Evelyn Pringle June 19, 2007
The FDA held a public hearing on June 12 and 13, 2007, to obtain feedback on the FDA's Medication Guide program. Medication Guides contain the FDA-approved patient information for a drug and are handed out by pharmacists to help prevent adverse events.
Ellen Bleecker Liversidge appeared at this hearing as a board member of the Alliance for Human Research Protection to offer feedback for the Medication Guide on Zyprexa, an atypical antipsychotic marketed by Eli Lilly. She began her talk by explaining why the testimony that she had planned to give had to be changed at the last minute.
"I sat down and read over the material provided for this hearing and was all set to speak on content as well as delivery systems," she told the FDA panel. "However, I didn't get very far because, believe it or not, there was no Zyprexa MedGuide."
"Nor were there MedGuides for the other atypical antipsychotics," Ellen said, "all of which have two black box warnings."
"I went back to ask myself why there would be no FDA MedGuide in 2007 for Zyprexa, after all that has happened with this drug, and after all these years," she said, "And that's when I came up with the title of this testimony, 'Too Little, Too Late,'"
Ellen's son, Robert Liversidge III, died of profound hyperglycemia on October 5, 2002, as a result of taking Zyprexa. After finding that there was no MedGuide for Zyprexa, Ellen says she searched the FDA website to see what information was available to patients at that location and found that the black box warning about diabetes, hyperglycemia and death, that she and others had fought so hard to have added to the label 4 years ago, had been watered down. The warning was not listed in a black box, she told the panel, and it was not first on the list.
According to FDA briefing materials for the hearing, a MedGuide is required if a drug has even one of the following characteristics: (1) Patient labeling could help prevent serious adverse effects; (2) It has serious risks (relative to benefits) which patients should be made aware because the information could affect a patient's decisions to use, or continue to use, the drug; or (3) It is important to health and patient adherence to directions for use is crucial to the effectiveness of the drug.
Experts say Zyprexa qualifies for a MedGuide under all 3 categories: (1) The labeling would definitely help prevent serious adverse events; (2) Few patients would be willing to take the drug and risk developing diabetes given that numerous studies have shown Zyprexa to be no more effective than the older class of antipsychotics that do not cause diabetes; and (3) Most patients on Zyprexa would learn that the drug is not FDA approved to treat the condition they have.
In reading the list of adverse events on the FDA website, Ellen says, she found “high blood sugar and diabetes,” mentioned in the number 4 position, even though the wording in the warning in late 2003, specifically included diabetes, hyperglycemia, and death.
"Why was this wording changed?" she asked the panel. "And whose decision was it?"
The current document on the FDA website, Ellen said, is basically useless. Although it did mention that people should get frequent blood glucose monitoring, "There was no indication of how often blood glucose monitoring should take place, nor was there mention of what symptoms of diabetes should be watched for," she noted.
There is no mention that the CATIE study found Zyprexa to have the most lethal side effects out of all the new atypical antipsychotics, Ellen pointed out, or that the American Diabetes Association clearly stated that the risk is the highest with Zyprexa.
There is also no mention, Ellen said, that the use of the drug for treating mania should be brief. When Lilly obtained FDA approval for the sale of Zyprexa in the US in September 1996, the only approved indication was for the treatment of adults with schizophrenia. In 2000, the drug was approved to treat the manic phase of bipolar disorder.
Ellen's son was diagnosed with bipolar disorder years before his death but had always done fine with lithium. However, in 2000, Rob had to apply for Medicaid to help pay his medical expenses and this was his downfall, she says.
During the 1990s, Lilly and the other makers of the new class of atypical antipsychotics, had been successful in corrupting the state Medicaid programs by influencing top officials in state agencies all over the country to write prescribing formularies for doctors that listed the new expensive drugs as the first line of treatment for all patients covered by Medicaid, and that is how Rob ever ended up on Zyprexa.
In 2006, Pennsylvania official Steven Fiorello, former Chief Pharmacist and Head of the state drug formulary committee, was indicted on felony and misdemeanor charges for his conflicts of interests with drug companies and was charged with other ethics violations for accepting "educational grant money" and failing to disclose the payments.
While working as a fraud investigator in the Pennsylvania Office of Inspector General, Bureau of Special Investigations, Allen Jones discovered the off-the-books slush fund account where atypical makers were depositing money under the guise of "educational grants," to influence state officials and policy makers involved in developing the preferred drug list in Pennsylvania. Mr Fiorello was in the position to approve drugs for patients in prisons and 9 state hospitals.
The profits from this scheme were enormous. For instance, Zyprexa was listed for schizophrenia, and Mr Jones' estimates that Pennsylvania has roughly 9,000 schizophrenic patients in state prisons and mental hospitals at any given time.
"And based on the average length of stay," he reports, "an additional 4,000 patients move through the system each year resulting in the potential recruitment of 13,000 customers, worth about $6,000 each per year."
In addition, "when patients leave state institutions with prescriptions for medication," he says, "many of them continue to be supported through Medicaid."
Another former investigator, psychiatrist Dr Stefan Kruszewski, worked in the Pennsylvania Bureau of Program Integrity in the Department of Public Welfare, and says his investigations found serious abuses and over-drugging of patients in state care. One case he reported in 2003 involved four children and one adult who died due to substandard care and the off-label prescribing of atypical antipsychotics.
"The people most vulnerable to the medicating for profit scheme in Pennsylvania," Dr Kruszewski says, "were children in state care or involved in the juvenile justice system, the disabled, and the prison population."
He calls the over-prescribing that took place polypharmacy at its worst. "Nearly all the patients," he explains, "were prescribed a combination of drugs, an antipsychotic and an antiseizure medication."
"But worst of all," he says, "the medical records showed that most of the patients who were receiving the drugs had never been psychotic and had never had a seizure."
"That fact that Medicaid patients are over-medicated to the max," says patient advocate Vince Boehm, "is not debatable."
"According to provider's reports," he reports, "even three antipsychotics, with a witches' brew of other preparations, is not unusual for patients being discharged from state hospitals."
Mr Boehm says the public system has failed these clients and "the taxpayers will be left to subsidize the cleanup of this mess for generations to come."
The ultimate goal in the drugging-for-profit scheme was to keep patients on the drugs for life. For example, Ellen testified that, although Zyprexa was approved only to treat the manic phase of bipolar disorder, which is typically brief, her son "was put on this drug for two years until he fell into a coma and died."
She pointed out that, at the time that he was prescribed Zyprexa in 2000-2002, there was no FDA warning guide so she was completely in the dark about the new drug prescribed to her Rob. Also, she told the panel that the current guide on the FDA website is almost the same as having no guide at all.
"Nothing on this document would have been helpful to me," Ellen said. There is still no description for the symptoms of hyperglycemia that might have saved her son had she known about them the week before he died," she noted.
When Rob suddenly lapsed into a coma and died, Ellen was determined to find out what happened and she subsequently learned that other countries had required warnings about the risk of hyperglycemia, diabetes and death on the label of Zyprexa since the spring of 2002, on the website of the consumer advocacy group, Public Citizen.
During her testimony, Ellen reminded the FDA panel that, back in 2001, before her son was killed, the FDA met with its equivalent agencies around the world, and they all agreed to cooperate with each other particularly on drug safety, and pointed out that this obviously did not happen with the FDA.
"In the spring of 2002," she said, "both Japan and the UK required Lilly to put a warning on Zyprexa for diabetes, hyperglycemia, and death."
"It wasn't as if the FDA didn't already know this," she testified, "because at the end of 2001, Dr. Doriswaimey and an FDA researcher reviewed Medwatch data for Zyprexa and found over two hundred cases of diabetes and 23 deaths."
As a follow-up to Ellen's testimony, a review of the FDA website on June 17, 2007, and the "Patient Information Sheet" on Zyprexa revealed only one warning about the risk of diabetes which states: "High blood sugar and diabetes. Patients with diabetes or who have a higher chance for diabetes should have their blood sugar checked often."
The lack of enforcement action against Lilly over the past 6 years by Bush appointed officials at the FDA is easily explained. Leonard Roy Frank provides a list of many of the reasons in the report titled, "Zyprexa: A Prescription for Diabetes, Disease and Early Death," published in the August 2005 edition of Street Spirit, which states:
"Eli Lilly's ties to the two Bush administrations are a matter of public record. President George H. W. Bush is a former member of Eli Lilly's board of directors. In 2000, Eli Lilly made campaign contributions of $1.6 million, 82 percent of which went to President George W. Bush and other Republicans. In 2001, President Bush appointed Mitch Daniels, a former Eli Lilly vice president, to be White House director of the Office of Management and Budget. In 2002, President Bush appointed Sidney Taurel, Eli Lilly's current chairman and CEO, to the Homeland Security Council."
When the last FDA Commissioner, Lester Crawford, had to get out of dodge and was indicted on charges of conflict of interest for secretly holding stock in companies that were regulated by the FDA, he hopped right from the court house into a job making big bucks off the pharmaceutical industry.
And the revolving door between Lilly and the Bush administration is in full swing today. In May 2007, Lilly issued a press release to proudly announce the hiring of Alex Azar II as a new senior vice president, a guy who was the Deputy Secretary of the US Health and Human Services Department until February 2007.
In the release, Lilly openly bragged about how Mr Azar supervised all operations of the HHS and specifically listed the FDA as an agency under his direction. Although the amount of his salary was not mentioned, if based on a percentage of the profits made from Zyprexa while he controlled the FDA, he should be set for life.
Critics say to look for more top regulatory officials to jump ship before the results are in from the numerous Congressional investigations into the FDA's "cozy" relationship with the pharmaceutical industry and the mishandling of drug safety issues.
At the moment, Congress is investigating Lilly for ripping off Medicaid and Medicare with the illegal marketing of Zyprexa and the criminal investigations of Lilly by US attorneys in various states are too numerous to keep track of.
As far as litigation against Lilly related to the illegal marketing of Zyprexa, so far, 10 states have filed Medicaid Fraud lawsuits, 4 class actions were filed by shareholders over a 9-day period in April, and Lilly has agreed to pay more than $1 billion in out-of-court settlements with over 28,000 private Zyprexa victims.
There are additional cases filed by insurance companies and employer unions that provide prescription drug coverage to private payers, and citizens and entities in other countries also have also filed lawsuits against Lilly.
In every case filed, the allegations include that Lilly marketed Zyprexa for unapproved uses and concealed the serious health risks associated with the drug, and most prominently, the complaints list the adverse effects of abnormal blood sugar levels, extreme weight gain and diabetes, according to Ely Lilly's April 16, 2007 SEC Form 8-K filing for the first quarter of 2007.
Considering everything revealed about Zyprexa in the filings of all of this litigation, medical professionals and patient advocacy groups are infuriated over the fact that Lilly is still profiting from the drug. In the first quarter of 2007, sales were up 11% in the US from last year, and Zyprexa earned Lilly more than $1.1 billion, according to the company's April 16, 2007 SEC filing.
However, critics say they are even more outraged that the sales of Lilly’s top selling diabetes drug, Humalog, are up 11% over last year.
"The fact that this drug continues to be marketed," Mr Frank says, "that the media has barely covered the story, that there have been no criminal charges against the responsible parties and that there has been no outcry from the psychiatric profession or the public, have only compounded the crime."
"Lilly's introduction of Zyprexa and the FDA's complicity," he states, "have led to one of the greatest crimes in medical history in terms of the number of people harmed, the damage inflicted, and the grossness of fraud in promoting and advertising the drug."