December 12, 2011

FRANCE: Scandal Over Mediator, a French Weight-Loss Drug, Prompts Calls for Wide Changes


PARIS, France / Herald-Tribune.com / Health / December 12, 2011

By Scott Sayare

PARIS — In 33 years on pharmacy shelves here, the diabetes drug Mediator was prescribed to an estimated five million French patients, many of them diabetics, many others hoping simply to lose weight. When French authorities ordered the drug off the market in 2009, alerted to possible cardiovascular risks, there were 300,000 active prescriptions.

Mediator and its enigmatic French manufacturer, Laboratoires Servier, a privately held company with a troubled past, find themselves at the center of France’s largest public-health scandal in at least a decade. Health officials estimate that as many as 2,000 people died, with thousands more hospitalized, victims of cardiac valve damage and pulmonary hypertension apparently linked to the drug.

Politicians and the press have pilloried Servier, charging that it concealed the dangers of Mediator for decades and insisting that the company has a wider history of disregarding health concerns about its products. Many have noted that two Servier weight-loss products, both closely related to Mediator, were at the center of the fen-phen scandal of the late 1990s in the United States.

In France, government investigators have accused Servier of licensing Mediator as a diabetes drug to avoid scrutiny, but urging doctors to prescribe the pills as a diet aid to bolster sales — a practice that greatly expanded the pool of those potentially harmed by the drug. Magistrates are investigating the company on charges of consumer fraud and manslaughter, and a public prosecutor has charged Servier with defrauding the French health care system. Trials are expected next year.

There are broader implications, as well. Drug makers have long viewed France’s pharmaceutical oversight apparatus as being relatively permissive, in particular as compared with the United States Food and Drug Administration, which industry and some patient groups criticize as overly cautious. French political leaders say that the Mediator scandal has exposed the failings of the country’s regulatory system, which they have described as rife with conflicts of interest and marked by a distinct apathy toward questions of public health.

The head of the French regulatory body, known by its acronym Afssaps, resigned this year, and French senators approved a package of reforms in October.


French Labour minister Xavier Bertrand delivers a speech during the weekly session of questions to the government on December 7, 2011 in Paris.“We want there to be a ‘before’ and ‘after’ as regards Mediator in our country,” said Health Minister Xavier Bertrand, addressing the Senate. Getty Images

Servier says it did nothing wrong and has insisted that the discovery of the dangers of the drug, also known as benfluorex, depended in part upon recent advances in echocardiography.

“I don’t see at what point Mediator could have been caught sooner,” said Lucy Vincent, a spokeswoman for Servier.

The withdrawal of Mediator from the market in 2009 — it was then available in France, Luxembourg and Portugal — caused little stir. Only the following year, with the publication of a book titled “Mediator 150 mg: How Many Dead?” did the news media and government officials take serious note.


“I realized they were withdrawing the drug on the sly,” said the book’s author, Dr. Irène Frachon, a pulmonologist. Servier and the health authorities made little effort to alert former patients, she said, like “a car manufacturer who sees there’s a defect in the brakes of its car, and who corrects the defect in its production line but doesn’t warn the people who have the car.”

In 2007, Dr. Frachon was among the first to identify the apparent risks of Mediator. Her book prompted lawsuits, public outcry and a government inquiry.

In January 2011, the interministerial commission leading the inquiry charged that Servier had deceived health authorities and patients in order to keep Mediator on the market.

But in their report, investigators also wrote that health officials had ignored a series of warning signs beginning a decade before. They additionally found that regulatory decisions taken by the Afssaps, the drug licensing agency, were in fact a “co-production,” reached in “cooperation” with drug makers.

At the Afssaps, voting members of the approval committee have long served simultaneously as consultants or employees of the pharmaceutical firms they are meant to regulate, officials acknowledge. And while members are expected to declare conflicts of interest, there are no penalties for not doing so. Consultants or employees from various companies, including Servier, remain active participants even now, according to Ms. Vincent, the Servier spokeswoman.

In America Food and Drug Administration restrictions on conflicts of interest are more rigorous, French and American health officials say. Failure to report a conflict of interest is a crime.

Gérard Bapt à l'Assemblée Nationale
“It’s a matter of culture,” said Dr. Gérard Bapt, a cardiologist and a member of Parliament who has worked on the Mediator case. French health professionals and public officials often dismiss conflicts of interest as irrelevant, he said.


Dr. Gérard Bapt speaks in the National Assembly

Dr. Frachon agreed, attributing that attitude to a certain sense of pride. “We’re the nation of the Enlightenment,” the logic goes, she said, “and we don’t have to take moral lessons from anyone.”

Additionally, in the United States, the specter of class-action lawsuits imposes a higher level of precaution on the part of drug makers, Dr. Bapt suggested.

French law provides for no equivalent legal actions. The fen-phen scandal, which prompted two Servier drugs to be pulled from the market after being linked to severe heart damage, brought a huge class-action settlement and thousands of separate claims in the United States. Wyeth, which had licensed the drugs for the American market, set aside more than $20 billion to pay patient damages. In France, lawsuits connected to the same drugs — have seen a payout of no more than 2 million euros (about $2.7 million), Dr. Bapt said.

The recently approved legal changes, known as the “post-Mediator” rules and partly inspired by the American Physician Payments Sunshine Act, will not create the possibility of class-action suits here. But the reforms, to take effect in the spring, would put in place sanctions for Afssaps committee members who fail to declare conflicts of interest. Interactions between doctors and drug companies are to be more strictly limited, as well.

While they publicly hail the changes, however, some in the pharmaceutical industry insist that the outrage over Mediator cannot be fully explained by the revelations in the case so far. Rather, they say, the public appears shocked by the moral complexities of drug development — by the realization that all medications involve the weighing of benefits and risks, and that even the most honorable evaluators make mistakes.

“There is no public knowledge or acknowledgment of what medicines really are, their limits,” said Ms. Vincent of Servier. “They want to believe in the miracle.”

“Mediator was a drug like any other drug, with its advantages, because it certainly had its advantages, and unfortunately this major disadvantage, which came to light very late,” she continued. “That’s the tragedy of the story.”

Muriel Rousset, 45, began taking Mediator to lose weight shortly after the birth of her second son, in 1998. In 2006, she underwent open-heart surgery to replace two damaged heart valves; she continued to take Mediator, not knowing the drug may have caused her heart problem.

In an interview, she recalled hearing French health officials explain last year that “all medicines are dangerous.”

Muriel : «Je vis avec cette épée de Damoclès»

“Well, wait,” Ms. Rousset said. “For me, as a citizen, I don’t know that medicines are dangerous. A medicine is made to save a life, to bring health, to make things better. And not to kill us.”

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