Sunday, May 17, 2009

State Medicaid policy encourages use of drug under fire

5/5/2009 11:04:00 AM Email this articlePrint this article 
State Medicaid policy encourages use of drug under fire
Despite federal advisories, state does not restrict Risperdal’s use
Richard Moore
Investigative Reporter

A Lakeland Times investigation

The second in a series

As a thick thunderhead of concern over so-called atypical antipsychotic drugs continues to rumble across the country, the state of Wisconsin is keeping some of the medicines on its Medicaid Preferred Drug List, including the most controversial one, risperidone, thereby encouraging through official policy its widespread use in nursing homes and by doctors.

In contrast, a number of states, including South Carolina and Texas, have filed lawsuits against the drug's brand-name manufacturer, Janssen Pharmaceutica, calling its product, Risperdal, among other things, inherently dangerous and hazardous to human health and seeking the return of millions of dollars in Medicaid reimbursements paid to the company.

Not in Wisconsin, however, where Risperdal and, as of last year, its generic formulation remain popular with the medical establishment, and the preferred drug designation means it can be dispensed without medically necessary prior authorization (though since November using Risperdal rather than the generic product requires a brand-necessary prior authorization).

But as the drug flows as freely as ever to patients often unaware of the threats, an equally steady stream of studies continues to connect Risperdal and other so-called atypicals to a broad array of health risks and side effects.

The federal Food & Drug Administration issued a warning in 2003 after clinical trials linked the drug to a significant increase in the risk of stroke and diabetes. In 2005, FDA whistleblower Dr. David Graham estimated that off-label use of atypicals could cause as many as 62,000 excess deaths a year.

More recent studies have underscored the high risk of mortality in all of the atypicals.

For example, patients ages 30 to 74 who took atypical antipsychotics such as Risperdal, Seroquel, Zyprexa and Clozaril had a significantly greater chance of sudden death from cardiac arrhythmias and other cardiac causes than patients who did not take them, according to a report released in January by the federal Department of Health & Human Services' Agency for Healthcare Research and Quality.

The higher the dose, the greater the risk of death, the study found.

What's more, the state approved Risperdal as a preferred drug without any diagnostic restrictions almost a full year after the FDA issued a black-box warning about giving Risperdal and other atypicals to the elderly. The FDA acted after 15 out of 17 clinical trials showed morbidity rates rising 70 percent among elderly patients with dementia after being treated with the drugs.

In the Badger State, one northern Wisconsin family says their elderly father died last year after being put on Risperdal at Taylor Park Nursing Home in Rhinelander, and The Lakeland Times has confirmed other cases where elderly patients treated for dementia or aggression have suffered adverse reactions.

Many of those affected are pointing fingers at doctors and nursing homes, but, whether or not that blame is justified, the rise of Risperdal is a story that starts with the state itself - and in the obscure committees that recommend approval of drugs for preferred use.

The preferred drug list

The state initially adopted a preferred drug list in 2004, after Gov. Jim Doyle pressed for the measure in his first budget address. Doyle said the program would save Wisconsin taxpayers $15 million a year.

It works like this: The state selects brand-name prescription drugs to include on the list, which means they do not require "prior authorization" before Medicaid will reimburse payments for them. Non-preferred drugs in the same classes do require prior sanction, though a doctor can seek the use of a non-preferred drug if the patient meets certain medical criteria.

For those considered for a spot on the preferred list, the state tries to negotiate a deal with the pharmaceutical companies in which a certain percentage of the costs are rebated to the state.

For example, Wisconsin paid $10 million in atypical antipsychotic reimbursements in the first quarter of 2006, though, after rebates, the final cost was about $7.5 million. That's a pace of about $30 million a year just for atypicals, but it also represents a savings of about $10 million over the price had the rebates not existed.

"I am committed to ensuring that people get the prescription drugs they need, while taxpayers are protected by smart buying at better prices," Doyle said in announcing the preferred drug list program. "These new measures will result in the largest drug discounts and lowest drug prices ever received by the state for the Medicaid, BadgerCare, and SeniorCare programs."

At the time, a Department of Health and Family Services division administrator, Mark Moody, said the preferred drug list was based on the "therapeutic significance and cost effectiveness of each drug."

To establish drugs on the list, he said, the state's Medicaid Prior Authorization Advisory Committee reviewed the most current research and clinical information available, as well as drug price information submitted by manufacturers.

But what were the real criteria the prior authorization advisory committee - a group of physicians, pharmacists, and advocates, according to the Doyle administration - used in making its decision?

To answer that question requires a look at the committee as well as the minutes of the meeting during which the decision about atypicals was made.

A fateful day

Risperdal's run in the sun in Wisconsin began on March 29, 2006, when the state's Medicaid prior authorization advisory committee convened to consider the class of drugs known as "atypical antipsychotics."

The committee's members were Tom Frazier, the executive director of the Coalition on Aging; Nancy Phythyon, the president of the Wisconsin chapter of the National Alliance on Mental Illness (NAMI); Michael Witkovsky, a child psychiatrist; Steve Mailke, a 25-year professional in the pharmaceutical healthcare industry and a vice president of Trivantage Pharmacy Strategies, a pharmacy benefit consulting and auditing firm; Alicia Walker; and Rosanne Barber.

In all 14 people offered "public" testimony that day before the committee, according to the meeting summary; not one opposed the inclusion of the atypicals on a preferred drug list nor did anybody request diagnostic limitations. Indeed, most cautioned the panel not to restrict physicians' prescribing options but to give doctors wide discretion to choose among the various brands.

There was Carol Mixdorf, a parent of a consumer, who said prescribing flexibility had given her the ability to obtain a variety of drugs for a family member - drugs that had led to less frequent hospitalizations and allowed the family member to work.

Jennifer Lowenberg, of NAMI, also favored no prescribing limitations, as did Dr. Luis Vazquez, a Milwaukee psychiatrist who said restricted access would increase emergency room and other physician-related costs.

Six industry representatives touted their own brands for the preferred drug list, while Gary Yeast of the Wisconsin Coalition for Advocacy, Dr. Burr Eichelman of UW Hospital and Jerry Halverson of the Wisconsin Psychiatric Association also testified in favor of including atypicals without prescribing limitations.

Without question, speakers with affiliate connections or personal ties to the pharmaceutical industry dominated the session. The clamor for PDL inclusion of the drugs by industry representatives was obvious, but some of the "advocacy group" testimony cannot be accepted at face value, either, given long-standing and recently renewed questions about pharmaceutical industry influence within that sphere.

Take NAMI, for instance, which has a history of association with such pharmaceutical giants as Ely Lilly, which manufactures Zyprexa. According to a report in Mother Jones Magazine, pharmaceutical companies donated $11.7 million to the group between 1996 and 1999 alone.

A 2001 NAMI publication, "Access to Effective Medications," promoted the atypicals, and the organization has conducted a decade-long lobbying effort at the state level for the drugs. The group also pushes another program - TeenScreen - which critics blame for an exponential increase in antipsychotic prescriptions for teenagers.

More recently, NAMI's 2007 annual report lists the makers and developers of major antipsychotics - Janssen; GlaxoSmithKline Plc; Eli Lilly - among the group's corporate partners, along with the Washington-based trade group Pharmaceutical Research and Manufacturers of America.

Grassley launches probe

Just three weeks ago, Sen. Charles Grassley (R-Iowa) broadened his probes of pharmaceutical influence in health care policymaking by homing in on the finances of non-profits, especially NAMI. Grassley acted after a piece in the Journal of the American Medical Association rekindled concerns about the cozy relationships between advocacy groups and industry.

On April 6, Grassley sent a letter to NAMI asking the organization to disclose its industry funding.

"For the last three years, the (Senate Finance) Committee has been investigating various aspects of the pharmaceutical industry, including consulting arrangements and industry funding for Continuing Medical Education (CME)," Grassley wrote. "... I have come to understand that money from the pharmaceutical industry shapes the practices of non-profit organizations which purport to be independent in their viewpoints and actions. Specifically, it is alleged that pharmaceutical companies give money to non-profits in an attempt to garner favor in ways that increase sales of their products."

Grassley has asked NAMI to document any transfer of value from a pharmaceutical company, including grants, donations, and sponsorship for meetings or programs from January 2005 to the present.

The American Psychiatric Association has also come under scrutiny from Grassley and his committee for its ties to the industry. The senator asked for an accounting of its finances last year.

In 2006, according to the New York Times, the drug industry accounted for about 30 percent of the association's $62.5 million in financing, with 50 percent coming from advertisements in psychiatric journals and exhibits at its annual meeting, and the other half to sponsor fellowships, conferences and industry symposiums.

In March, the association said it would no longer accept industry support for symposiums and meals.

Consulting independence?

If the public at the prior authorization advisory committee's March 2006 meeting was largely a subset of what might be called the pharmaceutical industry public, the consultant-driven reviews following the testimony did little to cast doubt on what committee members had just heard.

Following a closed session, the committee entertained Dr. Valerie Taylor from Provider Synergies - which has signed a consulting contract to manage Wisconsin's PDL and to provide rebate contracting services - who presented a therapeutic class review of atypicals, and Dr. Mike Mergener from APS Healthcare, who provided summary conclusions from the Drug Effectiveness Review Project (DERP).

Neither addressed any concerns with the drugs, at least according to the meeting summary, but rather restated pharmaceutical company arguments.

"The side effect profiles differ from conventional antipsychotics by producing low EPS (movement disorders) and they also are effective in decreasing negative symptoms associated with schizophrenia," the minutes summarize Taylor's presentation.

Taylor did not mention - or the minutes do not reflect it - that several studies had, by March 2006, challenged the claim that atypicals have fewer side effects and were more effective than the older antipsychotics.

For example, a 2000 Oxford University analysis of 52 studies published in the British Medical Journal found no difference in effectiveness between the newer and older drugs, while a 2003 German review in The Lancet found only Clozaril to have fewer side effects than the older medications.

A 2003 U.S. Veterans Affairs study of 309 patients with schizophrenia or schizoaffective disorder found "no significant differences" between the two groups in terms of schizophrenia symptoms, dropout rates, quality of life, or EPS.

Also lacking in the official record of Taylor's presentation was any mention of the FDA's 2003 warnings about an increased risk of diabetes and stroke and its 2005 black-box warning about increased risks of death among the elderly, which had been issued only 11 months before.

Taylor did say that, in comparing the atypicals among themselves, the drugs showed a similar efficacy, with Risperdal causing the most EPS.

Mergener reviewed the so-called DERP report.

The Drug Effectiveness Research Project, or DERP, is part of the Oregon Evidence-based Practice Center at the Oregon Health and Science University. It was established in 1997 as a collaboration of public and private organizations, now including 18 states, that have joined together to provide systematic evidence-based reviews of the comparative effectiveness and safety of drugs and then to use the findings to make public policy decisions, such as which drugs to include on PDLs.

The pharmaceutical industry has never been crazy about the DERP program, but, on the other side of the unsympathetic coin, critics have said the findings drive patients to certain drugs, and that many of the findings are too narrowly drawn.

That may or may not be. Consumer Reports used DERP data to draw its own conclusions, and it did report that the older antipsychotics were as safe and effective as the newer atypicals. Still, that didn't stop the group from naming Risperdal one of its Best Buy drugs, and the official record of Mergener's 2006 presentation does not cite any problems that might be contained within the DERP data.

"... the report found that in head-to-head studies, different drugs in the class have different superiorities, in efficacy depending on the study," the minutes cite Mergener as reporting. "Overall, no agent demonstrated consistent benefit over any other drug. There are a wide variety of differences in the side-effect profiles of the drugs. In summary, there are no clear-cut first line agents in indications, efficacy or side-effect profiles."

That said, the advisory committee proceeded to a vote, a unanimous approval of Risperdal and other atypicals for the PDL list, without diagnostic restrictions. Only Zyprexa and Symbyax were left off.

A state mental health advisory committee reviewed the recommendation the following month; the DHFS secretary then approved it.

To be sure, the official record of the March 29 meeting does not reflect discussions about atypicals that might have occurred in prior meetings, and it is itself only a summary of that meeting, but at the committee's subsequent August meeting no one challenged its accuracy and voted unanimously to approve the summary - a record that tilted heavily toward broad use of the drugs.

Then, too, the vote to put certain atypicals on the list itself ratified the official record, but, given the limited testimony and omitted hazards, was the decision based on what Moody had said would be "the therapeutic significance" of the drugs or on something else? It was a question a member of the mental health advisory group would ask the following month.

During that April 12 meeting, Moody acknowledged the limited testimony, according to the meeting summary: "He indicated that they reserved time for consumers to testify but had limited consumer testimony due to a variety of factors."

The variety of factors was not defined.

Then, at one point, committee member Harold Harsch "questioned the logic behind not including Symbyax and Zyprexa," the summary states. "Mr. Moody responded that he could not speak for the committee members but indicated the discussion focused on side effects and cost."

Mental Health Advisory Committee member Barry Blackwell commented that both of the recommended non-preferred drugs were from the same manufacturer, which did not offer supplemental rebates. He questioned whether the decision was based on science or finances.

According to the summary, Moody responded that the committee was advised to consider the clinical evidence first. All in all, though, the discussion was confined to a dialogue about which atypicals should be on the lists, not about the efficacy of whether any should be on the list.

The die was cast.

To live or let die?

Certainly Risperdal and other atypicals had been prescribed by doctors and used in nursing homes long before that March 2006 vote, but the decision that day set the stage for the drugs' continued and, indeed, even more widespread, dispensation.

As one mental health advisory group member said in the April meeting, if a drug is not on the PDL, a doctor isn't likely going to use it.

The decision may have led to other serious ramifications.

For instance, the state did not update its medical consent form to include the federal black-box warning until this past month, four years after its issuance. That form is used by nursing homes to get treatment consent from patients and families.

Meanwhile, until very recently, studies have shown a marked increase in the use of Risperdal and other atypicals in nursing homes, particularly to elderly dementia patients. About 30 percent of all nursing home residents receive antipsychotic drugs, according to the U.S. Centers for Medicare & Medicaid Services, and about 20 percent of residents who do not have a psychosis diagnosis are on the drugs, CMS reports.

Citations for violations of drug-misuse rules have increased by nearly 40 percent since 2004, CMS states, though many facilities are reducing their use of antipsychotic drugs and more carefully monitoring residents who use them.

The numbers vary greatly from state to state, and, with increasing criticism directed at the drugs, many facilities are using them only as a last resort.

That does not appear to be the case in Wisconsin.

Back in 2006, a member of the state's mental health advisory committee put his finger on the problem.

For 20 years, according to the minutes, Ted Collins said he had been looking at nursing home populations. Twenty-five years earlier, he stated, there was an overuse of traditional antipsychotics in nursing homes, which regulations had dramatically decreased. Now, though, he said, the introduction of atypicals had become no less problematic.

As a preferred drug in the state of Wisconsin, in 2009, it has likely become even more problematic, and, many say, more deadly than ever.

Next: A risperidone death at Taylor Park Nursing Home?

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