Intimidation, Politics and Drug Industry Cripple U.S. Medicine – FDA Permits Dr. David Graham to publish Vioxx Report

Intimidation, Politics and Drug Industry Cripple U.S. Medicine – FDA Permits Dr. David Graham to publish Vioxx Report

Wed, 5 Jan 2005

FDA officials could not maintain their iron grip in an effort to suppress evidence of far reaching lethal effects of Vioxx when their actions were in full public view. FDA officials were forced to lift the roadblocks they had put in Dr. David Graham’s way. They gave him approval to publish his findings, enabling independent scientists to critically examine those findings and validate or refute them – in accordance with the scientific method.

The collision between Dr. Graham and his bosses at the FDA provides a ringside view of a public agency derailed from its public mission– which is to protect the public from unsafe drugs and medical devices. Instead of using the agency’s authority to enforce safety standards, FDA officials misuse that authority to bully and intimidate the agency’s own senior medical officers whose analyses of the evidence refutes drug manufacturers’ claims about their drugs’ safety.

FDA officials actively impeded the efforts of the agency’s own medical experts when they sought to inform the public about hazardous drug effects – as is their professional and public responsibility. Among the medical officers whose scientific findings were suppressed, was Dr. Andrew Mosholder. His February 2004 report about SSRI-induced suicidal behavior in children was suppressed until AHRP posted it on our website.

When a consciencious scientist is malligned for his efforts to protect the public from unsafe drugs; when a legitimate scientific analysis that has been accepted for publication by the world’s leading scientific journal – The Lancet–is viewed by FDA officials as posing a threat to the agency; we have a major credibility crisis. How can the FDA claim its decisions are grounded in “science-based evidence” if the agency suppresses the disclosure of scientific findings?

This collision between FDA scientists in the safety division who seek to protect the public from unsafe drugs – as is their professional and public responsibility–and FDA management which is alligned with the pharamaceutical industry, is evidence of a major rupture. FDA officials who govern the agency have shown a willingness to sacrifice safety – thereby incurring preventable human casualties – in order to protect drug sales. This intolerable misdirection requires legislative action to put the agency back on track.

As Dr. Graham states (below) “You have an agency in denial — the FDA still maintains it made no mistake in the approval or regulation of Vioxx.” Indeed, on Novermber 8, Dr. Sandra Kewder, deputy director of F.D.A.’s office of new drugs, defended the benefits of Vioxx on National Public Television – after Merck withdrew the drug–claiming that the deaths linked to Vioxx are “not real deaths.” [1]

When the public learned about concealed lethal drug side effects and the consequent preventable loss of lives, they lost trust in the agency’s seal of approval. When the public realized that profit margins escalated as did the body count from adverse drug effects, public opinion of the pharmaceutical industry sank to the level of the tobacco industry. The public is tuned in to independent sources of information: independent analysts, investigative reporters and inside whistleblowers have uncovered a mountain of corroborating evidence.

In the case of SSRI antidepressants:

Dr. Graham notes that the FDA’s proposed new label for SSRI antidepressants cites a “suicidality” rate of one to two percent, but a senior FDA official acknowledged in September that that number was based upon drug trials that “failed to capture most of the reactions of suicidality.” But, he points out, the finding in an alternative trial – Treatment for Adolescents with Depression Study (TADS)–“the actual rate was somewhere around seven or eight percent,” which, as he says, is an incredibly substantive difference from the proposed FDA numbers in the warning label.

Indeed, in the TADS experiment, there were 7 suicide attempts – 6 in the Prozac group, one in the placebo group. The rate for adverse events involving deliberate harm (to self or others) in children in the Prozac group was 12%, additionally suicide-related events in the Prozac group reached 8.26%. More than twice the rate in the placebo group: 5.36% and 3.57% respectively. [2]

Evidence of the hazards of Prozac and the other SSRI antidepressants that had been hidden for decades – or deliberately miscoded–is coming to light: the hazards include severe withdrawal symptoms – which is evidence of drug dependency; mania; violence; suicide; and cardiac abnormalities. Additionally, children prescribed an SSRI are at risk of decreased growth and an unusual high incidence of conversion from drug-induced mania to manic-depression (bipolar)–previously a rare diagnosis in children.

All of these hazards continue to be downplayed by the FDA and leading psychopharmacologists who have considerable (mostly undisclosed) financial stakes in the pharmaceutical industry. Most of the “experts” usually cited in the press have tested the drugs in clinical trials but failed to disclose in published reports the negative findings, hazardous – even lethal – adverse events that occurred in the trials. Company officials and psychiatrists from prestigious medical institutions–who are paid consultants or recipients of grants from drug manufacturers – have tainted the scientific literature. They have misled prescribing physicians with reassuring, but unsupportable claims that the drugs were “safe and effective” when the drugs have failed to demonstrate a clinically significant benefit, but posed clinically significant risks of harm:

When questioned by about the TADS findings by Psychiatric News, Dr. Graham Emslie, one of the lead investigators of the trial acknowledged: “Patients receiving fluoxetine alone had the highest risk…of experiencing a harm-related event, compared with those receiving placebo.” [3]

1. See: NewsHour DRUG FAILURE, Public Broadcasting Station. November 18, 2004.
http://www.pbs.org/newshour/bb/health/july-dec04/vioxx_11-18.html

2. Fluoxetine, Cognitive-Behavioral Therapy,and Their Combination for Adolescents With Depression Treatment for Adolescents With Depression Study (TADS) Randomized Controlled Trial, JAMA, August 18, 2004 – Vol 292, 807-820, Table 3.

3. Jim Rosack. Drug/CBT Combo Effective In Treating Depressed Youth, Psychiatric News September 3, 2004, Volume 39 Number 17 © 2004 American Psychiatric Association. Online at: http://pn.psychiatryonline.org/cgi/content/full/39/17/1

Contact: Vera Hassner Sharav
212-595-8974

THE LOS ANGELES TIMES
January 4, 2005
FDA Allows Scientist to Publish Data on Vioxx
From Times Wire Reports

The Food and Drug Administration has given a whistle-blower scientist permission to publish data indicating that as many as 139,000 people had heart attacks that may be linked to Vioxx, the scientist’s lawyer said.

Dr. David Graham, who works in the FDA’s Office of Drug Safety, testified in November before a Senate panel that the FDA fumbled in its handling of safety concerns around Vioxx and had mishandled concerns about five other widely used drugs. The FDA denies the allegations.

http://www.commondreams.org/headlines04/1231-02.htm
Published on Friday, December 31, 2004 by the Inter Press Service
Intimidation, Politics and Drug Industry Cripple U.S. Medicine
by Ritt Goldstein

STOCKHOLM – While the U.S. Food and Drug Administration (FDA) is supposed to safeguard the nation’s medical products, drawing upon the substantive expertise of its drug scientists in vigilant dedication to the public’s health, that is not the case today.

Documentation, interviews and recent drug debacles depict a brutally different reality, with the Vioxx scandal alone estimated to have resulted in 30,000-55,000 U.S. deaths.

“You have an agency in denial — the FDA still maintains it made no mistake in the approval or regulation of Vioxx,” says the agency’s associate safety director, Dr David J Graham.

Vioxx was voluntary withdrawn by its manufacturer, Merck and Co, on Sep. 30, 2004 due to substantively increased risk of heart attack and stroke. Since then, questions have been raised regarding similar problems in other pain medications like Celebrex and Aleve.

Graham, who provided the figures on the Vioxx deaths, also told IPS that — despite the recent linkage between some antidepressants and suicide — the FDA is in the process of “misleading the public in their (antidepressant) labeling … taking care of business rather than patient safety.”

Graham, whose November testimony before the U.S. Senate Finance Committee rocked the FDA’s leadership, warned that while the agency’s proposed new label for the class of antidepressants known as SSRIs cites a “suicidality” rate of one-two percent, a senior FDA official acknowledged in September that number was based upon drug trials that “failed to capture most of the reactions of suicidality.”

A 20-year FDA veteran, Graham then noted that an alternative trial found “the actual rate was somewhere around seven or eight percent,” an incredibly substantive difference from the proposed FDA numbers.

Investigation reveals that dangers of drugs are being deliberately downplayed, and the public misled.

Notably, a March 2003 report by the U.S. Department of Health and Human Services Inspector General (DHHS-IG), Janet Rehnquist, found that just 12 percent of FDA scientists were completely confident that “labeling decisions adequately address key safety concerns.”

In his most recent congressional testimony on Nov. 18, Graham named five drugs as candidates for market withdrawal: Accutane, an acne treatment; Bextra, the pain medication; Crestor, which lowers cholesterol; Meridia, a weight reduction drug; and Serevent, an asthma medication.

All of the preceding drugs’ manufacturers were reported declaring their medications safe, paralleling similar pronouncements made by Merck and Company prior to its withdrawal of Vioxx.

At the same time, the Senate Finance Committee chairman, Iowa republican Charles Grassley, expressed his belief the FDA was “too cozy” with the drug industry.

Graham urged Congress to pursue legislation separating the FDA offices that address drug safety from the drug review and approval structure, arguing that creating an independent body to review drug problems would avoid the need to seek action on problem medications from the very individuals who had approved them, which is now what happens.

Both the FDA and the National Institutes of Health (NIH) have come under increasingly strong criticism for alleged distortion of research, their “cozy” relationship with the drug industry said to be at the root of the problem.

‘The National Institutes of Health: Public Servant or Private Marketer?’ headlined the Dec. 22 ‘Los Angeles Times’, which revealed that while physicians have relied on the NIH to draft medical standards, the agency’s researchers accepted “substantive fees and stock from drug companies … an unabashed mingling of science and commerce.”

The NIH creates treatment guidelines for use by physicians, but documentation reveals that many of those working at the institutes to create the guidelines were quietly on the pay of the drug companies whose products they were suggesting.

“It’s more than manipulation — they (the FDA and NIH) put their seal of approval on things that they knew were false, were wrong … they’ve betrayed the trust. Instead of servants of the public, they became truly agents and promoters of the Industry,” said Vera Hassner Sharav, a renowned drug industry critic whose years of work as head of the Alliance for Human Research Protection (AHRP) broke much of the ground for today’s revelations.

“Now we’re seeing the pattern, we’re seeing that it isn’t one drug, not one company, but rather the entire enterprise,” added Hassner Sharav in an interview.

What continually resurfaces is federal agencies’ effective abdication of their watchdog role, interrupted only by scientists of integrity who have gone beyond their agency structures in attempting to alert the public to growing dangers.

Economic and political goals appear to have replaced the need to safeguard the safety of the U.S. public and agencies’ scientific integrity, say observers.

“Over the last couple of years, we … began to hear reports out of a number of the federal agencies that ‘something was going on’, that research and analysis by government scientists was being systematically censored or ignored … or misrepresented in some way,” said Kathleen Rest, executive director of the Union of Concerned Scientists (UCS).

In an interview Rest described what she saw as a “pattern,” one of “politicizing or manipulating scientific advisory boards.” The UCS — whose membership encompasses much of the cream of America’s scientists, including a number of Nobel laureates — also found “evidence and cases of agencies manipulating or suppressing scientific analysis.”

The March 2003 FDA report by the DHHS-IG, whose public release presented only information portraying the agency in a favorable light, was obtained in full under the Freedom of Information Act by the UCS and another non-governmental organization (NGO), Public Employees for Environmental Responsibility (PEER).

While the release of only the report’s positive conclusions further highlights the official spin being broadly put on research findings, all of those interviewed spoke of the devastating potential of disseminating misleading scientific data. Graham described the yearly death toll from Adverse Drug Reactions (ADRs) across the full spectrum of available medication as “massive.”

Both the ‘Journal of the American Medical Association’ and Britain’s ‘Lancet’ have described ADRs as the fourth leading cause of death in the United States. But despite such severe human costs, the full version of the DHHS-IG report revealed that about one-fifth of FDA scientists had “been pressured to approve or recommend approval” for a medication “despite reservations about the safety, efficacy or quality of the drug.”

According to Graham, “the agency (FDA) has never given a high priority to safety.” Instead he saw its main pursuit as the “review and approval of drugs,” adding that the vast majority of agency resources were expended in this effort. Accordingly, those who work in review and approval areas have the most influence upon FDA policy, he added.

Confirming reports of the pressures applied to government experts who dare to speak out, Graham warned, “intimidation of scientists who threaten the status quo at FDA is routine.”

He described how, after he sought the withdrawal of an arthritis drug called Arava, his superior addressed his concerns that the medication induced liver failure.

“The division director spent the first 10 minutes of that meeting screaming at me. Basically, standing up, jugular veins bulging in his neck, eyes sort of bugging out of his head, screaming … basically trying to intimidate me so that I’d change my conclusion.”

Arava is still on the market today.

Citing another instance, Graham recalled his 1999 attempt to have the diabetes drug Rezulin withdrawn for also inducing liver failure. He noted that while Britain withdrew the drug in 1997, the FDA delayed Rezulin’s market recall until 2000, citing a policy of “risk management,” though Graham noted that his findings already indicated the futility of such an approach.

Those marketing Rezulin “were making roughly two million dollars a day” on the medication, Graham added, so the extra market time provided a financial bonus to the medication’s makers.

The scientist also described how he was given a poor performance evaluation after providing accurate congressional testimony on drug safety shortcomings. His supervisor at the time informed him “my job was to please him,” describing that as a “direct quote.”

When asked if this meant his job was “not to safeguard the public,” Graham replied, “right, my job was to please him.”

Complicating efforts to maintain scientific integrity, Graham noted that existing federal protections for whistleblower have been gutted, and that a current whistleblower protection bill is being blocked in Congress.

Despite obvious concern over the potential ramifications for his future, Graham emphasized his belief that “my job is to look after drug safety for the American people.”

© Copyright 2004 IPS – Inter Press Service

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