Managed pharmacy

Statins Too Often Not Taken as Directed To Prevent a Second Heart Attack

Use of statins to prevent the recurrence of a heart attack after the first such incidence is a generally accepted practice guideline, but its effectiveness is muted because of nonadherence, according to a study in JAMA Cardiology.

Pharmaceutical Companies Get More Leeway To Discuss Off-Label Uses of Drugs Under Bill

The debate over just what a pharmaceutical company can say about off-label use of its medications pits free speech rights against the FDA’s mission to protect the public, STAT reports. A bill introduced by Rep.

The Formulary Files

Too many pills means lower adherence to antiretrovirals in HIV patients

Although adherence rates among HIV/AIDS patients are as low as 50%, anything less than 100% is unacceptable because adherence to antiretroviral therapy (ART) is the primary factor that determines virologic suppression, disease progression, and even death. Therefore, evidence-based interventions to improve adherence have become a focus of formulary decision makers.

One such intervention, known as regimen simplification, was studied in a meta-analysis published in January 2014 in Clinical Infectious Diseases. This meta-analysis of 19 trials evaluated the effect of pill burden (number of pills and other dosage forms) and dosing frequency, two major components of regimen simplification, on adherence in HIV-infected adults. Researchers concluded that while lower pill burden was associated with better adherence, once-daily dosing only slightly improved adherence compared with twice-daily dosing. This suggests that regimen simplification is an important consideration when making formulary decisions.

Slightly higher adherence among patients on once-daily regimen compared to twice-daily regimen

Source: Nachega, et al, Lower Pill Burden and Once-daily Dosing Antiretroviral Treatment Regimens for HIV Infection: A Meta-Analysis of Randomized Controlled Trials. Clin Infect Dis. 2014; 48:383–488

Krishna Rutvij Patel, PharmD

A Conversation With F. Randy Vogenberg, PhD, RPh: Changing Market for Pharmacy Benefits

Tight budgets and an increasing influx of expensive biologic drugs make it imperative to rethink risk management

At a time when health care reform is uncertain and hard-to-categorize biological drugs are becoming a greater share of overall costs, health plan medical and pharmacy directors have the opportunity to help reinvent how health care is paid for, says F. Randy Vogenberg, PhD, RPh. A pharmaceutical consultant to employers, hospitals, drug companies, and insurers, Vogenberg’s Sharon, Mass.-based firm is called the Institute for Integrated Healthcare.

One of his goals is to get people to think about the big picture.

“Extraordinarily expensive drugs are becoming available on a mainstream basis,” he says. “How are we going to finance them when our insurance industry was designed for the marketplace of the 1950s and 1960s to pay for hospital expenses, not for drugs? What is insurance and the management of risk going to look like in 5 or 10 years?”

Vogenberg is a senior fellow at the Jefferson School of Population Health at Thomas Jefferson University in Philadelphia, and was the strategic pharmacy adviser for the Value Based Pharmacy Purchasing Program for the National Business Coalition on Health that continues through the Mid Atlantic Business Group on Health. He is an adjunct faculty member at the University of Rhode Island College of Pharmacy and author of “Pharmacy Benefits: Plan Design and Management,” published in 2011 by the International Foundation of Employee Benefit Plans. He previously was a national practice leader for Aon Consulting (now Aon Hewitt). Vogenberg earned a bachelor’s degree in pharmacy from the University of Rhode Island and a PhD in health care management from Century University in Albuquerque, N.M. He completed a pharmacy residency at the Brigham & Women’s Hospital and Harvard Medical School in Boston. He spoke recently with Managed Care editor John Marcille.

Managed Care: What are payers doing right — and wrong — when it comes to paying for pharmaceuticals?

F. Randy Vogenberg, PhD, RPH: Health plans are all in some form of transition because of the economic recession, health care reform, and state reactions to federal health care reform. They are not really sure what they are supposed to be doing other than making health coverage more cost-effective. The problem with the coverage of drugs is that this future driver of costs is more on the medical side than it is on the pharmacy side. So the tactical things that health plans have done well in the past — processing claims, managing coverage provisions, and making sure that people get their cards on time — are not solely going to determine success. They are going to have to rethink how to execute coverage.

MC: What is changing?

Vogenberg: Because biologic and specialty drugs cross over pharmacy and medical coverage along with new MLR rules, we have seen a movement by national plans to either take the pharmacy benefit management functions in-house or create long-term relationships that dovetail PBM activity with the rest of what the health plan is trying to do. There’s a more holistic view of how they are handling pharmacy in conjunction with their medical coverage. Smaller, regional plans are still struggling with how to integrate medical coverage and pharmacy coverage. But even if coverage is separate, health plans are beginning to make decisions on a more integrated basis. Pharmacy directors and medical directors are working more closely to figure out the best way to handle coverage for different medications.

MC: Which plans are out front?

Vogenberg: It’s more about the people than the plans, because it’s the execution of the plan that is really important. Plans that have done a good job have had long-term stability in medical and pharmacy leadership. Kaiser Permanente, HealthPartners, Harvard Pilgrim Health Care, Fallon Community Health Plan, and CareFirst BlueCross BlueShield are examples of where there has been a lot of dialog and thoughtfulness about making changes in a way that does not cause too much disruption to providers and patient.

MC: What specific efforts are heading in the right direction, and do they relate to the “holistic value proposition” that you have written about?

Vogenberg: The holistic value proposition has typically been interpreted by health plans as value equaling cost. From an employer’s perspective — and this is becoming more true for unions and municipalities as well — cost is important, but what’s more important is the overall effect on patient care, both cost and quality. The broader view of how you balance caring for plan members during periods of wellness and periods of illness has become more of a focus. So to what extent do drugs contribute to improving the health status of the patient along that continuum, and how do you address various risk factors impacting health status? Many plans struggle with that because they can’t control many of the elements in the delivery of care.

“Biologics are about 20 to 30 percent of drug expenditures.... [By 2015] the pharmacy benefit is going to be driven by biologic use.”

MC: We aren’t hearing much about how the Affordable Care Act’s provisions will affect pharmacy costs. Am I overlooking something?

Vogenberg: No, you’re right. That’s one of the big holes in this. The focus has been on hospital and physician costs along with sites of care. But only about half of what employers spend on health care goes to health plans. The other half is being managed somehow by the employer through workers’ compensation, occupational health, and onsite medical clinics.

MC: Are the employer coalitions doing something to integrate all of these strands?

Vogenberg: It’s actually gone the other way in general. Health plans have avoided workers’ compensation, disability, and those kinds of programs. Local hospitals and some of the private insurers, like Liberty Mutual, Aflac and other smaller companies, have dominated that space. It raises the question: If we are moving toward the concept of global health care, why aren’t we looking at 100 percent of the health care dollars being spent? In Pittsburgh, you have a marketplace that has been turned upside down with Highmark Blue Cross Blue Shield buying West Penn Allegheny Health System and the provider network UPMC, creating an insurance entity. That’s probably going to play out in a lot of urban areas. Insurers will then have providers who could do occupational health, for example.

MC: Is occupational health that easy to integrate with the traditional medical care?

Vogenberg: Because of the way these systems have all grown up in this country, there are different sets of laws and requirements in each state. Ultimately not just health plans, but state governments along with the feds are going to have to come to grips with what they are going to do about how workers’ compensation, disability, and occupational health fit into the whole care continuum.

MC: Is much work being done on this, or is it still on the horizon?

Vogenberg: It’s mostly still on the horizon. The Pittsburgh market is beginning to look at this and say, How can we build a different model? Highmark is an example of doing something very different and unexpected from a plan. Most health plans move incrementally from year to year, but they are going to have to be more aggressive because they are not going to have the luxury of time, nor economic resources.

MC: Do you have an example?

Vogenberg: Pathways have always been a relatively passive tool, but we are seeing pathways being done in a way that’s much more aggressive, controlling and directive. That’s been disruptive.

MC: We spoke with Dr. Lee Newcomer, senior vice president for oncology, women’s health, and genetics at UnitedHealthcare, which is doing bundled payments for oncology care. What are your thoughts on that approach?

Vogenberg: Most insurers are looking at oncology as the bellwether for how to create change. United is getting at how to deal with the buy-and-bill problem without having your provider network run away from you. Some of the regional plans have done that by pushing money down to their networks, saying, “OK, you figure it out. Twenty percent of your payment will be based on quality measures.”

MC: Is it moving beyond oncology?

Vogenberg: Yes. Health plans are looking at orthopedics and immunology, rheumatoid arthritis as a diagnosis. They are trying different ways to work with their specialty clinician network providers to figure out how to more effectively and efficiently get to the endgame that everybody wants, which is cost-effective, high-quality care.

MC: Which health plans are showing promise?

Vogenberg: One of the problems we have in health care is that people tend to not share what they’re doing much anymore. They are not writing articles and they are not presenting at conferences as much. Dr. Newcomer has been out there, and CareFirst is an example of an insurer that is using a combination of incremental thinking with some disruption. It has done it with oncology and is now going to expand it out to some of the other medical specialties. They are working with their physician network and building reimbursement contracts that align the incentives between the different groups, and it gets away from that buy-and-bill mentality. The big question is trying to figure out what is going to stick and survive in the long run.

MC: Are some of the older ideas sticking, such as reducing costs for drugs that help people keep chronic diseases under control?

Vogenberg: Health plans have to stop worrying about churning in their own plan and look at it more as a community. When it comes to improving cost and outcomes, much of the focus is still on opportunities for short-term return on investment, such as what you would see with diabetes and with asthma.

MC: What other strategies have been working?

Vogenberg: Everyone has done a good job at pushing generic utilization as much as they can, taking advantage of the drugs going off patent. When we look at that in the context of taking away potential financial barriers to patients, making generic drugs more accessible will deliver better cost outcomes.

MC: What about biosimilars?

Vogenberg: The transition from traditional chemical-based drugs to biologic-based drugs will be driving the market, and that’s going to affect the total cost of care over the next five years. Biologics are more complicated and expensive to make, so that creates a built-in barrier to coming out with biosimilars or biogenerics. Many biologics have gone off patent and nobody is even talking about making biogenerics today because the market is too small.

MC: What percentage of the drug expenditure today is on biologics?

Vogenberg: Biologics are about 20 to 30 percent, and the estimate is that they will be about half by 2015, depending on what drugs actually get through FDA approval. So in a pretty short period, the pharmacy benefit is going to be driven by biologic use. They also represent an increasingly significant percentage of the medical spend, especially in oncology. By 2015, which coincides with health reform implementation, they will make up about a third of medical spend.

MC: So this is the tiger in the room.

Vogenberg: It’s the 800-pound gorilla. Employers are aware of it, but many don’t know the basics about what biologics are all about. They can’t get their arms around it in the way that they can understand traditional drugs. There’s a huge knowledge gap among self-insured employers about this whole area and the crossover between pharmacy and medical coverage.

MC: To what degree do employers contract directly with specialty pharmacies?

Vogenberg: Probably 90 percent of biologics are coming through some type of specialty pharmacy, for lack of a better term. The definitions in this area are still very fluid, and there really isn’t any good definition of a specialty drug, let alone a specialty pharmacy. Requirements from the manufacturers regarding how they distribute products complicate things even further.

MC: That sounds like a problem for insurers that want to provide these drugs to their members.

Vogenberg: Limiting distribution gives manufacturers more control over the information that they have to report to the FDA about the providers and patients who are using the drug. This was less of a problem when these were orphan drugs and maybe a couple thousand patients who needed them. But we have more mainstream biologic products today, involving diagnostics as well as drugs. This creates a big challenge for health plans in terms of access and price. But manufacturers are beginning to rethink what they are doing. As more products come through the pipeline, the current systems for distribution and contracting don’t make a lot of sense.

MC: What would make sense?

Vogenberg: To go to more of the open style that they’ve always had with drugs. The FDA’s Risk Evaluation and Mitigation Strategy — REMS — is more a politically driven program than a practical safety solution for patients, particularly as the market transforms into a biologics marketplace. There are many reasons why it makes sense to mainstream these products as long as pharmacies can follow up with patients. We’re also seeing a confluence with medication therapy management services. CareFirst is out front on that, wrapping MTM services around some of their specialty products. Biologics pretty much vindicate the point that manufacturers have been making for a long time, that if you are using the right drug for the right patient for the right reasons, then it can be a cost-effective solution in terms of the total cost of care. But if the patient doesn’t use the drug, then you’ve lost that value proposition.

MC: Do you see a time when payers are just not going to pay for the most expensive drugs because they can’t afford it, regardless of the benefit to the patient?

Vogenberg: That’s where we’re heading. We used to have extraordinarily expensive drugs to treat rare diseases, but this is now becoming a real issue on a mainstream basis. We have thousands of patients that potentially could be on these very expensive drugs, and there hasn’t been much time or attention given to how we can afford it.

MC: How are health plans going to keep up?

Vogenberg: Health plans are overwhelmed with all of the change that is happening at a time when there is tremendous fiscal restraint. They are not able to raise premiums. They are stuck with cutting personnel and trying to offload risk to provider networks as a way of figuring out how they can manage all of this change while technology is driving up costs. It’s an extremely challenging time for health plans.

MC: What do you recommend they do?

Vogenberg: Health plans need to find and support innovative solutions or they are going to get stuck with whatever is in the marketplace. There’s a short window — maybe a couple of years — where they have a chance to co-develop new strategies with self-insureds, not just tactics, for dealing with what’s happening with pharma

MC: What will be the biggest challenge to health plans’ pharmacy and medical directors?

Vogenberg: Dealing with day-to-day responsibilities versus creating this future vision. You can really get stuck in the tactical execution of health plan operations.

MC: Thank you.

John Marcille

New Hepatitis C Regimen Stimulates Changes in Therapy Management

Costly protease inhibitors work well in many patients, but call for careful monitoring

In less than a year, two new protease inhibitors — telaprevir (Incivek) and boceprevir (Victrelis) — have changed the standard of care for hepatitis C by introducing a new mechanism of action, but their significance goes beyond that.

They are the first new medications for the disease in 10 years and they have brought dramatic improvements in outcomes by knocking out this infection in many more patients, including previous poor responders. They have also complicated care by adding a third agent to the previous standard regimen of two agents.

The new agents are examples of how therapy management for new and costly medications is moving from traditional utilization and outcomes management to more sophisticated strategies. The focus on adherence and medication possession rates is giving way to patient selection criteria and close monitoring of clinical results.

Approximately 3.9 million people in the United States have chronic hepatitis C virus (HCV) infection, and about 5,000 acute cases surface annually.

Boceprevir and telaprevir are direct-acting agents that block the growth of viruses by directly disrupting essential viral functions. They were approved only as supplements to the previous standard treatment, a combination of ribavirin (Rebetol, Copegus) plus peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron).

Both are also approved only for use in one subset of patients: genotype 1 patients. HCV has at least 6 genotypes and 50 different subtypes, with genotype 1 being the most common.

In trials, the new drugs increased cure rates, known as sustained viral response (SVR) rates, by 30 to 40 percentage points over control groups receiving peginterferon and ribavirin. SVR means that no HCV is detected in the blood.

For telaprevir in one study, a SVR at 24 weeks was achieved in 75 percent of patients, compared with 44 percent for control patients. For boceprevir, in one study the success rate for triple therapy was 66 percent, compared with 38 percent for control patients.

Based on these results, the American Association for the Study of Liver Diseases updated its clinical guidelines to recommend triple therapy with a protease inhibitor, interferon, and ribavirin as the standard of treatment for hepatitis C.

David Lassen, PharmD

“We took a step back ... to make sure we could capitalize on the value of these medications,” says David Lassen, PharmD, chief clinical officer at Prime Therapeutics.

“The hope for improved outcomes produced an immediate demand for these medications,” says David Lassen, PharmD, chief clinical officer of Prime Therapeutics, a pharmacy benefit manager. “Previously the utilization of medications used to treat hepatitis C was on the decline, causing an overall decrease in the pharmacy cost trend over time. With the entrance of these two new agents, we have seen a significant increase in drug trend driven by increased use and cost.”

Doubling the cost of HCV management

An article in the November 2011 issue of the Journal of Managed Care Pharmacy by Prime’s pharmacy experts says that the new regimen will more than double the cost of HCV management. Telaprevir costs $49,200 for its 12-week regimen. The required peginterferon and ribavirin add $17,175 for 24 weeks and $34,349 for 48 weeks of therapy.

Boceprevir costs $26,410 for a 24-week duration and $35,213 for 32 weeks. Peginterferon and ribavirin add $20,037 or $34,349 to the total.


The protease inhibitors add to the complexity of treatment for hepatitis C. Poor response and anemia were problems with the previous peginterferon-ribavirin regimen.

Anemia has increased significantly with the new agents. In studies of telaprevir it increased from 17 percent to 36 percent, and in studies of boceprevir it increased from 20–30 percent to 45–50 percent. The increased anemia may stimulate more frequent therapy with erythropoiesis-stimulating agents, further driving up costs.

The new agents have many drug interactions, including conflicts with statins, and there are new side effects, such as the skin rash that is associated with telaprevir. This is in addition to flu-like symptoms that are associated with peginterferon.

There are other implications for the new medications. Both have demonstrated success and are approved for use in poor responders, so the demand for the new agents may spike until this cohort is resolved.

The new regimen requires monitoring of viral loads at specific points, and there are parameters for discontinuing therapy when treatment is futile.

Lassen says that Prime Therapeutics planned ahead to be able to handle the protease inhibitors. “In anticipation of the approvals we took a step back to revise our management strategies to be sure we could capitalize on the value of these medications in an evidence-based manner,” he says.

Prime Therapeutics made significant changes in its utilization and therapy management activities. It expanded the patient-specific data it captures. For initial authorizations, it asks about comorbidities such as HIV/AIDS and about the extent of liver disease. It also asks about previous treatments with protease inhibitors for HCV.

For renewing authorizations, the company is going further. “We are looking at the viral load component to ensure that the therapy is on track because some of the patients are not naïve to treatment,” says Lassen. Providers are asked to report the specific HCV RNA levels from lab tests at 4 or 12 weeks, depending on which new drug is being used.

While Prime, like other PBMs and even health plans, is interested in capturing more clinical data to improve its quality and cost management, Lassen emphasizes that this has to be done appropriately. “We were careful and thoughtful in our approach. Any request for additional information as part of prior authorization or utilization management can have a negative impact on providers.”

He adds: “It is also important that requests like lab results as part of renewals do not interrupt therapy. There can be legitimate delays in getting tests done, and we make it a point to provide continued coverage while tests are being arranged.”

For health plans

The protease inhibitors are game changers in the treatment of hepatitis C — the first new medications in 10 years with a new mechanism of action.

“Triple therapy is complex, “Lassen says. “Patients cannot be switched to a different agent once a course of therapy is started, and it is critical that therapy be completed. Up front, you need a clear set of criteria for patient selection, and then there needs to be close monitoring and a clear set of supportive care activities as patients move through therapy.”

How well did that new drug work?

Health plans and PBMs are collecting more patient-specific clinical data as part of their prior-authorization and therapy management. These data are increasingly important in ensuring the appropriate use of new, more complex, targeted medications.

The questions below are asked by Prime Therapeutics, a pharmacy benefit manager owned by several Blue Cross Blue Shield plans, when a renewal authorization is being considered for telaprevir (Incivek) and boceprevir (Victrelis). HCV RNA results indicate the level of hepatitis C infection and the progress of therapy.

The questions are taken from the prior-authorization form used by Blue Cross Blue Shield of Texas.

Incivek requests
Was the patient’s HCV RNA level measured at four weeks of treatment? ___ Yes ___ No
If yes, what was the viral load? _______ IU/mL
Victrelis requests
Was the patient’s HCV RNA level measured at 12 weeks of treatment? ___ Yes ___ No
If yes, what was the viral load? _______ IU/mL
Was the patient’s HCV RNA level measured at 24 weeks of treatment? ___ Yes ___ No
If yes, what was the viral load? _______ IU/mL
Thomas Reinke
Contributing Editor
Medication Management

Lipitor Kicks Off Onslaught of Drug Patent Conversions

Formulary design, contracting, and other strategies will be key to maximizing the opportunities of brand patent expirations

Lipitor’s anticipated patent expiration in November will be a blockbuster event in further tempering the escalation of pharmacy costs, but there may be other benefits.

Lipitor (atorvastatin) is the world’s biggest drug ever says George Van Antwerp, general manager for pharmacy solutions at Silverlink Communications. Its 2010 sales were $7.2 billion, and the availability of a generic will dramatically reduce expenditures for cholesterol-lowering agents.

The hidden value is that the strategies and actions taken to maximize savings from this conversion can serve as spring training for the world series of $78 billion in patent expirations scheduled through 2015 for preeminent names such as Plavix, Singulair, and Nexium.

Drug patent expirations 2012–2015

From now until 2015, at least 13 blockbuster drugs are scheduled to lose their patent protection. Health plans and PBMs can use Lipitor’s patent expiration to fine tune their plans for other upcoming conversions.

*Some of these totals differ from the sum of the columns because of rounding.
Source: IMS Health and T. Reinke

Converting an agent from protected status involves activities such as contracting with brand and generic manufacturers, changing formulary placement, counterdetailing in response to manufacturers’ preservation strategies, imposing new utilization management techniques, and engaging in consumer and provider education.

The specific tactics vary greatly from drug to drug, but Lipitor’s imminent change can sharpen skills and strategies that will be required for other upcoming conversions.

Converting Lipitor

“Cholesterol-lowering agents were the number one cost driver for our clients in 2009 and 2010, says Brett Kelly at Navitus Health Solutions, a national pharmacy benefit manager owned by the Dean Health Plan in Madison, Wis. “Our profile is 30 percent branded and 70 percent generic statins, and the cost of branded agents is $4 to $4.50 while the cost per day for the generic statin is $0.25.”

Sales of Lipitor decreased from $8.6 billion in 2006 to $7.2 billion in 2010 while sales of Crestor increased 189 percent from $1.3 billion to $3.8 billion. The sales of all other branded statins also fell, in part because of the availability of simvastatin — the generic of Zocor.

Statin prescriptions increased from 182 million in 2006 to 218 million in 2010. Simvastatin became a generic in 2007 and it has taken volume from all other statins except Crestor, which increased from 13 to 25 million scripts from 2006 through 2010.

The preferred formulary for statins could comprise only generic agents, with brand medications available on a non-preferred or step-through basis.

One statin strategy that experts foresee is a formulary transformation to generics. “With two higher-potency statin generics available, there is little justification to keep a branded agent in a preferred category,” says Kelly. “We expect that the brand statins will become disadvantaged, moving to the nonpreferred tier or requiring step-through [from a generic].”

“The goal is an 85–90 percent generic rate for statins next year,” says Kelly.

“Historically, over 90 percent of a brand’s volume will convert to its generic alternative,” says Van Antwerp. “And there is no reason that will not occur with Lipitor.”

Jan Berger, MD, chief medical officer at Silverlink Communications agrees. “At least 80 percent of people on statins can be effectively treated with what will be a full generic class. Only the super-high-risk, with recalcitrant lipidemia, which the literature says is 15–20 percent, will need a brand statin,” she says.

In addition, Berger predicts that generic atorvastatin will pull market share away from simvastatin.

The financial effect of Lipitor’s conversion is difficult to predict because the price of the generic is unknown.

Conversion strategies

Formulary design, utilization management strategies, and effective communication are key elements in planning for a drug’s conversion.

“The efficacy of different medications in a class affects formulary design and utilization management strategies for drugs losing their patents,” says Antwerp. He says that with statins, careful consideration must be given to whether Crestor can be excluded or moved to a nonpreferred tier. It has an FDA approval for atherosclerosis, which differentiates it from the others.


Plavix, which is anticipated to lose its patent protection in May 2012, is an interesting case in formulary design and utilization management, similar to Lipitor. Its 2010 sales were $5.8 billion, making it next year’s biggest patent loser. Express Scripts reports that in its book of business, Plavix has a market share of 87 percent among antiplatelet agents. A truly dominant position may make it easy to convert a drug class to an all-generic status next year.

Conversely, in therapeutic classes with several competing and differentiated agents, it may be more difficult to dramatically restrict the formulary.


Brett Kelly commented on Navitus’s strategies to capitalize on Lipitor’s impending fall from grace. “Our planning for Lipitor’s expiration started in 2010. In 2010, 50 percent of our clients had Lipitor as a preferred agent and 50 percent required a step-through. For 2011 we thought it would be wise to preemptively move patients to Lipitor in anticipation of it becoming a lower cost generic agent, so we advised our clients to make it a preferred agent with a tier 1 copayment, and a majority of them agreed to do that.”

This was the direct opposite of a widespread trend where Lipitor was being moved to non-preferred status.

Navitus’s formulary placement tactic is linked to a contracting strategy that is intended to drive down costs through the end of the six-month generic manufacturing exclusivity period.

Post-patent contracts were popular when Merck’s Zocor lost its patent.

A post-patent contract is important because it can provide some price protection to buyers for the uncertainties of the launch of a generic.

Van Antwerp says health plans and PBMs need to consider several other conversion issues. “Drug manufacturers usually implement strategies to preserve their medications, and these activities can start well in advance of the expiration dates,” says Antwerp. “Their activities can be wide ranging, such as consumer advertising, prescriber detailing, or discounting.”


Discounting of one sort or another is widespread among the brand statins. Pfizer provides a $4 copayment coupon. Zetia and Vytorin also have copayment discounts. Van Antwerp says health plans need to monitor the discounting and other marketing activities of all brand manufacturers in a class, not just the manufacturer whose product is going generic.

From now until the end of 2015, patent expirations are scheduled for at least 13 blockbuster medications and many smaller ones. Some classes, such as antidepressants, will see several blockbusters lose their patent protections. Pharmacy and medical directors at the health plans face abundant opportunities to shape formularies and they also have considerable work cut out for themselves.

Lipitor’s patent loss will hasten conversion of statins to generics

Lipitor’s patent will expire in 2011. Some experts have indicated that the volume of prescriptions for generic simvastatin has grown steadily while the volume of prescriptions for brand name agents, except Crestor, has declined.

Experts predict that the preferred formulary for statins could comprise all generic agents, with brand medications available on non-preferred or step-through basis.

Sales and prescription volume for cholesterol lowering agents

U.S. number of prescriptions by year (millions)

U.S. annual sales (millions of dollars)

Source: IMS Health

Contact the author at

Thomas Reinke
The Formulary Files

More PBMs used for dispensing, utilization review

PPOs are increasingly looking to managed pharmacy programs to help manage drug utilization costs of members with chronic conditions who are taking numerous medications. In general, the larger the PPO (number of members), the more likely it is to use a managed pharmacy program. The Sanofi-Aventis Managed Care Digest Series — HMO-PPO Digest 2010–2011 suggests that in 2009, more than 80 percent of PPOs with 500,000 to 999,999 members had a managed pharmacy program, compared with about a quarter of plans that had fewer than 20,000 members.

By far, the most prevalent managed pharmacy programs involve pharmacy benefit managers. PBMs are playing a greater role as they are involved in administration, dispensing, utilization review, and claims and mail-service processing, according to the report.

With their specialized services in tracking electronic prescribing and medical records, PBMs should be experiencing heightened demand — especially with recent health reform emphasizing the importance of health information technology. For example, PPOs are using PBMs to dispense medications, with 82 percent using PBMs for this service in 2009, up from 78 percent in 2008.

Utilization review had a slight downturn in 2009, says the report, after having a sharp rise from 63 percent in 2006 to 76 percent in 2008. In 2009, almost three-quarters of PPOs surveyed said they used PBMs to provide drug utilization reviews. But the report says PPO reliance on PBMs for drug utilization review is likely to increase, “especially as pay-for-performance and outcomes measures become more prominent in the post-reform era.”

Various services provided by PBMs to PPOs

Source: Sanofi-Aventis Managed Care Digest Series — HMO–PPO Digest 2010–2011


Formulary Management

Part D Model Guidelines Updated Far Too Infrequently

The static approach overseen by United States Pharmacopoeia shortchanges beneficiaries and benefit plans

As patients and their physicians go about the annual process of evaluating Medicare prescription drug plans, and as Medicare plan sponsors begin to develop formularies for plan year 2012, (and the Centers for Medicare & Medicaid Services (CMS) gears up to approve them), it is important to examine the current framework for the development of the only formulary classification system specifically developed for the Medicare drug benefit — the Medicare Model Guidelines.

Under the Medicare Modernization Act of 2003, the United States Pharmacopoeia (USP), under contract to the Department of Health and Human Services (HHS), is responsible for developing the Medicare Model Guidelines. The model guidelines list medication categories and classes.

By law, the Model Guidelines are recognized as a statutory safe harbor. Part D plan formularies that use categories and classes that are consistent with the Model Guidelines cannot be disapproved for participation in the Medicare Prescription Drug Program on the basis that they are likely to substantially discourage enrollment by certain Medicare beneficiaries.

In addition, the Model Guidelines:

  • Establish a framework for Medicare prescription drug plans that are required, by regulation, to include on their formularies at least two drugs for each distinct therapeutic category and pharmacologic class unless there is only one drug available in the class or category or one drug is clinically superior.
  • Establish the parameters for allowable midyear therapeutic substitutions within classes.
  • Are used by CMS during the formulary review process to identify formularies that may be outliers with respect to formulary coverage for Medicare plans and therefore require further evaluation.

Updating the model guidelines

USP initially reviewed and revised the Model Guidelines every year. However, after approval of version 4.0, USP and CMS moved to a three-year revision cycle. CMS approved Version 4.0 in February, 2008; it was effective for the plan year beginning Jan. 1, 2009. It remains in effect through Dec. 31, 2011. There has been no process for reviewing new drug approvals or newly approved therapeutic uses and no process for updating therapeutic categories or classes since Version 4.0 was approved.

In August 2010, USP began work on revisions for Version 5.0, and a new Model Guidelines expert committee began meeting to formulate recommendations to CMS. Public comments were solicited and the expert committee’s recommendations were submitted to CMS in January. Once approved by CMS, Version 5.0 will be in effect for 2012–14.

Prescription drug therapies are constantly evolving, and new drug therapies inevitably become available over the course of a single plan year. In fact, since approval of Model Guideline 4.0 in 2008, the Food and Drug Administration (FDA) has approved over 270 new drugs, of which at least 50 were new molecular entities. Thirty-four of these new approvals were given a high-priority review because, in the FDA’s words, they represent “significant improvement, compared to marketed products, in the treatment, diagnosis, or prevention of a disease.” Yet, lacking a process for continuous review, USP could not begin to review these drugs until last fall.

Because the process for updating the Model Guidelines begins a full year before the new Model Guidelines go into effect, depending on when the drugs received FDA approval, the gap between the time of approval and evaluation by USP for inclusion in the Medicare Model Guidelines can be up to four years. For example, there are several medications that are likely to be approved during 2011. None will be reviewed for inclusion in Version 5.0, even though Version 5.0 does not go into effect until Jan. 1, 2012.

If the existing policy remains in effect, Version 5.0 of the Model Guidelines, including the drug classes and categories, will remain unchanged until the plan year that begins Jan. 1, 2015. Drugs approved in 2011 will not be reviewed until at least the fall of 2013 and will not be added to the guidelines until Version 6.0 which will be effective for plan years beginning on Jan. 1, 2015 and ending Dec. 31, 2017.

Role of formularies

While a degree of formulary stability is important, formularies also must change to accommodate new drug approvals and new drug information. The dynamic nature of formularies is recognized in how they have been defined by leading authorities.

The “Principles of a Sound Formulary System,” a consensus document developed by a coalition of national organizations representing health care professionals, government, and business leaders, defines a drug formulary as “a continually updated list of medications and related information.... ” (The principles are at The Institute of Medicine defines a drug formulary as “a continually revised compilation of pharmaceuticals that meet pharmacopoeial standards.”

Best-practice formularies and formulary classification systems used by hospitals, health plans, government entities, and even Part D sponsors have processes that provide for continuous updating and review of formulary drugs and categories. For example, the American Hospital Formulary Service (AHFS) Pharmacologic Classification, widely used by hospitals, state Medicaid agencies, private insurers and Health Canada, is updated and published annually with intermediate updates published throughout the year.

The National Committee for Quality Assurance’s accreditation standards for managed care organizations, including Medicare Advantage plans, require that organizations review pharmaceutical management procedures, including formulary preferred pharmaceuticals, at least annually. The organization also must have a process for prompt response to member, pharmacist, or practitioner concerns regarding adding or deleting pharmaceuticals between annual reviews and must update procedures as it receives new pharmaceutical information without waiting for requests from members, pharmacists, or practitioners.

In 2000, the Institute of Medicine (IOM) found that the Veterans Administration’s blanket policy of waiting one year before considering any newly approved drugs for inclusion in the VA National Formulary “denied veterans access to some drugs the FDA finds significant, provides questionable protection from adverse events, and fosters a perception that it is a cost-based measure.” The IOM said that “the VA National Formulary should examine drugs newly approved by the FDA in a timely manner and abandon the blanket policy of a fixed waiting period.” Today, the VA National Formulary has processes to entertain formulary additions as well as drug class reviews on an on-going basis.

By law, USP must revise the Model Guidelines “from time to time to reflect changes in therapeutic uses covered by Part D drugs and the additions of new covered Part D drugs.” And while PDP sponsors are not permitted to change therapeutic categories and classes in a formulary other than at the beginning of the plan year, Congress explicitly allows more frequent changes “to take into account new therapeutic uses and newly approved covered Part D drugs.” However, USP is now only releasing guidelines every three years, a timetable that appears inconsistent with recognized best practices for updating and revising formularies and formulary classifications systems.

Notably, while the USP Model Guidelines were established by Congress to protect Medicare beneficiaries’ access to needed medications and serve as a safe harbor to promote a nondiscriminatory formulary classification system, it appears that plans have decreased their reliance on the guidelines as a model. At its highest usage in 2006, 74 percent of health plans were using the USP Model Guidelines (Version 1.0). According to CMS, in 2008, more than half of plans substituted their own classification system. Today it appears that health plans are even less likely to follow the USP Model Guidelines.

By law, individual plan sponsors are given broad discretion to develop their formularies, which has led to wide variation in the scope of formulary coverage across PDPs. Examining coverage of the top 10 brand-name drugs commonly used by Medicare beneficiaries, one researcher found that in 2010, only three of the top 10 commonly used drugs were on the formularies of all 43 national and near-national PDPs. This researcher found that while the average PDP formulary lists 87 percent of the drugs on CMS’s drug reference file, some plans cover as few as 62 percent of these drugs.

Provision of an adequate formulary

Yearly, CMS is responsible for reviewing Part D plan formularies to ensure inclusion of a range of drugs in a broad distribution of therapeutic categories and classes, to satisfy the Medicare Modernization Act requirement that a plan’s categorization system does not substantially discourage enrollment by any group of beneficiaries. Part D plans that use a classification system that is consistent with the USP classification system will satisfy a safe harbor and thus CMS cannot disapprove their formulary classification system. Plans must cover at least two drugs in each distinct category or class.

To review the adequacy of formularies, CMS undertakes a number of formulary checks. In the past, even if a Part D Plan sponsor has not utilized the USP classification system, CMS has relied upon USP’s drug list of Formulary Key Drug Types (FKDTs) to ensure that the formulary provides access to an acceptable range of Part D drugs.

Significant step

Yet the Model Guidelines do not keep current with new drug information and Version 5.0 will be out of date even before it goes into effect on Jan. 1, 2012.

Given the significant gap between USP releases of the guidelines, one questions whether the Model Guidelines serve to protect Medicare beneficiaries’ rights to an adequate formulary. For example, a plan following the USP model guidelines in 2011 would find itself four years behind, thus having a formulary that omits new therapeutic categories and clinically significant medications. Yet such a formulary would meet the Medicare Part D safe harbor for a nondiscriminatory formulary.

CMS explicitly recognizes that prescription drug therapies are constantly evolving and new drug therapies inevitably become available over the course of a single plan year. Therefore, CMS’s policy recognizes that new developments “may require formulary changes during the year to promote high-quality, low cost prescription drug coverage.” Congress also recognized the importance of updating the Model Guidelines and Part D plan formularies to reflect new therapeutic uses for existing drugs and newly approved covered Part D drugs that establish new therapeutic categories or classes. Yet under existing policy, a new drug or a newly approved indication for an existing drug cannot be considered for inclusion in the Model Guidelines until the next three-year revision cycle.

Formulary development and maintenance should be a dynamic process, but the USP Model Guidelines are static. As a benchmark for the adequacy of formularies under Medicare Part D and as a statutory safe harbor, it is time for CMS to consider implementing a process to provide for mid-cycle revisions and updates to the Model Guidelines to reflect new therapeutic uses and newly approved covered Part D drugs.

The authors declare no present conflicts of interest in connection with this article. Ms. Schlosberg did work with two pharmaceutical companies in 2010 regarding presentations to USP, and assisted one of those companies in drafting written comments to USP.

About the authors: Claudia Schlosberg is principal of Schlosberg Consulting and formerly served as director of policy and advocacy for the American Society of Consultant Pharmacists. Richard Stefanacci is an associate professor of health policy at the University of the Sciences, served as a CMS Health Policy Scholar during the introduction of Medicare Part D and is on the MANAGED CARE Editorial Board.
Reach them regarding this article at:

Formulary development should be dynamic, but existing policy says that a drug cannot be considered for the Model Guidelines until the next three-year revision cycle, say authors Claudia Schlosberg, JD (right) and Richard Stefanacci, DO.

Claudia Schlosberg, JD
Richard Stefanacci, DO

Next Generation Anticoagulants May Push Warfarin to the Wayside

Atrial fibrillation patients are often noncompliant with warfarin but newer drugs have better safety and side effect profiles

We are now at a turning point with stroke prevention in patients with atrial fibrillation: Warfarin sodium no longer stands alone.

This means that managed care may be able to vastly reduce the cost of paying for stroke care for the patients currently in rebellion against warfarin who then suffer a stroke. These are patients — up to half of those who have been prescribed the drug — who refuse to take warfarin or take it irregularly for their AF condition and then are hit with a stroke. Warfarin will stand alongside the new drugs, but these other drugs are more patient friendly. A hoped-for outcome is that patients will be more likely to take their medicine and thus prevent strokes. And that means big savings in managed care expenses.

2.3 million

With AF affecting 2.3 million Americans and that number projected to rise to 4 million, we are not talking about minor costs for managed care. And we are not talking only about older people, but many in their 40s, 50s, and early 60s.

New drugs in development

Five alternatives to warfarin
There are five drugs for the prevention of stroke in atrial fibrillation that have been approved or are in phase II or phase III trials. Additional drugs for this indication are in earlier stages of development. Such drugs are also being developed for several other uses, including prevention of venous thromboembolism in general.*
Name Class Route of administration Dosing
Apixaban Factor Xa inhibitor Oral Twice daily
Betrixaban Factor Xa inhibitor Oral Once daily
Dabigatran Direct thrombin inhibitor Oral Twice daily
Edoxaban Factor Xa inhibitor Oral Once daily
Rivaroxaban Factor Xa inhibitor Oral Once daily
YM150 Factor Xa inhibitor Oral Once/twice daily
*Adapted from Piccini JP, Lopes RD, Mahaffey KW. Oral Factor Xa inhibitors for the prevention of stroke in atrial fibrillation. Curr Opin Cardiol (2010; 25: 314).

An array of new drugs are poised to stand beside warfarin for this indication. Dabigatran, developed by Boehringer Ingelheim, recently received FDA approval, and a considerable number of additional oral thrombin inhibitors and factor Xa inhibitors are in both advanced and early clinical trials. “There are so many agents in phase II and III trials that it is likely that not just one but many alternatives are potentially around the corner,” says Jonathan Piccini, MD, MHS, of Duke University Medical Center and an investigator in a major rivaroxaban clinical trial.

The pivotal phase III trial of rivaroxaban, developed by Bayer with support from Johnson & Johnson, was presented at an American Heart Association meeting in November, and an application to the FDA will probably be filed early this year, says Christian Ruff, MD, MPH, of Harvard Medical School. He is an investigator in a major edoxaban clinical trial.

Apixaban, which Bristol-Myers Squibb is developing jointly with Pfizer, is in phase III trials, and findings will probably be presented next summer, Ruff says. Edoxaban, developed by Daiichi Sankyo, also in phase III trials, is likely to have findings presented in 2012.

Betrixaban, which is being developed by Portola and Merck, has a phase III trial in the planning stage. More than a half-dozen additional related drugs are in earlier stages of development.

Nobody is saying that all of the drugs being researched will eventually enter the clinic, but with so many being developed, it would not be surprising if several find their way to doctors’ offices.

Game changer

Dabigatran is a game changer, explains Mintu Turakhia, MD, MAS, of Stanford University and the Veterans Affairs Palo Alto Health Care System. He is senior author of a study of the cost effectiveness of dabigatran recently published in the Annals of Internal Medicine. “It changes the paradigm in stroke prevention for atrial fibrillation in the United States, and that is a very, very good thing.”

Moreover, it is “very relevant to managed care organizations.” The approval of dabigatran “should change the way health care organizations think about health care delivery for patients with atrial fibrillation,” not only a very common but also a very costly condition.

As mentioned, atrial fibrillation now affects more than 2.3 million Americans, and with the age-adjusted prevalence increasing, estimates are that by 2030 this number will grow to encompass 4 million Americans. Annual direct and indirect costs associated with strokes in the United States linked to atrial fibrillation are estimated at $57.9 billion.

Importantly, Turakhia, Piccini, and Shaker A. Mousa, PhD, all observed, when we spoke with them, that once several of these drugs receive approval, the huge market potential and the competitive environment will lead prices lower.

Suboptimal use of warfarin

“The introduction of other oral thrombin inhibitors and factor Xa inhibitors will drive drug costs down over time,” says Mousa, vice provost for research and professor of pharmacology at Albany College of Pharmacy and Health Sciences and author of several review articles on the subject.

Warfarin reduces relative risk of stroke by two thirds, but not if patients do not take it, and between one third and half of patients for whom it is indicated are not taking warfarin, says Piccini. Beyond that, many patients on warfarin remain unable to attain adequate anticoagulation because of factors including drug and dietary interactions, inconvenience of monitoring the international normalized ratio (INR), and the need for frequent dose adjustments. Overcoagulation can also lead to hemorrhage. As Brian F. Gage wrote in a recent New England Journal of Medicine editorial, the real-world effectiveness of warfarin is about 35 percent.

In addition, heart failure or pneumonia sometimes destabilize the INR of patients on warfarin: “It is not uncommon to hospitalize these patients for elevated INR, something that will not be seen with the new drugs, “ Ruff observes.

Multiplicity of new drugs

“These drugs have different characteristics and so will be appropriate for different patients,” Piccini says. As there are multiple drugs now used to treat hypertension or myocardial infarction, so for the first time physicians addressing stroke prevention in atrial fibrillation will be able to choose among relevant drugs, assuming several are eventually approved.

And even right now, it is likely that the availability of dabigatran alone will improve compliance. None of the new agents will affect diet and lifestyle as warfarin does, and so it will be easier for patients to adhere to physician orders, Moussa explains. And if compliance leads to better clinical outcomes in terms of efficacy and safety, then lower costs will follow: More patients will be able to avoid strokes, and expensive stroke therapies will be required less frequently.

Some of the new drugs require once-daily dosing, others twice-daily dosing. They differ in half-life and degree of renal clearance: Only betrixaban is not renally cleared. Researchers are looking at bleeding rates and dyspepsia and other gastrointestinal side effects, Ruff says, noting that all the new drugs differ from warfarin and that it will be some time before we are able to compare them.

For medical procedures that may entail bleeding,“We don’t know yet when patients stop one of these new drugs whether it is safe to give them another anticoagulant” or whether that will be necessary, Ruff says.

Cost of the new drugs

No simple comparison of the costs of warfarin and the new drugs can be made, says Mousa who points out that some costs associated with warfarin can be easily defined (for example, monitoring) but that others are harder to measure (for example, effect of lifestyle/dietary changes).

Meanwhile, larger changes in the U.S. health care landscape may affect warfarin clinics and payments, Piccini notes. “At this point it is impossible to have the entire picture.”

Will individual patients be willing to pay directly for drugs more expensive than warfarin? “I’m not certain the average patient who is taking four or five medications a day will pay for it,” Ruff says.

“The people who can afford the new agents will pay for the convenience of not having to measure INRs along with some of the other benefits. Those who cannot will continue to use warfarin,” Mousa says.

Frederick A. Ehlert, MD, associate clinical professor of medicine at Columbia University Medical Center, is offering dabigitran to all his patients on warfarin, aside from those with renal failure. “Most are switching despite the higher out-of-pocket costs” and he finds there is “a major quality of life impact for patients.” Warfarin costs about $1–$2 per tablet (average wholesale price) depending on the quantity dispensed.

Might it be in the interest of managed care organizations to supplement part of the costs of these drugs as a way to lower overall costs? “When you look at all the associated costs, it may be reasonable to think that lowering the cost of these medications for patients might save health systems a considerable amount of money,” Ruff says.

Who will be given the new drugs?

“Warfarin will be around for a considerable period,” Ruff says, and will be “the dominant player for the future in the United States.” One possibility is that the new drugs will be given primarily to patients not yet on warfarin and those not well controlled on warfarin. “The trial results of dabigatran do not show that it is necessarily better than warfarin” for patients well controlled on that drug.

Mousa agrees that patients noncompliant with warfarin would be good candidates for the new oral drugs, but cautions that “accurate cost-effective comparisons between the different scenarios have not yet been carried out.

“We should keep in mind that warfarin is a very good drug. But it has a narrow therapeutic window and it’s not difficult for patients to slip out of this range, and when that happens, there can be safety problems,” Mousa says.

But dabigitran also “decreases intracerebral hemorrhage rates significantly,” Ruff points out.

“Much safer drug”

For patients compliant with dabigatran, Turakhia says, “The variation in the anticoagulation is much less, and that makes it a much safer drug,” while even patients compliant with warfarin exhibit considerable variation in the quality of anticoagulation depending, for example, on what they ate for lunch.

Should the new drugs be given to patients under age 65 even though the clinical trials have focused on older populations? “The relative benefits and risks for patients younger than 65 may not be very different from those shown in the trials, but it is hard to speculate outside of clinical trials. So, you might do this with caution,” Turakhia says.


Dabigatran, which has received FDA approval, is a “very compelling alternative to warfarin,” Turakhia says. Compared with warfarin, the cost of the 150 mg dose of dabigatran at roughly $8 per day is approximately $12,500 per quality-adjusted life-year (QALY), according to Turakhia’s analysis in the Annals of Internal Medicine. Turakhia describes this level as being “very compelling for health policy” and explains that if other new drugs cost $5 to $6 a day, there could be a net savings associated with their use, if associated expenses are factored in.

“The cost of dabigatran is reasonable, compared with other things we do in medicine,” says Ruff.

The pivotal dabigatran trial published in the New England Journal of Medicine randomized 18,113 patients with atrial fibrillation and risk of stroke to receive either 110 mg or 150 mg dabigatran twice daily (blinded) or warfarin (unblinded), the median duration of follow up being two years. “The 75-mg twice-daily dose now approved by the FDA and was not studied” in this trial, Mousa points out.

The dabigatran trial showed that it carries a slightly higher risk of myocardial infarction than warfarin. “We know warfarin confers some benefit toward the prevention of MI, and that benefit may be attenuated with dabigatran,” Turakhia says. Whether there is a higher risk of MI is a “real concern and we need to see how this drug plays out in the real world.”

The FDA recommends the 75-mg twice-daily dose for persons with poor renal function (creatinine clearance of 15 to 30 mL/min).


In the trial, rate of stroke or systemic embolism was 1.69 percent per year with warfarin, 1.53 percent per year with 110 mg dabigatran (relative risk with dabigatran [RRd] 0.91; 95 percent confidence interval [CI], 0.74–1.11; P < 0.001 for noninferiority) and 1.11 percent per year with 150 mg dabigatran (RRd, 0.66; 95 percent CI, 0.53 to 0.82; P< 0.001 for superiority).

Rates of major bleeding were 3.36 percent per year with warfarin, 2.71 percent per year with 110 mg dabigatran (P=0.003) and 3.11 percent per year with 150 mg dabigatran (P =0.31).

Overall, there was a 60 percent reduction in intracranial bleeds with dabigatran. If bleeding does occur with dabigatran, “the first thing to do is to stop the medication, because the blood levels drop fairly rapidly after you stop the medication,” Mousa says.

Dabigatran has no significant drug-drug or drug-food interactions, whereas there are dozens of drugs that can complicate the creation of a warfarin regimen. The only warning in the FDA label for dabigatran is its contraindication with rifampicin. As to switching patients from warfarin to dabigatran, Moussa explains that “dabigatran becomes therapeutic within 0.5–2 hours of oral administration, so it is pretty immediate.”

Drugs in the pipeline

While dabigatran is a direct thrombin inhibitor, several of the most promising drugs in the pipeline are factor Xa inhibitors. The common branch point for both the extrinsic and intrinsic coagulation pathways, factor Xa inhibitors prevent thrombin formation by interfering with Xa upstream, Piccini explains.

Results from the pivotal double-blind phase III rivaroxaban study randomizing 14,264 patients to the new drug or warfarin were presented at the American Heart Association in Chicago on Nov. 15, 2010 but, of course, the data were neither complete nor peer reviewed.

For many reasons, it looks to be prudent to keep a sharp eye out for these new drugs. Sharp but cautious. “There are a lot of reasons to be excited about dabigatran but caution may be appropriate until there is more experience with them in the real world. I am excited but not ready to switch patients on warfarin until we see how things work in the real world,” Turakhia says.

Surgical advance in treating AF

Catheter ablation is a good option for some patients with atrial fibrillation. “For individual patients, especially highly symptomatic patients who are young and healthy with structurally normal hearts, the therapy is already highly effective and considered the treatment of choice by most physicians. It also offers an important therapy available to treat those highly symptomatic patients who are refractory or intolerant of medications,” says Frederick A. Ehlert, MD, associate clinical professor of medicine at Columbia University Medical Center.

Widely utilized in recent years, it is even more effective than previously, he says, and the risk of major complications is even lower. Advances such as mapping left atrial flutters and assessing rotors have improved outcomes, while monitoring esophageal temperature and ablating in the atrium, rather than at locations used previously, have increased safety.

For some patients, catheter ablation is “a godsend,” he says. “This point cannot be overemphasized.”

Reach the author, Bob Kirsch, at

Patients may not be willing to pay for drugs more expensive than warfarin, says Christian Ruff, MD, MPH, an investigator in an edoxabab trial.

Dabigatran is a game changer that alters the paradigm in stroke prevention, says Mintu Turakhia, MD,of Stanford.

“The people who can afford the new agents will pay for the convenience of not having to measure INRs,” says Shaker A. Mousa.

Bob Kirsch
Legislation & Regulation

Will Therapeutic Interchange Be Put Off Limits by States?

Patient-advocacy groups and some physicians are lobbying legislatures to hobble this common technique to control drug costs

Over the past decade, health plans have designed increasingly sophisticated drug formularies to push their members to the most cost-effective therapies that can treat their ailments. In some cases, new tiers have been added that increase members’ out-of-pocket expenses for pricey biologics. Prices for generic drugs as well as a host of preferred therapies have been reined in. And as branded blockbusters lost their exclusive market status, payers have begun to gain leverage on drug costs by aggressively pushing low-cost therapeutic substitutions.

By pushing up generic drug use, formularies helped save the health care system close to $140 billion in 2009, according to a study by IMS Health. Overall, generics now account for 70 percent to 72 percent of all scripts, says Lisa Zeitel, a senior vice president and AON Hewitt’s national leader for pharmacy consulting. In the next couple of years, with blockbusters like Lipitor losing exclusivity, that rate could easily exceed 80 percent.

To push savings further, formularies increasingly relied on the therapeutic substitution of prescription drugs, using tactics like step therapy. But as therapeutic substitution has become increasingly popular with insurers, it’s been just as effective at agitating doctors and some influential patient advocacy groups. And that is helping to create a fertile landscape for new legislation designed to limit or even stop the practice.

A few weeks ago the Global Healthy Living Foundation, which speaks out on behalf of the chronically ill, released a survey claiming that insurers are now responsible for pushing physicians to switch drugs on up to 70 percent of all prescriptions being handed out. And the advocacy group zeroed in on so-called fail-first brand drug programs, where payers can designate drugs which have to be tried first.

“When patients are switched so the health insurance company can save a few pennies, and then the patient’s chronic condition worsens, not just the patient, but the entire economy suffers,” argues Louis Tharp, the executive director of the foundation.

Prescription switching is an issue that has been resonating with doctors as well. Tharp’s group has been tracking proposed legislation in California, Missouri, and New York that would rein in payers’ switching tactics. And he says that Louisiana legislators have already acted to stop the practice.

In Georgia, meanwhile, the state epilepsy foundation pushed through a law this year that requires prescription labels to alert patients to generic substitutions, as doctors complained loudly about risks. And other state groups are preparing to join the movement as new legislation brews around the country.

In South Carolina, for example, the state medical association recently surveyed its members and found that 97 percent said they had to switch a medication for a patient because of insurance companies’ restrictions — and nearly as many thought that new legislation was needed to better regulate the practice.

Signing off

Analysts are seeing a growing number of step therapy programs, says Zeitel, particularly in drug classes where the insurer’s pharmacy and therapeutics (P&T) committee sees a high level of therapeutic equivalence, such as proton pump inhibitors.

“Some pharmaceutical benefit management programs try to get someone who uses, say, Aciphex, to take another proton pump inhibitor like omeprazole [Prilosec] or Nexium,” she notes. “The emphasis is a generic or formulary brand. Alternative generics are always more cost effective.”

There are some real advantages to these kind of interchange programs, says the Academy of Managed Care Pharmacy, which works with many pharmaceutical benefit managers. When directed by a dedicated team of experts — pharmacists and physicians who understand how to evaluate therapeutic equivalence — substitution programs can save patients money by lowering out-of-pocket costs, help identify medications that can be more convenient to take, and improve compliance rates and outcomes.

P&T experts say that any kind of formulary change is likely to trigger a backlash, so you have to anticipate the reaction and explain clearly what you are doing.

“Implementing a switch from one drug to another within a therapeutic class may be opposed by some on the grounds of convenience or safety as proxies for quality,” writes Marc Mora, MD, a medical director at Group Health Physicians, an integrated physicians group, in the June issue of the American Journal of Pharmacy Benefits. “Committees should respond early to potential arguments against the switch. Including those arguments in communications to patients, physicians, or purchasers also can help align those groups in the change process.”

It’s also important to keep in mind that all payers offer ways to protect patients and listen to doctors’ advice, adds Zeitel.

“In cases where there may be no coverage, there’s always an appeals process,” says Zeitel. That may be a hassle for the member and physicians or their staff, but it does work and has helped mute opposition.

For the plan to get the therapeutic substitution prescribed, though, doctors do have to sign off on the switch first. And that’s when temperatures start to rise.

For the past five years, Hugh Durrence, MD, a family practitioner in Charleston, S.C., has managed to effectively control the blood pressure of one of his hypertensive patients with a branded drug that has worked extremely well. With no warning at all, he says, the patient’s pharmaceutical benefit manager’s formulary changed, excluding coverage of the drug and directing her to get Durrence to choose from five other medications in the same class.

“Just because they’re in the same class doesn’t mean they’re equivalent medications,” says Durrence, angry that a patient of his who has already found a drug that works has to start regular monitoring again to find another one she can afford.

“With another patient,” offers Durrence’s nurse, Jean Moore, “to get the insurance company to pay for the drug, he needed to fail two generics first.” By the time he had finished failing, “he could barely breathe or talk.” And those are just a couple of examples of a growing trend.

It’s a position that the head of the South Carolina Medical Association intends to take up with legislators in his state. The SCMA is “currently prioritizing a number of outstanding issues, therapeutic switching among them, that it intends to aggressively pursue in the next legislative session,” says association CEO Todd Atwater.

Looking for options

Even generic drug substitution — replacing an expensive branded drug with a far less expensive copy containing the same active ingredient — isn’t always safe, say other experts.

One of the most regularly used antiseizure drugs in the United States is Keppra (levetiracetam), says Lawrence Seiden, MD, a neurologist who helped push for the law.

Different standards

“There are about 18 or 20 manufacturers of the generic form of that drug around the world,” says Seiden. “Each manufactures it to different standards, and they don’t have to compare theirs to each other. They just have to present data on how they compare to the original. One [dosage] may run low, another high. Every month a patient’s medication may come from a different manufacturer.”

For epileptics, that variability can lead to trouble, he says.

“Historically, even with the newer generation of antiseizure medications, when patients who are doing well on brand names are switched to generics, there is an increased risk that patients are going to have some problem side effects, recurrent seizures, or both.”

Initially, Seiden adds, the foundation wanted to try for a much tougher law that banned any substitutions. But it couldn’t force insurers to pay for everything that is prescribed. And patients often simply can’t cover the cost alone.

“Our issue is not with the pharmacy,” says the neurologist. “Our issue is with the insurance industry. Many insurers don’t offer adequate reimbursement for the brand-name medicine.”

Any laws that do interfere with a pharmaceutical benefit manager’s ability to steer patients to cheaper drugs probably “would slow down the overall rate of savings,” concedes Zeitel. But the tidal wave of generics cannot be stopped.

Electronic prior authorization

New e-prescribing technology can help, offers Durrence. Insurers could set up electronic prior authorization to make it easier to gain a payer’s acceptance of a needed drug.

“As we get into this new environment of electronic prescribing, we have to leave the medical decisions in the doctors’ hands,” the physician adds. “E-prescribing has to be designed to allow us to promote the highest quality of care, with the right dose to the right patient at the right time. We must preserve the physician-patient relationship.”

Reach John Carroll at

The tidal wave of generics cannot be stopped, says Lisa Zeitel, AON Hewitt’s national leader for pharmacy consulting.

“Just because they’re in the same class doesn’t mean they’re equivalent medications,” says Hugh Durrence, MD, a family practitioner in Charleston, S.C. He is one of many who want to leave well enough alone when a prescribed drug is found to work.

John Carroll