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A lawsuit filed against Pfizer Inc. two years ago and just unsealed last month calls into question the safety of the company's popular antipsychotic drug Geodon as well as the reputation of some of the researchers who worked on its clinical trials.
The lawsuit, filed by Dr. Stefan Kruszewski of Harrisburg, Pa., alleges that three of the researchers who helped conduct Geodon clinical trials - Dr. Richard Borison, Dr. Bruce Diamond and Dr. Louis Fabre - have been sanctioned by regulatory authorities. Borison and Diamond were debarred by the U.S. Food and Drug Administration and received prison time, according to the suit, and Fabre earned sanctions in Texas for research misconduct.
"Pfizer's reliance on clinical researchers with a known history of professional misconduct" - which news reports indicate go back at least as far as a 1997 indictment of Borison and Diamond and included the FDA's 2005 shutdown of Fabre's clinical-testing facility - "demonstrates the lengths to which the company is willing to go to facilitate its 'positive' clinical trials' reporting," according to the suit.
Pfizer isn't the only company that used Borison and Diamond to do clinical studies of schizophrenia patients. A 1998 Boston Globe article cited the pair as a "favorite" of such other drug firms as Eli Lilly & Co., Janssen Pharmaceutica, AstraZeneca Pharmaceuticals and Novartis.
Questions about drug-research procedures have been a long-standing bone of contention, with some critics charging that statistics can be manipulated, especially now that much of the research trials are funded and controlled by pharmaceutical companies with an inherent interest in having their compounds brought to market.
Pfizer, in a statement, broadly denied allegations in the Kruszewski lawsuit. A Pfizer spokeswoman added that "a rigorous internal system is used for monitoring the safety of patients in clinical trials. In addition, independent data monitoring boards are often used during later stages of development."
The FDA would not address whether the agency is reviewing Geodon data based on allegations contained in the lawsuit. It also said it could not comment on whether the FDA would be investigating any of the clinical researchers associated with Geodon's approval, some of whose names are redacted in official documents supplied by the agency.
But in a statement, the FDA said it "does go back and relook at data if we become aware of possibly fraudulent data."
"Regarding Geodon specifically, the FDA feels that we have accurate information and we feel the drug label accurately reflects the risks and benefits of this drug," said agency spokeswoman Sandy Walsh in a statement.
The FDA branded as false an allegation in the lawsuit that the agency approved Geodon's marketing over strong objection from its staff.
The FDA said it has no control over the practice of medicine and how doctors prescribe drugs. All it can do, the agency said, is regulate off-label promotion of drugs by pharmaceutical companies.
Kruszewski's suit questioning Geodon's approval was unsealed at about the same time as another legal action in which former Pfizer sales representative Mark R. Westlock accused the company of using the National Alliance on Mental Illness as a "Trojan horse" to push off-label use of the drug.
Doctors are allowed to prescribe drugs off-label for conditions not specifically approved by the FDA with the understanding that individuals may be helped by a drug that doesn't prove particularly effective in a large population. But companies are not allowed to promote off-label uses as if they were clinically proven treatments.
The Kruszewski lawsuit is part of a series of whistleblower actions that led to an announced $2.3 billion in penalties against Pfizer this month for illegal marketing tactics related to several of its best-selling drugs.
The suit was initially sealed, but became a public document when the U.S. District Court for the Eastern District of Pennsylvania released it after Pfizer agreed last month to settle various illegal-marketing cases throughout the country. The cases included a $1 billion civil penalty as well as $1.2 billion for what turned out to be the largest criminal fine in U.S. history.
But while money seemed to be at the heart of many of the illegal-marketing schemes that Pfizer allegedly engaged in, Kruszewski's suit extends concerns about the company into the critical area of clinical science - the process by which authorities determine the safety and effectiveness of a new drug. The suit claims that Pfizer presented misleading data to the FDA before receiving approval for Geodon and indicates that the antipsychotic medication may be riskier than the company has been willing to admit.
To bolster his points, Kruszewski, identified as a board-certified expert in psychopharmacology, alleges in the suit that Pfizer misled an FDA advisory committee about the frequency of adverse reactions to Geodon and gave incorrect information to authorities about possible "favorable effects" of the drug on heart-disease risk factors such as cholesterol levels.
In fact, Kruszewski said in the suit, Geodon has been tied to prolonged heartbeats. The lawsuit also cites what he calls "undisclosed side effects" of Geodon for some people, including substantial weight gain, restlessness and increased risk of infection.
This wouldn't be the first time that research associated with Pfizer has been tied to skewed data. Earlier this year, Dr. Scott Reuben, a Baystate Medical Center researcher in Springfield, Mass., and a former member of Pfizer's speakers' bureau, was accused of perpetrating one of the largest research frauds in U.S. medical history for apparently making up data to support the preconceived notion that a combination of two of the company's drugs, Lyrica and Celebrex, helps with postoperative pain.
Geodon, known generically as ziprasidone hydrochloride, was discovered and developed at Pfizer's campuses in Groton and New London. The FDA approved its use in 2001 after denying an application to market the drug under a different name three years previously.
The so-called non-approvable letter cited concerns over safety data, particularly a "potentially fatal" heart problem tied to Geodon. Later studies submitted by Pfizer, however, showed serious side-effects from using the medicine fell in a range similar to other atypical antipsychotic medications.
But an analysis of statistics on deaths of patients exposed to experimental doses of Geodon showed a "mortality rate ... higher than the rates observed for other recently reviewed antipsychotic medications," and that "cardiovascular related deaths were more commonly observed in ziprasidone treated individuals compared to patients receiving placebo or active (similar) medications," according to an FDA report. But the death rate, which tends to be higher for schizophrenics than for other populations, was an improvement over those given a placebo, the report stated.
Though the FDA eventually approved the use of Geodon, it did so under the condition that labeling identify only three relatively uncommon conditions for which it should be prescribed.
According to the suit, Pfizer's sales team immediately went to work in an effort to expand Geodon's market by promoting off-label uses of the drug, including for pediatric patients with autism-spectrum disorders and elderly patients with dementia and depression.
In fact, the suit states that Pfizer's promotion of off-label uses for its drug convinced at least one psychiatric unit in Pennsylvania to issue a standing order to administer Geodon if a dose of the antipsychotic drug Depakote was refused. A nursing home, according to the suit, routinely administered Geodon off-label to treat nighttime disruptiveness and agitation.
Kruszewski, who calls himself "an eyewitness to Geodon off-label promotional marketing," said in the suit that Pfizer hired pediatric psychiatrists to give lectures promoting the drug.
"Pfizer had a large number of child psychiatrists routinely paid substantial honorariums to give purportedly 'educational' lectures about Geodon," the suit states.
Kruszewski received $29 million as his share of more than $100 million received by Pfizer whistleblowers in the settlement announced earlier this month.