Corporate Culture of Denial Results in Preventable Deaths

Fri, 7 Jan 2005

Failure to disclose the hazardous effects of Vioxx and Prozac are evidence of a corporate culture that has run amok. Uncovered company documents – some obtained through litigation, others unearthed by whistleblowers – reveal that the manufacturers knew of the hazardous side effects signaling risk of death. Yet, they embarked on major marketing campaigns, widely advertising dangerous drugs by falsely claiming them to be safe improvements over existing treatments.

The cardiovascular risk was detected in pre-marketing Vioxx tests but was ignored. After the drug was marketed, by 2000 evidence showed that the number of heart attacks in patients prescribed Vioxx had substantially increased – yet, the FDA took no action to protect the public.

A 1988 secret internal Eli Lilly memo shows that in the company’s own controlled clinical trials Prozac had a far higher rate of suicide attempts, hostility, violence, and psychosis than four other commonly used antidepressants in the 1980s and early 1990s: 3.7% attempted suicide — a rate that is more than 12 times that cited for other commonly used antidepressants; 2.3% suffered psychotic depression–more than double the next-highest rate of patients using another antidepressant; and 38% of adult patients who were given Prozac became anxious and agitated (compared to 19% on placebo). See document on CNN website: http://i.cnn.net/cnn/2005/images/01/03/eli.lilly.pdf

Responding to these shocking undisclosed safety hazards (first reported in the British Medical Journal), Lilly issued a statement on Tuesday indicating that "the same records had been given to the Food and Drug Administration and other investigators more than a decade ago." Dr. Alan Breier, Lilly’s vice president and chief medical officer, said: “Our review of the documents shows Lilly has lived up to its commitment of full and important disclosures on this topic.”

The FDA has maintained silence. Congressman Maurice Hinchey has asked FDA’s acting commissioner, Dr. Lester Crawford, to investigate the revelations in the documents to determine what the FDA and Eli Lilly may have known about the relationship between Prozac and increased suicidality; when they knew it; and what they did to protect the public? See: http://www.house.gov/apps/list/press/ny22_hinchey/morenews/010605fdaprozac.html

The Lilly documents show that contrary the company’s denial, Lilly officials knew since at least 1988, that Prozac substantially increased suicidal and violent behavior compared to older antidepressants. Since its approval, the FDA received more adverse drug reports about Prozac than any other drug in history – yet, the agency did nothing to alert the public about the lethal hazards.

See: Hard to Swallow by Thomas Moore, The Washingtonian December 1997 http://www.washingtonian.com/health/hardtoswallow.html

Harvard psychiatrist Dr. Martin Teicher, who first reported the Prozac suicide risk in The American Journal of Psychiatry (1990), told USA Today: "Lives were threatened and Americans treated like ‘guinea pigs’ because Eli Lilly & Co. officials lied 15 years ago in denying there was any evidence the anti-depressant Prozac could cause suicidal behavior."

Dr. David Graham, associate director in the FDA’s Office of Drug Safety, said that Lilly had excluded 76 of 97 cases of reported suicidality from the report submitted to the FDA in 1990. Thus, Dr Graham concluded in a memo dated September 11, 1990 that “because of apparent large-scale underreporting, [Lilly’s] analysis cannot be considered as proving that fluoxetine and violent behavior are unrelated.” http://bmj.bmjjournals.com/cgi/content/full/330/7481/7#FIG1

In 1991, amid public furor over reports of Prozac-induced suicide reports, the FDA convened a panel of experts who exonerated Prozac despite the evidence of safety – the panel’s conflicts of interest were so great that the FDA waived its own conflict of interest rules for 5 of the 9 panelists. However, in August 2003, seven of those panelists told The New York Times that in light of recent revelations about increased suicidality in children, they would reconsider their recommendation. See: https://ahrp.org/infomail/03/08/07.php

For fifteen years, both Lilly and FDA officials vehemently denied a risk existed until the suppressed findings of an FDA report became publicly known. Dr. Andrew Mosholder, an FDA medical officer who analyzed the pediatric test data in 2004, concluded that Prozac and the other SSRI antidepressants posed a twofold increased risk of suicidal behavior for children compared to placebo. But Dr. Mosholder’s report was suppressed by senior FDA officials – it was not made public until AHRP posted it on our website.

Who is telling the truth? What did Eli Lilly and the FDA know about the hazardous effects of Prozac, and what did they do about it?

If Lilly submitted the records to the FDA "more than a decade ago," then FDA officials knew that Prozac posed serioous risks of inducing violent and suicidal behavior: Why did they deny the risks, dismiss the warnings of independent analysts, and fail to analyze the data?

If FDA officials knew the risks described in the 1988 document, given the drug’s minimal proven benefit (if any) in children: Why did the FDA approve the drug for use in children – even as no other regulatory body in the world has?

If Eli Lilly failed to disclose the evidence to the FDA, then the company should be criminally prosecuted to the full extent permitted by law.

AHRP will work to get to the truth.

Representatives of the pharmaceutical industry announced their "commitment to disclose more information about drug studies." Given the long documented record of deceitful advertising and thousands of drug-related deaths due to concealed hazardous drug effects, the American people will not be fooled by such public relations ploys. Non-binding "commitments" that are not legally enforceable will do little to dispel the American public’s distrust of this industry.

See: http://www.nytimes.com/2005/01/07/business/07trials.html?ex=1106111309&ei=1&en=7663d9c1441a3d5c

Contact: Vera Hassner Sharav
212-595-8974

http://www.nytimes.com/2005/01/06/business/06lilly.html?oref=login&pagewanted=print&position=
January 6, 2005
Lilly Says Prozac Documents Contain No New Information
By THE ASSOCIATED PRESS

INDIANAPOLIS, Jan. 5 (AP) – Eli Lilly & Company said Wednesday that internal documents about the safety of its popular antidepressant Prozac – reported in a British medical publication to be long missing – were given years ago to federal regulators and to lawyers suing the company.

The British Medical Journal said last week that it had given United States regulators confidential Lilly documents suggesting a link between Prozac and a heightened risk of suicide attempts and violence. Lilly, which is based in Indianapolis, said it received copies of the documents on Monday from the office of Representative Maurice D. Hinchey, a Democrat from New York, who had been given the records by the publication.

Lilly said in a statement late Tuesday that the same records had been given to the Food and Drug Administration and other investigators more than a decade ago. “Our review of the documents shows Lilly has lived up to its commitment of full and important disclosures on this topic,” Alan Breier, Lilly’s vice president and chief medical officer, said in the statement.

Kamran Abbasi, the medical journal’s acting editor, said Wednesday that the journal had validated its information, and he defended its handling of the documents. A spokeswoman for the F.D.A., Cindy Fitzpatrick, said Wednesday that the agency had received the documents from the British publication but had not yet completed a review of them.

The Jan. 1 issue of the publication reported that the documents, which it said it had received from an anonymous source, had been missing for a decade and that they indicated that Lilly was aware in the 1980’s that the drug could have potentially troubling side effects.

The report said that the documents played a role in a 1994 lawsuit against Lilly on behalf of victims of a workplace shooting in Louisville, Ky. Joseph Wesbecker, who killed eight people and himself in Louisville in 1989, was prescribed Prozac a month before the shootings.

http://www.usatoday.com/news/health/2005-01-05-prozac-usat_x.htm
Psychiatrist: Company hid Prozac, suicide link
By Marilyn Elias, USA TODAY

Lives were threatened and Americans treated like “guinea pigs” because Eli Lilly & Co. officials lied 15 years ago in denying there was any evidence the anti-depressant Prozac could cause suicidal behavior, a Harvard psychiatrist has charged. Harvard psychiatrist Martin Teicher said the American people were “guinea pigs” for Lilly.

The comments by Martin Teicher come as concern mounts over Lilly documents on Prozac described in the British medical journal BMJ last Friday. USA TODAY has obtained a copy of the documents, which were part of a 1994 lawsuit filed against Lilly for victims of a Louisville workplace shooting. The gunman, who killed himself and eight others, had been treated with Prozac.

Teicher, a prominent researcher and clinician, was the first to publish case reports showing an apparent link between Prozac and suicidal behavior in adults. But a few months before his March 1990 report, Teicher said he asked Lilly officials if studies showed such a link.

” ‘Oh no, no, we never heard of such a thing,’ they told me,” Teicher said. But studies from the 1980s showed such dangers, he said, and German drug regulators wouldn’t license the drug when Lilly first applied in 1985, citing “suicidal risk.” The Food and Drug Administration (FDA) approved Prozac in 1987. But when problems started surfacing, the agency held a scientific advisory panel hearing in 1991 and found no evidence of a link to suicide.

Before that hearing, Lilly published studies showing Prozac was safe, Teicher said. “They culled patients from their worldwide trials, they cherry-picked the studies, leaving out the trials showing problems.”

Lilly spokesman Morry Smulevitz said “we are not aware of the conversation that Dr. Teicher refers to with Lilly officials.” He also denied that the company suppressed negative evidence about the drug. “Lilly believes in full and appropriate disclosure of clinical trial data,” Smulevitz said.

The documents summarized in the BMJ article suggest that twice as many patients on Prozac as on a placebo may experience such symptoms as anxiety, agitation and nervousness ­ 38% versus 19%. These symptoms are important because therapists say they can precede suicide or violent acts.

Another document appears to show an FDA official questioning Lilly’s actions in deciding apparent suicide attempts in studies weren’t real attempts or were not due to the antidepressant. Scientists have some discretion in identifying the causes of bad reactions in a study. David Graham, associate director in the FDA’s Office of Drug Safety, reviewed Prozac’s safety record in 1990. “Lilly excluded so many cases of suicidal behavior that I felt a problem couldn’t be ruled out,” he said.

The FDA is still reviewing the BMJ documents, FDA spokeswoman Susan Cruzan said. “But to date we have not seen anything that would lead us to question the conclusions of the (1991 scientific advisory) committee” that there was no tie between the drug and suicide attempts.

Teicher, who considers Prozac valuable, said many of the problems with suicidal behavior were in patients given high doses, and that’s how the drug was used for the first few years in the USA. “American people were guinea pigs for a few years. If we had known the truth, we would have used it more wisely from the start,” Teicher said.

© 2005 The Washington Post Company

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