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relenza and the fda RELENZA AND THE MYTH OF FREE SPEECH AT THE FDA
Release Date 2005-07-01
Time 08:42:00
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JILY 1, 2005. As the viral prophets of doom step up warnings of an imminent global flu pandemic, it's instructive to examine the drugs that are being recommended to treat the flu.

Here, from 2000, is a CBC piece on Dr. Michael Elashoff, an employee of the FDA. Elashoff made a career mistake. At a panel meeting, he spoke out against impending FDA approval of Relenza (manufactured by Glaxo).

Elashoff presented his case so effectively, other panel members sided with him and turned down the drug.

Glaxo, expecting a rubber-stamp from the FDA, was outraged.

Soon after, Elashoff was told he would not be participating in any more panels on controversial medications; he should consider leaving his division at the FDA.

Another panel reconvened, and Relenza sailed through to approval.

Interestingly, the drug was never thought to be more than "modestly effective," even by its advocates. It might shorten the duration of the flu by one or two days.

However, with proponents agreeing that this effect constituted a significant treatment, the all-important certification by the FDA would open the door to major sales dollars for Glaxo.

It, of course, remains a mystery as to how a doctor or researcher can estimate the probable duration of the flu in a given person to begin with.

Certainly, many nutritional practitioners can devise protocols for some patients that will make the flu disappear more quickly than usual. However, obtaining FDA certification for such a protocol would involve spending millions of dollars, at the end of which ordeal the chance of a green light would---due to institutional bias---amount to zero.

In the case of Dr. Elashoff, it's not hard to see that his silencing by his FDA bosses illustrated that bias. Why else would he be punished for presenting his data and interpretation at a panel meeting, when the supposed purpose of the panel was to examine Relenza carefully, from several points of view, in order to decide whether it was worthy of approval?

A sign was raised: WE HAVE AN UNDERSTANDING WITH GLAXO. DON'T ROCK THE BOAT.

CBC MARKETPLACE
Controversial flu drug approved despite scientist's protests
Broadcast: November 7, 2000 | Producer: Christian Côté; Reseachers: Cindy Bahadur; Mike Gordon

"I felt I was making a difference and I sort of saw myself as trying to get to the real story," says Dr. Michael Elashoff.

It's flu season -- and you may have heard of a new flu drug called Relenza.

It came onto the market last year with promises to make you better, quicker than anything previously on the market.

What you might not have heard about were the efforts of an American scientist who tried to keep Relenza off the market.

The manufacturer, Glaxo Wellcome, promised that Relenza would kill the flu virus and make you feel better up to a day and a half sooner. The cost: $50 for a five-day prescription.

In the aftermath, doctors lined up on both sides of the fence - those who hailed a new flu treatment and others who were skeptical.
Who do you believe?

Marketplace went to Washington, where it's up to the U.S. Food and Drug Administration to say yes or no to a new drug getting on the American market.

We met a committed young scientist, who felt the wrath of his FDA bosses and the drug manufacturer when he tried to keep Relenza off the market.

Not long ago, Dr. Michael Elashoff was a valued employee of the FDA. His job was to do statistical reviews of new drug applications.

[CBC sidebar to this article: Treating the flu with Relenza---You must see your doctor within 48 hours of suspecting that you have the flu. Even then, studies suggest that at least half of all doctor diagnoses of flu are wrong. In some cases, the illness could be a more serious bacterial infection.]

But these days Elashoff is poring over his resumé, not numbers. He walked away from his promising career, because of a drug he concluded was not effective - and should not be approved. It's a conclusion for which he has paid a price ever since.

Scientist skeptical over Relenza's merits
Elashoff made his stand at a crucial FDA advisory committee meeting in February of 1999, where his team gave their scientific review of Relenza. The committee was then to advise the FDA whether to approve the drug.

Elashoff had analysed data from three drug trials conducted by the maker of Relenza - Glaxo Wellcome.

One trial studied the effects of Relenza on a European population sample, the second studied people who lived in the Southern Hemisphere, the third - and largest - looked at North Americans.

"Glaxo Wellcome claimed that in North America, Relenza decreased the overall length of flu by one day," Elashoff told Marketplace.

"The analyses I did suggested that even one day was an overestimate, and anywhere from a third of a day on down to no effect at all is what I would consider a reasonable estimate of the drug's full effect."

Glaxo Wellcome, citing two studies outside North America, said Relenza reduced flu symptoms by one to two-and-a-half days.
Company officials took the floor at the committee meeting confident of its results because the method it used to measure that reduction in symptoms had been agreed to by the FDA before the trials.

But when Elashoff took the floor, he gave a much different interpretation.

With the approval of his bosses, Elashoff tested the trial data several different ways - not just the method agreed to by Glaxo Wellcome and the FDA.

"The North American study was as large as the other two studies put together," Elashoff said. "It was almost a complete failure in the sense that people who received nothing did just as well as people who received Relenza."

Elashoff's findings hit home. Thirteen of 17 committee members voted Relenza did not demonstrate its effectiveness - and should not be approved. Some said they were reluctant to vote no. One called the new drug a base hit, but not a home run.

Glaxo Wellcome disputes Elashoff's findings
Just days after striking out with the Advisory Committee, Glaxo Wellcome sent a seventeen page letter to the FDA. The letter, obtained by the CBC, detailed a number of procedural problems with the Committee.

The pharmaceutical company's chief concern was Michael Elashoff. The letter mentioned him 30 times. Glaxo Wellcome protested his interpretation of their numbers.

The company said Elashoff's method wasn't what it agreed to before the trials. Glaxo Wellcome called Elashoff's work flawed, extreme and inappropriate.

[Another CBC sidebar to this article---Some (Canadian) provinces won't cover drug Relenza costs about $50 for a five day prescription. It's not covered by any provincial drug plan. Some of the provinces told Marketplace they won't cover it because they share Michael Elashoff's conclusion that the drug is not an effective treatment.]

A couple of weeks later, the FDA requested more trial data and analysis from the drug company. A few months later, the FDA approved Relenza for sale in the United States. It said the additional information resolved the concerns raised by the Advisory Committee. Although the FDA admitted the drug had only "modest clinical benefit."

In the fall of 1999, Health Canada reviewed the same evidence and approved the sale of Relenza in this country - in time for last year's flu season.

Reports of Reactions
Michael Elashoff stands by his initial conclusions about Relenza. It should not, he says, be on the market.

Since it hit the market, there have been some risks associated with the use of Relenza. In the United States, there have been reports of serious adverse reactions - especially in patients with respiratory problems such as asthma.

Elashoff's findings point to regional differences
Michael Elashoff found that Relenza appeared to be less effective on North Americans than on Europeans and people who live in the Southern Hemisphere. One difference in the groups of people studied, he found, was that North Americans used acetaminophen and cough syrup while taking Relenza, much more than the other two groups. Suggestions were made that these over the counter drugs might work to reduce flu symptons or work against the effectiveness of Relenza - but no conclusions could be drawn.

In July of this year, Glaxo Wellcome added a warning that reads Relenza "... is not generally recommended for treatment of patients with underlying airways disease because of the risk of serious adverse events..."

Health Canada has received sixteen reports of suspected adverse reactions to the drug in the first seven months it was on the market - and one death was associated with the use of Relenza.

In response, a Glaxo Wellcome spokesperson told Marketplace, "there has been no report to my knowledge of any fatality in which Relenza has been confirmed as the cause... When appropriately prescribed, Relenza is well tolerated and it is effective."

Career Troubles
Michael Elashoff says his career went downhill after he told the FDA Advisory Committee that Relenza was not effective in North America. His bosses, he said, made him feel as though he had done something wrong.

"They were very upset," Elashoff said. "I was sort of a convenient person to blame for it. And within fairly short order, I was told that I wouldn't be reviewing the other flu drug, Tamiflu, that I'd been scheduled to work on."

Dr. Larry Sasich is a pharmacist and a consumer advocate with the Public Citizen Health and Research Group in Washington. He's also a critic of the relationship between the FDA and drug companies.
We showed Sasich the letter Glaxo Wellcome wrote after Elashoff told the committee that Relenza was not effective in North America.

"It sounded like it was written by a very angry 900 pound gorilla drug company that was having a temper tantrum because it thought it had a slam dunk on a new drug with a potential half a billion dollar market," Sasich said.

Sasich added that he's heard of FDA medical reviewers being transferred after recommending a drug not be approved.
That's what happened to Michael Elashoff.

"I was told I wouldn't be doing any more advisory committee meetings," Elashoff said. "I wouldn't be working on any drugs that were quote unquote, controversial. And there was the suggestion, it's probably better if you leave the division."

Elashoff reluctantly took the transfer. But after several months, he left the FDA, disillusioned by the Relenza experience.

Marketplace wanted to talk to the FDA about their former employee, but they refused, saying they could not comment on a personnel matter. We also asked Glaxo Wellcome for an on-camera interview. They, too, refused.

Michael Elashoff landed on his feet. He received several job offers within weeks of leaving the FDA last August. He now works for a genetic research company.

end CBC article