State Medicaid policy encourages use of drug under
fireDespite
federal advisories, state does not restrict Risperdal’s useRichard
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?