October 26

FDA Regulators Accused of Trying to Quash Testimony About Cardiac Risks of Painkillers – NYT

FDA Regulators Accused of Trying to Quash Testimony About Cardiac Risks of Painkillers – NYT

Sat, 12 Feb 2005

A New York Times front page report announces that President Bush will veto any limits on the Medicare prescription drug giveaway. The administration is adamant about transfering $724 billion in taxpayer money to pay pharmaceutical companies for high cost drugs without the possibility of negotiating the price.

Some of the drugs are essential for seniors: but many of the most widely prescribed drugs offer little benefit compared to cheaper, safer drugs – and some expensive drugs covered by Medicare are downright lethal.

The NYT reports (below) that FDA officials are trying, once again, to impose a gag order on the associate director in the FDA’s Office of Drug Safety, Dr. David Graham. Dr. Graham has significant, new, scientific findings about the adverse event data relating to Celebrex and Bextra, the two marketed COX 2 anti-inflammatory drugs (both manufactured by Pfizer). Dr. Graham wants to present his findings at next week’s FDA advisory committee hearing about COX 2 drug safety issues.

As Dr. Graham points out, “this study bears directly on the whole reason why this advisory meeting is being held in the first place.”

Indeed, the FDA hearing has been convened in the wake of public outrage about the the agency’s role in concealing from physicians and the public, evidence linking Vioxx to heart attacks and strokes, resulting in tens of thousands of prevenatable deaths.

Last year, the same administrators attempted to prevent Dr. Graham from publishing his important findings about the lethal risks of Vioxx, a COX 2 anti-inlammatory drug for arthitis pain.

In his November testimony before the Senate Finance Committee, Dr. Graham disclosed the facts that FDA officials had tried to prevent the public from knowing:

“Prior to approval of Vioxx, a study was performed by Merck named 090. This study found nearly a 7-fold increase in heart attack risk with low dose Vioxx. The labeling at approval said nothing about heart attack risks. In November 2000, another Merck clinical trial named VIGOR found a 5-fold increase in heart attack risk with high-dose Vioxx. The company said the drug was safe and that the comparison drug naproxen, was protective. In 2002, a large epidemiologic study reported a 2-fold increase in heart attack risk with high-dose Vioxx and another study reported that naproxen did not affect heart attack risk. About 18 months after the VIGOR results were published, FDA made a labeling change about heart attack risk with high-dose Vioxx, but did not place this in the “Warnings” section. Also, it did not ban the high-dose formulation and its use. I believe such a ban should have been implemented. Of note, FDA’s label change had absolutely no effect on how often high-dose Vioxx was prescribed, so what good did it achieve?”

See: http://www.consumersunion.org/pub/campaignprescriptionforchange/001651.html

Dr. Graham estimates that the number of preventable heart attacks range from 88,000 to 139,000 Americans. “Of these, 30-40% probably died. For the survivors, their lives were changed forever.”

Dr. Graham’s courage and moral decision to speak out for the good of the public – even though it put him on a collision course with FDA administrators whose decisions demonstrably sacrifice patient safety to protect industry’s cash flow – earned Dr. Graham well deserved public accolades–as well as Forbes magazine “Face of the Year.” See: http://www.forbes.com/home/sciencesandmedicine/2004/12/13/cx_mh_1213faceoftheyear.html

The fundamental issue that the FDA advisory committee will most likely NOT address, is FDA’s flawed safety standard for approving new drugs. FDA’s Office of New Drugs (OND) ASSUMES that a drug is safe–unless proven “beyond a shadow of a doubt” that it is unsafe. Dr. Graham compared that standard as follows:

“When it comes to safety, the OND [FDA’s Office of New Drugs] paradigm of 95% certainty prevails. Under this paradigm, a drug is safe until you can show with 95% or greater certainty that it is not safe. This is an incredibly high, almost insurmountable barrier to overcome. It’s the equivalent of “beyond a shadow of a doubt.” And here’s an added kicker. In order to demonstrate a safety problem with 95% certainty, extremely large studies are often needed. And guess what. Those large studies can’t be done.”

“There are 2 analogies I want to leave you with to illustrate the unreasonableness of CDER’s standard of evidence as applied to safety, both pre- and post-approval. If the weather-man says there is an 80% chance of rain, most people would bring an umbrella. Using CDER’s standard, you wouldn’t bring an umbrella until there was a 95% or greater chance of rain.”

“The second analogy is more graphic, but I think it brings home the point more clearly. Imagine for a moment that you have a pistol with a barrel having 100 chambers. Now, randomly place 95 bullets into those chambers. The gun represents a drug and the bullets represent a serious safety problem. Using CDER’s standard, only when you have 95 bullets or more in the gun will you agree that the gun is loaded and a safety problem exists. Let’s remove 5 bullets at random. We now have 90 bullets distributed across 100 chambers. Because there is only a 90% chance that a bullet will fire when I pull the trigger, CDER would conclude that the gun is not loaded and that the drug is safe.”

FDA’s failure to monitor safety data after a drug is approved increases the odds that the agency’s Russian roulette risk tolerance standard will result in deaths.

Contact: Vera Hassner Sharav


February 12, 2005 A-13
Drug Regulators Are Trying to Quash Study, Senator Says

WASHINGTON, Feb. 11 – The tension and intrigue surrounding a crucial federal drug advisory committee meeting next week, already high, reached a boil on Friday when Senator Charles E. Grassley charged that top federal drug regulators intended to suppress an important study.

The panel has been convened to discuss whether Celebrex and Bextra, heavily selling arthritis pills from Pfizer, hurt the heart and are worth their potential risks. But top officials of the Food and Drug Administration have forbidden Dr. David Graham, a drug-safety officer at the agency, to discuss before the panel a large study of that very question, said Dr. Gurkirpal Singh of Stanford University School of Medicine, Dr. Graham’s co-author.

“We have significant new information that will alter the thinking about these drugs,” Dr. Singh said. “I don’t understand why they won’t let us present this information.”

Mr. Grassley, an Iowa Republican, wrote a letter Friday to the agency’s acting commissioner, Dr. Lester Crawford, demanding to know by Monday the reason for the agency’s decision.

Dr. Graham expressed frustration that F.D.A. officials had instructed him not to discuss the new study in a presentation he is scheduled to give to the committee on Thursday. “This study bears directly on the whole reason why this advisory meeting is being held in the first place,” Dr. Graham said.

Agency officials told him the study had not yet been properly vetted, he said.

A spokesman for the agency denied that Dr. Graham had been barred from presenting the new findings. He said that agency officials had simply expressed a preference “that he rely on published literature in his talk, but that it was his call if he wanted to offer data from his new study.”

The latest charge suggests that the panel will render judgment not only on the safety of Celebrex and Bextra but also on how well the F.D.A. is doing its job.

A series of controversies have called into question whether the agency has the tools or the will to protect patients’ health.

Some in Congress, including Mr. Grassley, are calling for fundamental changes at the agency. Drug-safety advocates claim that top agency officials are far too cozy with drug makers. Agency officials say they are doing a good job.

Both sides point to the story of Vioxx, a pain pill similar to Celebrex and Bextra that Merck withdrew from the market in September, an action that will also be discussed at the hearing.

“There seems to be this view that we did something wrong with Vioxx,” Dr. Robert Temple, director of the agency’s office of medical affairs, said in an interview. “What exactly is the thing that we did wrong? Approving it? Making them do a 6,000-patient study to get a claim? What?”

Mr. Grassley had a quick answer. “The Vioxx disaster and its aftermath have shaken the public’s confidence in the Food and Drug Administration,” he said, in part because, instead of listening to its best scientists, the agency is “sitting down to negotiate with drug companies.”

Vera Sharav, president of the Alliance for Human Research Protection, said that the Vioxx story demonstrated that “the F.D.A. has abandoned its public responsibility to protect us from unsafe drugs and is standing by as drug companies market lethal drugs.”

A Merck spokeswoman said that the company had acted appropriately in its research, marketing and eventual withdrawal of Vioxx.

Pfizer representatives say that studies show that Celebrex and Bextra are safe.

There is a sense of déjà vu to Dr. Singh’s latest charge. The agency convened an advisory panel a year ago to discuss whether antidepressants cause children and teenagers to become suicidal. Dr. Andrew Mosholder, another drug-safety officer for the agency, had concluded that the drugs did increase the risks of suicide. Top officials were skeptical of his findings and would not let him testify about his data before the panel.

A second study eventually confirmed Dr. Mosholder’s conclusions, but the agency’s refusal to let Dr. Mosholder testify caused a firestorm of criticism and prompted Mr. Grassley to begin an investigation of the agency.

The advisory panel will meet for three days beginning on Wednesday. It already has a mountain of data to sort through.

At the end of the hearings, the committee will be asked whether Celebrex and Bextra should be withdrawn or whether warnings on their labels should simply be strengthened.

The committee may debate whether the withdrawal of Vioxx was appropriate. And the committee will also discuss what, if any, studies of the drugs should be undertaken, according to F.D.A. documents.

Copyright 2005 The New York Times Company

FAIR USE NOTICE: This may contain copyrighted (© ) material the use of which has not always been specifically authorized by the copyright owner. Such material is made available for educational purposes, to advance understanding of human rights, democracy, scientific, moral, ethical, and social justice issues, etc. It is believed that this constitutes a ‘fair use’ of any such copyrighted material as provided for in Title 17 U.S.C. section 107 of the US Copyright Law. This material is distributed without profit.

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