply presence on specific follow-up dates, an end date for each claim (ie, fill date plus days of supply on the claim) was created. On each day evaluated after the index date (ie, day 30 and 60), presence of linezolid and any other antibiotic was reported in the following hierarchical order: (1) linezolid with or without another antibiotic; (2) other antibiotics (without linezolid); and (3) no antibiotic therapy. Hospitalizations and ED visits were identifi ed in the medical claims using revenue codes or place-of-service codes when revenue codes were not available. Outpatient visits were also identifi ed using medical claims Current Procedural Terminology codes (99201 through 99205 and 99211 through 99215). Economic outcomes were evaluated in the follow-up periods using all pharmacy and medical claims and total paid amounts (member share plus health insurer payment). Costs specific to linezolid and all other antibiotics are reported separately. Linezolid and all other antibiotic costs from both the pharmacy and medical benefi t were identifi ed and reported. Total cost included all pharmacy plus all medical costs.

Unadjusted comparisons between groups were performed with the χ² test for categorical variables, Fisher’s exact test for those with counts less than 5, Wilcoxon rank-sum test for counts, and the likelihood ratio test for expenditures. A logistic regression model was used to test hospitalization and ED visit differences between the intervention and comparison groups, with adjustment for: age group, male gender, Charlson Comorbidity Index score categories (0 as the reference, 1-2, and greater than or equal to 3), zip code—derived education dichotomized to those with a bachelor’s degree or above and all others, zip code–derived income dichotomized to $0 to $49,999 and greater than or equal to $50,000, existence of baseline hospitalization or ED visit, and hierarchical presence of specific 

) with Group 2 as the reference. The logistic regression fit was assessed using the C-statistic and Hosmer-Lemeshow goodness-of-fit statistic. Cost analyses were performed using the generalized linear model with Gamma distribution and adjusted for the same covariates listed above. The overall fit of the generalized linear model was assessed using the scaled deviance and Pearson χ² goodness- of-fi t statistic. All statistical testing was performed using SAS version 9.2 (Cary, North Carolina). All 

 values were 2-sided with an a priori alpha of .05. A sensitivity analysis was performed repeating all analyses using a 60- day follow-up period, post index date.

 shows the analysis fl ow for the intervention and comparison health plan members. Of the 1,167,888 eligible members exposed to the PA in the intervention group, 217 (2 per 10,000) had a rejected linezolid index claim between January 1, 2011, and June 30, 2011. The prevalence of members who were continuously enrolled 6 months prior to their index claim was 185 (85.3%) of the 217 members with a linezolid rejected claim. The comparison group had 77 (1 per 10,000) members with a paid linezolid claim, and 69 (89.6%) met analysis criteria. A χ² test was performed to test the difference in rate of linezolid prescribing between the 2 groups, and the intervention group had a significantly higher linezolid prescribing rate compared with the comparison group. (

<.001). This difference refl ects national antibiotic prescribing trends, which show higher rates in the South.

Table 1 shows that all baseline characteristics were similar, except that the intervention group had a significantly lower percentage of members with a zip code—derived median income of >$50,000 (

 = .032). In addition, directional differences existed between the categories of infectious organisms (category 1: infections with drug resistant organisms specific to vancomycin, MRSA pneumonia, septicemia, or carrier status was found in 27.0% vs 39.1% of members; and category 2: infections due to undefined organisms found in 61.1% vs 50.7% of members, among intervention and comparison groups, respectively).

The unadjusted number of offi ce visits, hospitalizations, and ED visits are shown in 

. During the 30-day follow-up, the intervention group had an average of 3.0 office visits (standard deviation [SD] 2.1) and the comparison group 2.0 (SD 1.4), 

 = .332. There were no statistical differences in unadjusted hospitalizations (14.6% vs 17.4%) or ED visits (18.4% vs 14.5%) between the intervention and comparison groups, respectively.

During the 30-day follow-up, a paid claim for linezolid was found in 99 (53.5%) of 185 members initially denied linezolid coverage as a result of the PA (

). The mean time to linezolid claim was 2 days from the index date. The presence of any antibiotic claim, including linezolid, was found in 157 (84.9%) intervention group members, with an average time to first claim of 2 days. There were 28 (15.1%) intervention group members with no antibiotic claims during the 30-day follow-up. This subset of 28 members had baseline characteristics similar to those of the full intervention group (data not shown). There were 4 denials after a member had initiated the PA process. Denials were based on the approval criteria listed in the Methods section. The 4 members had culture information indicating that their respective organisms would be susceptible to other antibiotics, and in all cases, linezolid had not been started when the request came in. Also, a subanalysis comparing unadjusted counts of offi ce visits (2), hospitalizations (4 [14.3%]) and ED visits (5 [17.9%]) showed no statistical differences versus the comparison group during the 30-day follow-up.

The logistic regression model found no difference in hospitalization (

 = .332), or combined hospitalizations/ED visits (

 = .661) between the intervention and comparison groups (

). The generalized linear model showed the intervention group had 37% lower pharmacy costs (relative cost [RC] 0.63, 

 = .016) and 38% lower total cost of care (RC 0.62, 

 = .012) than the comparison group. Mean per member overall total costs of care after adjusting for covariates were $5868 lower in the intervention group, 

). There was no difference in adjusted medical costs (

 = .155) between groups (Table 5). The zip code—derived income difference between the 2 groups was significantly different and is consistent with the income differences between the Midwest and Southern United States that are found in the US Census data. Higher income may influence willingness to forgo insurance coverage and pay out of pocket for linezolid. Therefore, zip code–derived income was included in the multivariate model. Through inclusion of income in the multivariate model, the independent impact of the difference in income between the 2 groups on the study outcomes has been accounted for statistically.

In the 60-day sensitivity analysis, average member linezolid plus all other antibiotic costs remained signifi cantly lower, by $714 for the intervention group ($2083 vs $2847 for the comparison). The number of members with no evidence of any antibiotic claims in the 60-day follow-up dropped to 23 (12.4%), down from 15.1%. Overall, total adjusted costs remained lower in the intervention group; however, not statistically significantly lower. The logistic regression model continued to demonstrate no difference in hospitalizations (

 = .891) or combined hospitalizations/ED visits (

 = .851) between the intervention and comparison groups.

The differences in cost for the intervention group resulted in overall savings from the linezolid PA program. The average total cost per member for linezolid was $1303 higher in the comparison group, 

= .004 (Table 3). During the 30-day follow-up, mean member linezolid plus all other antibiotic costs were $1680 in the intervention group and $2595 in the comparison group, for a per patient $915 difference (

 <.001). Net antibiotic savings from the linezolid PA was $169,275 (185 patients per $915) or $0.024 per member per month (PMPM) ($169,275 divided by [1,167,888 members per 6 months]).

Per year, it takes approximately 15 hours to develop criteria for, 10 hours to implement, and 9 hours to maintain a PA program. Clinical review fees average $20 to $25 per case. Implementation costs for the intervention group were $2250 (15 + 10 hours per $90 per hour). Ongoing operational costs are $0.0005 PMPM [(9 hours per $90 per hour) + (332 cases per year per $20 per case)] / (1,167,888 covered lives / 12 months per year). Given that implementation occurred prior to our analysis, and that the ongoing costs are so low, the net savings would not be affected by administrative costs.

In April 2013, the geographic pattern of US outpatient antibiotic prescribing was highlighted, and researchers noted that up to 50% of antibiotic prescriptions may be unnecessary and contribute to resistance.

 We identified a diagnosis of drug-resistant microorganisms or MRSA in approximately one-third of members attempting to utilize linezolid; continued off-label use could further potentiate resistance. A health plan or PBM can influence appropriate use through implementation of a PA program. In this study, the linezolid PA resulted in no statistically significant differences in hospitalizations or ED visits. The intervention group appreciated a $0.024 PMPM antibiotic savings over a 30-day follow-up period with both clinical and economic findings maintained at 60 days. These results demonstrate that such a program aimed at the antibiotic linezolid could be applied without a concern for an increase in negative clinical consequences.

To our knowledge, few studies have been published examining the impact of a PA on medical outcomes, and none have focused specifi cally on linezolid. Published evaluations of PAs have been primarily focused on proton pump inhibitors, mental health medications (antipsychotics and antidepressants), cyclooxygenase-2 inhibitors, and diabetes medications.

 Additionally, the majority of PA research only reports economic outcomes and even less reports medical costs and utilization. Moreover, study participants are most often from Medicaid or Medicare Advantage populations, making comparisons with other market segments diffi cult, and some of the research lacks a comparison population altogether.

Given the paucity of PA data with which to compare and contrast our results, we chose to compare the impact of the PA program with studies involving members that had a reversed claim for linezolid. Both a linezolid PA claim and a reversed linezolid claim could result in treatment switching and/or delays. In 2010, researchers examined the impact on healthcare utilization by Medicare Advantage patients who were recently discharged from the hospital and who had experienced reversed linezolid claims.

The authors theorized that the high OOP linezolid costs, to which the member may be exposed, could result in treatment delays and hospital readmission. The patients with reversed linezolid claims experienced signifi cantly higher adjusted postdischarge medical expenditures ($10,594 [95% confi dence interval (CI), $8803-$12,705] vs $7953 [95% CI, $7292-$8673]) and lower adjusted postdischarge drug expenditures ($759 [95% CI, $630-$915] vs $2289 [95% CI, $2105-$2488]). The adjusted total costs were not signifi - cantly different. The impact on actual rehospitalizations, or outpatient and ED visits, was not reported. The authors noted that member cost share was the strongest predictor of claim reversal based on a propensity score model. Other research, published in poster form, also demonstrated signifi cantly higher healthcare costs in a Medicare Advantage group that was exposed to a coinsurance, resulting in OOP linezolid costs of more than $100 per claim.

 Members with reversed linezolid claims, presumably due to high OOP costs, experienced higher infection-related and 30-day allcause hospital readmissions than those without a reversal.

Our study results are in contrast to the results published by Ball et al

 The linezolid PA program described in the present analysis denied linezolid insurance coverage at the point of sale, requiring prescribers to submit clinical documentation demonstrating a need for linezolid. Upon PA approval, the linezolid claim was adjudicated as a formulary agent with cost shares of $15 to $35. In the current study, member cost share was $15 to $35 in both the intervention and comparison groups and therefore likely had no impact on linezolid utilization.

Two important characteristics of this study are worth noting. First, we studied a commercial population exposed to an appropriate-use PA program, while other research was focused on member OOP linezolid costs among Medicare Advantage Plan members. Population differences could account for discrepant results, in that our average age was lower and older adult members could have been at higher risk for incurring increased costs and higher hospitalization rates. Second, it is also possible that these populations had different indications for linezolid treatment, whereas the Medicare members may have had more advanced infections. Nonetheless, the implementation of a linezolid PA was without negative medical consequences over a period of 30 and 60 days, and showed cost savings for the intervention group.

The foremost limitation of this study is its quasi-experimental design comparing 2 commercially insured populations without randomization. Although the group characteristics were similar at baseline, claims analyses are limited in their ability to account for many possible differences among individuals and prescribers. Second, the primary internal validity concern regarding the findings is the possibility of changes that may have occurred at the same time as the implementation of the PA policy, or that a sentinel effect exists affecting regional variations in health insurance coverage. We are unaware of any effects that could have changed prescribing patterns independent of the PA program at the time of the study. Third, we may have overestimated the prevalence of patients without antibiotic therapy due to the use of physician samples or cash payment for linezolid and/or other antibiotic therapy. Fourth, the study is limited in the assessment of provider costs associated with the time spent addressing the denied claim, including possibly submitting a medical exception request or providing alternate pharmacotherapy. Fifth, the generalizability of the current study fi ndings is limited to continuously enrolled, commercially insured individuals in the South and Midwest. Lastly, this study utilized administrative claims data that are used for payment purposes only and may not be representative of actual medical diagnosis or healthcare utilization.

Clinical programs aimed at appropriate use of drugs will remain a primary function of health insurers in the future. The findings of this study demonstrated a signifi cant savings associated with a linezolid PA program and failed to identify any difference in clinical outcomes between members who were or were not exposed to the linezolid PA program. Furthermore, resistance to linezolid has occurred, but it is uncommon. We still have a chance to reduce the contribution of linezolid to the growing epidemic of antibiotic resistance, and the current results would suggest we can reduce the use of linezolid without harming patient care. Future research should be directed toward studying clinical and total direct healthcare cost outcomes of utilization management programs.

This study demonstrated that a linezolid PA program did not appear to be associated with a negative impact on medical outcomes and was associated with lower costs.

A Linezolid Prior Authorization Program: Clinical and Economic Outcomes

Across the country today, our healthcare leaders are moving forward in an attempt to reengineer our healthcare system and drive much-needed improvements in access, coordination, quality, and cost-effectiveness of care delivered to our US citizens. As this reengineering unfolds, the pharmacy benefit management industry is also presented with an ideal opportunity to transform itself as a critical contributor in helping to drive these national objectives. In an effort to capture the untapped value that pharmacy benefit managers (PBMs) bring to the table and help guide this transformation, we have developed and introduce here the concept of “pharmacosynchrony.” Pharmacosynchrony represents the application of innovative clinical, analytic, and technologic pharmacy solutions to drive improved care coordination and a higher-quality, more patient-centric model of care.

It appears to have become universally accepted that the healthcare system in the United States is highly dysfunctional. Care remains highly fragmented and increasingly more complex, with a lack of coordination being the norm.

 Population management has still not been widely adopted except as needed for a few commonly reported Healthcare Effectiveness Data and Information Set (HEDIS) measures. Meaningful use legislation has led to a significant increase in implementation of electronic health records (EHRs), but the lack of health information exchanges limits flow of information.

 The Institute of Medicine’s seminal work, “Crossing the Quality Chasm,” states that all of the above leads to higher cost of care.

As a response, payers and providers are embracing newer healthcare delivery models as promising means of improving the healthcare system. Adoption of new models such as the patient centered medical home (PCMH) and the accountable care organization (ACO) is being accelerated by healthcare reform. PCMH has become defined as a full-service primary care practice model that supports integrated care, with emphasis on quality improvement, care coordination, and population management.

 ACOs are integrated units that coordinate primary and secondary care across inpatient and outpatient domains and are dedicated to population management for chronic disease. They are built to enhance cost effi ciency through reduced waste and to drive improved outcomes through tighter care coordination.

Early evidence is encouraging enhanced adoption of these models across market sectors, demonstrating that both PCMHs and ACOs can produce better-quality outcomes with lower costs.

Currently, fewer than 5500 practice sites are accredited by the National Committee for Quality Assurance (NCQA) as PCMHs.

 The Centers for Medicare & Medicaid Services (CMS) initially identified only 32 organizations nationally with the experience and maturity to be included in its Pioneer ACO program to test provider organizations’ ability to bear high levels of shared savings and risk.

While this transformation is encouraging, most of the provider community lacks appropriate infrastructure to support the underlying functions that turn a traditional practice into a PCMH or ACO.

 Most physicians do not practice on a site that can support these functions, and contracting entities such as independent physician associations have not fi lled this void. Consolidation in the provider market may be changing this dynamic, but current estimates are that the majority of healthcare is provided in offices of 1 or 2 physicians.

Currently, PBMs perform many functions for the safe and effective use of medications, including managing the preferred drug list or formulary, processing prescription claims and payment for insurance, controlling prescription costs, and utilizing programs to limit inappropriate medication use. The PBM’s existing programs, claims, and communications platforms put them in the best position to support the strategic objectives set forth by health plans, provider groups, and health systems as they transition toward more sophisticated delivery models. Expansion of PBM services to increase value for patients and providers has included reducing barriers to initiating medications for chronic illnesses, improving adherence for chronic medications, and encouraging cost-effective medication use by suggesting generic medications and formulary compliance.

 PBMs need to advance their role in the delivery of healthcare during this time of dramatic change in the US healthcare system. Change is necessary to improve medication use and avoid adverse events, expand connectivity to real-time prescription use, enhance reporting to evaluate patient outcomes, and leverage the clinical resources of PBMs to improve medication use by harnessing the data and making them accessible to healthcare providers.

Development of the PCMH and ACO infrastructure is a key opportunity for PBMs. Approximately 75% of healthcare costs in the United States today are driven by chronic illnesses including diabetes, cardiovascular disease, stroke, and cancer.

 Pharmaceuticals represent the most powerful tools in effectively managing these conditions, decreasing their progression, and improving overall patient functionality and quality of life. While new models of care are adopted, more comprehensive and advanced means of managing prescription drug therapy remain widely overlooked and undervalued as components of these models.

Our concept of pharmacosynchrony represents a compilation of tools and services by which the PBM industry can foster improved levels of partnership with managed care clients and the provider community to support improved care coordination in a more comprehensive, largely virtual manner. Improved care coordination is the cornerstone of healthcare reform and population-based health management. Key to this partnership is the PBM’s ability to leverage advanced information technology (IT) platforms while marrying such platforms with comprehensive clinical resources and expertise.

 The healthcare system of the future will find much less value in the traditional business model of the PBM serving primarily as the processor of prescription drug claims and providing basic clinical programming and analytics to manage prescription utilization only. In the world of the PCMH and ACO, the PBM will be expected to develop new levels of clinical programming, information exchange, and analytics to provide a much more robust and holistic level of support and service. The PBM must develop new means of connectivity with the provider and patient community to facilitate improved education and engagement in evidence-based standards of care.

Sophisticated data warehousing and analytics capabilities enable the PBM to perform the activities which assist health plan clients and providers with care coordination. Foremost, the PBM can employ well-validated risk adjustment methodology to claims data to assist providers in better pinpointing patients at higher risk of negative clinical outcomes. This will enable providers to more effectively target patients in need of closer follow-up and support a more judicious allocation of resources for clinical intervention. Effectively analyzed claims data will uncover patterns of prescriber and patient behavior, representing opportunities for education and intervention. A PBM’s ability to integrate and effectively analyze both medical and pharmacy claims activity in a near-real-time fashion enhances these aforementioned activities, while also assisting with monitoring timely improvements in important quality metrics such as pharmacy-based HEDIS performance measures.

The current PBM model includes electronic communication with pharmacies, plans, and employer customers. To fill the void in the new delivery systems, the PBM must improve connectivity with the provider and patient communities via new vehicles such as the Web, mobile technology, and EHRs.

 Each will improve timely access to key data and information, such as patient-specific clinical alerts, permitting more proactive intervention. Improved connectivity and coordination of care can also help to prevent negative clinical complications and their associated higher expenditures. Lastly, continuous development and refinement of key quality-based performance metrics and reporting can assist in monitoring and benchmarking provider care and support new methods of quality-based payment reform.

Postdischarge medication reconciliation is another key means by which PBMs can support provider organizations and payers seeking to improve quality while lowering costs. Today, up to 20% of patients discharged from our nation’s hospitals are readmitted within 30 days.

 Communication strategies will be developed to enable the provider, health system, or payer to notify the PBM regarding an impending hospital discharge, by perhaps focusing on diagnoses associated with high rates of hospital readmission. The PBM could then utilize its call center resources, including appropriate clinical personnel, to conduct a real-time medication reconciliation with the patient and/ or caregiver within 48 hours of discharge. This reconciliation process will comparatively assess pre- and postdischarge medications on hand in the home, including over-the-counter medications, to ensure adequate patient understanding of these medications and their appropriate use.

This review would also encompass an evaluation of duplicate therapy, polypharmacy issues, potential drug-drug interactions, proper dosing, and appropriate prescribing and filling of postdischarge medications in accordance with national consensus guidelines and best practices.

 The PBM’s unique position of having pre- and postadmission medication claims simplifies the process and reduces patient confusion about complicated regimens.

 Medication reconciliation is now a Joint Commission National Patient Safety Goal and has been included in the CMS Provider Quality Reporting System, primarily because it has been demonstrated to improve quality of care through reduced medication errors and decreased readmission rates.

The PBM also represents an ideal partner with providers on population management and the goal of continuous quality improvement. Pharmacy claims data serve as a powerful resource to identify multiple types of care issues. No entity is in a better position to identify medication-free gaps between prescription refills or adherence issues. Additionally, claims data can be used to screen patient regimens for appropriate care in accordance with national and international standards of care and best practices. For example, the PBM can serve as an integral resource toward identification of patients with diabetes mellitus who are not receiving appropriate medications for renal and cardiovascular protection in accordance with American Diabetes Association guidelines, or patients with chronic obstructive pulmonary disease (COPD) whose prescriptions are not consistent with the current Global Initiative for Chronic Obstructive Lung Disease guidelines. Proper prescribing per disease state can be monitored and reported upon wherever there is significant clinical consensus as to the appropriate course of action.

The PBM is also in an ideal position to notify clinicians about prescriptions that have been transmitted to pharmacies but were never picked up by the patient (“primary” nonadherence). Electronic or e-prescribing transaction records and pharmacy claims activity documenting “reversed” claims (prescriptions returned to stock at the pharmacy due to lack of patient pickup), serve as key means to identify this type of nonadherence. Enhanced connectivity with provider offi ces allowing Web-based access to real-time, patient-specific medication dispensing history can also give clinicians newer and more valued insights into how their patients use their medications.

The PBM can build upon the existing communication loop with the patient and provider. Incorporating PBM clinical staff as members of the care team can also play an important role in better measuring key clinical performance metrics, supporting drug information needs of other team members, and more actively engaging patients between clinical visits on healthy behaviors and care plans. Patient outreach for any quality purpose and the result of each medication reconciliation must be captured appropriately and provided back to the care team in as timely and effi cient a manner possible. PBM-based Web portals can be used as a key vehicle to house these important data, to collect Health Risk Assessment (HRA) information from the patients, and in reporting. The use of IT systems to integrate medical and pharmacy claims, adherence information, and HRA tools allows for the PBM to identify the highest risk patients and provide that information regularly to the care coordination teams for better allocation of resources.

The PBM also has numerous tools at its disposal to deliver a more personalized approach to patient care. Existing resources such as call centers, Web portals, mobile technology, and decentralized clinical staff can surround the patient and provider with a variety of support services. Targeting high-risk patients for outreach for disease-specific coaching will drive more effective education and improve quality. Patients can be contacted when it appears that their regimen may be missing key components, such as the patient with diabetes not on a key medication as discussed above. High-risk patients can also be contacted when a prescription goes unfi lled to determine what the barrier may be and how it can be overcome. Innovative rewards-based programming can be established via drug benefit design to promote improvements in adherence and preventive care, such as vaccinations, smoking cessation, and routine lab monitoring. Of course, the medication reconciliation function described earlier is also a key example of a more personalized approach to care coordination and quality improvement.

The PBM can further support the transition of care by collaboratively developing and providing the necessary data and reporting to the clinician groups and health plans. These can be as simple as traditional reports looking at generic prescribing, to as complex as patient-specific gaps in care analyses and provider-based “report cards,” comparing individual physician prescribing patterns with those of their peers and benchmarking best practices across a wide range of metrics. These should include quality metrics as well as cost, by supporting measures such as proper asthma and COPD prescribing. Antibiotic use should be monitored and addressed if found to be at odds with practice guidelines. Specialists’ prescribing should also be monitored so that primary care physicians participating in PCMH and ACO models can better evaluate their choice of specialist partners.

All of the above represent key changes in the PBM service model that should drive improved quality and lead to cost savings. The PBM should not lose sight of the fact that traditional pharmacy benefit design also represents opportunity for change and improvement in supporting this paradigm shift. Today’s pharmacy benefit needs to be designed intelligently to encourage cost-effective medication use. Real-time e-prescribing tools simplify the prescribing process and guide decision making for clinicians. Automating drug utilization management tools such as step therapy and prior authorization helps reduce administrative burden for providers, thereby freeing time for more quality-based initiatives. Identification of patients who are underutilizing medications will lead to better, more costeffective disease management for their chronic conditions.

To achieve all of the aforementioned objectives will not be a simple undertaking. A more competitive and demanding marketplace will compound the challenge facing the PBM industry to make the necessary investments in IT resources. IT vendors such as those providing EHRs, e-prescribing platforms, medical claims processing, and laboratory data management must be open to collaborating with the PBM to openly share data and information in a consistent fashion. PBM clients such as health plans, large employers, and state agencies must also embrace the clinical and economic value of enhanced data sharing and integration with the PBMs. The provider community must be willing to embrace PBM personnel and systems as a key component of the newly evolving healthcare delivery team and alter practice patterns to capitalize on advanced sharing of key information and data from PBM providers. Currently, there is a paucity of evidence demonstrating patient benefits achieved with these new advanced clinical services from PBMs. Studies on patient outcomes with the new expanded services will need to be performed.

In short, the concept of pharmacosynchrony moves the PBM industry away from its traditional role as an administrative support resource for payers in managing pharmacy benefi ts. Pharmacosynchrony unleashes the underused power of pharmacy data, advanced IT systems, and comprehensive clinical resources to drive the PBM industry into a closer relationship with health plans, employers, provider systems, and patients. It provides these entities with a multidimensional suite of tools and resources to better manage drug therapy to attain better healthcare, better health outcomes, and lower costs. Only through this foundational shift in functional capacity will the PBM industry attain the type of alliance with its industry partners that will inevitably help to drive this nation’s healthcare to higher levels of quality and cost-effi ciency. In doing so, the industry will also engender the opportunity to earn a higher standing within the US healthcare system and within society as a pivotal resource in driving positive change.

Pharmacosynchrony is the application of innovative clinical, analytic, and technologic pharmacy solutions to drive improved care coordination and higher-quality, more patient-centered care.

Pharmacosynchrony: Road Map to Transformation in Pharmacy Benefit Management

Poor admission medication reconciliation can follow a patient throughout his or her hospital stay and can be a major contributor to medication errors. Poor discharge planning and medication reconciliation can result in diminished quality of care, deficiencies in medication use, patient injury, and increased cost of care.

Consider the following: approximately 20% of patients experience adverse events (AEs) within 3 weeks of discharge

; nearly 1 in 3 heart failure patients is readmitted within 1 month after hospital discharge

; and 3 of every 4 postdischarge follow-up visits occur without the benefit of a discharge summary.

 A 2011 study revealed that among 564 patients discharged from a hospital to a subacute care facility, 181 (32%) had pending laboratory tests.

 Of these, only 20 (11%) of the discharge summaries provided documentation of these pending tests. Other studies have also reported relatively poor documentation of tests pending at discharge.

The outcomes of poor transitions in care and discharge planning are shown in 

 Medicare patients readmitted to the hospital within 30 days of discharge (19.6%) cost the US healthcare system roughly $15 billion each year.

 The Agency for Healthcare Research and Quality (AHRQ) found a $412 per patient cost savings associated with patients who had a clear understanding of their hospital discharge instructions and medication use compared with patients who did not understand their instructions well.

The major reasons for poor discharge are system failures, inattention to the importance of medication reconciliation, lax standards, and poor information technology (IT).

 Direct communication between hospitalists and primary care physicians (PCPs) occurs in less than 20% of hospitalizations, and discharge summaries are available at less than 34% of first postdischarge visits.

 Inadequate communication between physicians, hospitalists, PCPs, and consultants also contributes to medication errors and potentially avoidable hospital readmissions.

In the past, a hospital receiving full payment despite its poor procedures for discharge had no incentive to improve. Even though The Joint Commission requires discharge summaries to be completed within 30 days, until now, no requirement existed to document pending tests. And IT vendors have had no incentive to create systems that can communicate with one another in this area. However, this scenario is changing rapidly, and hospitals will need to do what is right for patients and be prepared to comply with regulatory changes.

From the viewpoint of the hospital, the discharge medication process should be improved to: (1) assure that discharge prescriptions contain no errors by reconciling them with the inpatient medication orders and the patient’s prescriptions prior to admission; (2) capture all discharge prescriptions (if operating a hospital-owned ambulatory pharmacy) to improve revenue and improved outcomes; (3) educate patients on the importance of taking their medications on the schedule prescribed; and (4) reinforce with patients the importance of seeing their PCPs within 14 days of discharge. All of these actions have been shown to decrease hospital readmissions. This is a goal for which every institution is striving.

Since part of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores are calculated based on a patient’s education on newly prescribed medication and the intensity of AEs from these medications, the hospital has added incentive to ensure its discharge process is optimal.

Medication reconciliation is the process of comparing a patient’s new medication orders with all the medications the patient had been taking prior to changing levels of care. These changes in levels of care occur as the patient moves through the healthcare system; from home to the emergency department (ED), from the ED to an inpatient bed, from a general medical-surgical unit to an intensive care unit (ICU) or vice versa, from the ICU to surgery, and from the hospital back to home or to an extended care facility. Care must be taken at each of these transitions to avoid drug-related errors (eg, through omission, commission, duplication).

At the time of admission to the hospital, the steps include: (1) determining precisely the medications the patient was taking at home (home meds) and how the patient was taking them (ie, dosages, frequency, compliance); (2) determining which of the previous home meds must be continued while in the hospital or at the next level of care; and (3) determining what new medications the patient needs to receive in the hospital or at the next level of care.

At discharge, the steps include: (1) determining the postdischarge medication regimen based upon previous home meds, new medications received in the hospital or next level of care, and the new going-home (discharge) medication regimen; (2) developing discharge instructions for the patient for home medications; (3) educating the patient; and (4) transmitting the medication list to the follow-up physician. Oftentimes, the problem is that this process is not standardized and there are 2 to 3 different disciplines involved in the process, resulting in inconsistency.

A pharmacist’s input into the admission and discharge medication reconciliation process can yield substantial results. Verbal, written, or electronic contact between a hospital pharmacist and the patient’s community pharmacist is the ideal. One study discovered that medication discrepancies at discharge were disturbingly common without pharmacist reconciliation, identifi ed in 59.6% of patients.

Implementation of a pharmacist-facilitated discharge process increased recognition and resolution of these errors. Follow-up telephone calls enabled pharmacists to reinforce discharge instructions and promoted early recognition and resolution of postdischarge medication-related problems in patients taking more than 5 medications with at least 1 high-risk medication.

Several procedures can make the discharge process work better. One is the development of content and process standards, including a discharge checklist for hospitalists.

 The checklist should detail the processes and elements required for ideal discharge of patients. Refining the checklist for patients with specific diagnoses, specific ages, or specific discharge destinations may work even better.

Transferring important information from one provider to another is critical for improving transitions. However, even if discharge information is moved to the right places at the right times, there is the question of who is responsible for following up on the laboratory tests pending at discharge. There are 2 ways of handling this: (1) the inpatient provider completes his or her tasks at discharge and the responsibility then falls to the next provider to complete any pending tasks or tests at discharge; or (2) the inpatient provider retains responsibility for following up on any tasks or tests that he or she requested until all test results have been returned or the patient has made formal contact with the follow-up provider.

If there is one transition of care problem that stands out, it is the “revolving door” of re-hospitalization from nursing facilities. About 40% of Medicare patients discharged from hospitals are admitted to a skilled nursing or rehab facility to complete their recovery. But within 30 days nearly 1 in 5 of these patients winds up back in the hospital.

 This revolving door problem cost Medicare $4.34 billion in 2006. Especially in an elderly population, cycling in and out of hospitals can be emotionally upsetting and can increase the likelihood of medical errors related to poor coordination of care.

Several types of technologies have the potential to support postacute transitions and interventions (

These technologies can assist with improving medication adherence and reconciliation, patient monitoring, risk assessment, and other important aspects of care transitions. They can also help with communications between and among clinicians, patients, and informal caregivers. Unfortunately, these technologies are often underutilized even though they are widely available. Based on large-scale studies, care coordination supported by medical devices and computer-based technologies can lead to fewer hospitalizations and ED visits, higher patient satisfaction and acceptance, and reductions in the cost of care.

Performance measurement is one strategy with potential for improving the quality of transitional care. A valid and reliable self-report measure of the quality of care transitions that is consistent with the concept of patientcenteredness, and useful for the purpose of performance measurement and quality improvement, is available.

 The Care Transitions Measure (CTM) is a 15-item unidimensional measure of the quality of preparation for care transitions. The CTM discriminates between patients discharged from the hospital that did or did not have a subsequent ED visit or rehospitalization for their index condition. CTM scores vary signifi cantly among healthcare facilities that are known to vary in level of system integration. These scores also provide information useful to clinicians, hospital administrators, quality improvement entities, and third-party payers.

By training, pharmacy professionals have the most extensive background for successful medication reconciliation. Pharmacy technicians can also play a significant role in facilitating the medication reconciliation process. Current literature recognizes the value that pharmacy technicians bring to this process. A number of studies have confi rmed that well-trained pharmacy technicians under the supervision and support of pharmacists are the best choice for performing admission medication histories.

 Traditionally, prescribers and mid-level practitioners have struggled with completing medication history documentation on admission as well as reconciliation on discharge because it is labor intensive and often requires contacting 1 or more pharmacies for information. Also, it detracts from their availability for direct patient care. In addition, gathering the list of home meds is generally considered suboptimal use of physician and mid-level provider time. As with most processes, a small core group of welltrained individuals can ensure consistency and oversight.

Financially, pharmacy technicians offer an advantage over other healthcare providers in performing medication reconciliation functions. On average, 15 to 20 minutes is required to conduct and document a meaningful review of home meds. The cost for other healthcare providers to perform admission medication histories ranges from 2 to 6 times more than the cost of using pharmacy technicians.

		Pharmacy technicians—$5 per admission

		Physicians—$32 per admission (NP indicates nurse practitioner; PA, physician assistant; RN, resident nurse).

Pharmacists can be utilized as the responsible professionals to supervise the pharmacy technicians and pharmacy students in the performance of medication reconciliation activities. When medication histories are conducted and documented correctly and completely at the time of admission, the medication reconciliation process during the remainder of the patient’s stay is more efficient, more accurate, and therefore consistently safer. Medication reconciliation between levels of care (eg, to and from the operating room and/or ICU) also becomes a much simpler process.

Upon discharge, pharmacy technicians can again play a signifi cant role in assuring patient safety and in the thorough discharge medication reconciliation process. Although the pharmacist would have final responsibility for the discharge medication reconciliation sign-off, pharmacy technicians can be extremely valuable for reviewing, clarifying, and reconciling discrepancies between the admission medication history, the various inpatient orders, and the physician’s final discharge prescriptions.

Successful performance of medication reconciliation can have a positive impact on patient response to a hospital stay as well as support improvement in clinical quality and financial outcome.

March/April 2014

Recent Trends in the Treatment of Chronic Hepatitis C

Making the Marketplace More Patient Focused

A Linezolid Prior Authorization Program: Clinical and Economic Outcomes

Pharmacosynchrony: Road Map to Transformation in Pharmacy Benefit Management

Importance of Medication Reconciliation in the Continuum of Care

The Ongoing Challenge of Pain Medications

Letters to the Editor