What Do Rats Smell Like, Anyway?

The FDA’s latest campaign to protect the profits of a drug company over the safety of Americans is unprecedented, and the organizers include a gang of current and former FDA officials largely credited with turning the nation’s regulatory beagle into a lapdog for Big Pharma under the Bush Administration.

FDA spokesman Douglas Arbesfeld, apparently the industry’s new inside guy, kicked off the campaign by sending an e-mail to journalists which was intended to discredit Dr Steven Nissen and the Cleveland Clinic. Dr Nissen’s study appeared online on May 21, 2007, in the New England Journal of Medicine and warned that GlaxoSmithKline’s diabetes drug Avandia increased the risk of heart attacks by 43% and death from cardiovascular events by possibly 64%.

The talking points for the media appear to have been formulated and agreed upon ahead of time between Arbesfeld and others (see below) because more than one story from ostensibly different sources later appeared in the media and on the internet referring to Dr Nissen with such names as “St Steven”, “Patron Saint of Drug Safety” and “Saint Steven the Pure.”

In his email to journalists, Mr Arbesfeld pasted portions of an article which appeared on the Heartwire website, containing umpteen critical comments about Dr Nissen and the Avandia study, as well as comments made by an anonymous blogger on the internet who said that business at the Cleveland Clinic is run similar to a Mafia TV series. The full bog states:

“Wake up pharmaceutical companies, this is a call from Dr. Nissen, if you don’t hire the Cleveland Clinic for your big trials then you face the firing squad from Nissen and Company.”

“The Cleveland Clinic was one of the most respected names in medicine, now they are positioning themselves as candidates to take over for a new series on HBO to replace the Soprano’s ” the Clinico’s ‘next week who should we wack ……’ ” Bata bing bata boon. Comment by Brian A – May 22, 2007.”

However, it could just as easily be inferred that Mr Arbesfeld authored the slanderous blog and supplied it to Heartwire with the intention of quoting it later from a “reputable web site. For its part, Heartwire has since removed what it says are “unsubstantiated remarks about Dr Nissen and the Cleveland Clinic,” and states: “In retrospect we regret that we published those sentences, as they do not meet the highest standards of journalistic or scientific integrity or credibility.”

The smear campaign has federal lawmakers up in arms. At a June 6, 2007 hearing before the House Oversight and Government Reform Committee, in response to questions about Mr Arbesfeld sending the e-mail under his official title of FDA spokesman, FDA Commissioner Andrew von Eschenbach told the lawmakers, “It was an inappropriate and unfortunate act on the part of an individual which has been addressed through disciplinary procedures.”

Dr Nissen is none too happy about the stunt either. “I’m a pretty tough guy,” he told ABC News on May 30, 2007, “but I’ll tell you, having this kind of an e-mail that questions my motives, broadcast to the major journalists with whom I work and have established a reputation, is — it’s an outrage.”

As for his part, Mr Arbesfeld told the Boston Globe that the email reflected his own personal views and not the FDA’s. Any assertion that the email reflected his own personal views is not quite credible considering that his previous employment was always promoting the views of the industry.

A few articles in the media mentioned that Mr Arbesfeld worked for Johnson & Johnson, but his employment with public relations firm Manning Selvage & Lee was not noted. On December 16, 1999, the Healthcare Marketing & Communications Council reported that Mr Arbesfeld had joined Manning as Senior Vice President in New York.

On January 5, 2001, the firm issued a press release to announce the promotion of Mr Arbesfeld and others and referred to Manning as “one of the largest healthcare practices worldwide and has a broad array of clients including Allergan, Amgen, Eli Lilly and Company, Genentech, Hoffmann La-Roche, Kaiser Permanente, Novartis, Pharmacia and Procter & Gamble.”

In reading the press release, Mr Arbesfeld’s expertise with using the Internet is apparently a bi-product of his work for Manning. “In this role,” it said, “Arbesfeld will help healthcare clients maximize internet-relations in the marketing and communications mix, and will expand the Practice’s strategic e-product offerings.”

On August 5, 2002, Arbesfeld identified himself in a Reuters article as representing none other than Glaxo, along with six other drug giants including Bristol-Myers, Aventis, J&J, AstraZeneca, Abbott Labs and Novartis, in a campaign to promote the “Together Rx” prescription drug card program for senior citizens. In 2005, the Reporters Handbook listed him as the contact person for J&J subsidiaries, Janssen Pharmaceutica, Ortho-McNeil Pharmaceutical and Ortho Biotech Products.

Less than a week after Mr Arbesfeld’s hatchet job on Dr Nissen, ex-FDA Deputy Commissioner Dr Scott Gottlieb planted an editorial in the May 29, 2007, Wall Street Journal entitled, “Journalist Malpractice,” accusing the New England Medical Journal of intentionally publishing the Nissen study to make the FDA look impotent. “The publication was timed,” he wrote, “to get ahead of the Food and Drug Administration’s more careful evaluation of the same issues.”

“The journal seemed bent on beating the FDA to the punch,” Dr Gottlieb claimed.

“The goal?” he said, “Painting the FDA as impotent, in order to argue for legislation winding through Congress that would increase regulatory hurdles for drug approvals.”

The only problem with the Nissen-NEJM conspiracy theory is that the issue under investigation in Congress right now is why the FDA did not warn the public about Avandia heart risks six months before the Nissen study was ever published.

In the end, when it comes to “Journalistic Malpractice,” the larger question would seem to be how was it that so many industry shills were able to get the major media outlets and medical journals to immediately publish commentaries and editorials attacking the NEJM and the Nissen research with headlines splashing all over the internet.

In his editorial, Dr Gottlieb notes that there are “questions” whether Avandia is associated with heart risks, but says they are “so far unsupported by more rigorous, randomized studies and extensive review by the FDA and other authorities around the world.”

“When it comes to the issue du jour, drug safety,” he wrote, “no description of medical research in a medical journal comes close to the detail level or scrutiny imposed by the FDA on study results before approval.”

Assuming this is true, the problem is that the industry insiders running the FDA refuse to act on the advice of the agency’s top scientists with first hand access to the underlying data. In a July 26, 2007 speech on the Senate floor, Senator Charles Grassley (R-Iowa), of the Senate Finance Committee, said that, in the case of Avandia, “Not only did the FDA disregard the concerns and recommendations from the office responsible for post-marketing surveillance, but I have found that it also attempted to suppress scientific dissent.”

In the past two months, he told his fellow senators, “I’ve had to write to the FDA regarding the suppression of dissent from not one but two FDA officials involved in the review of Avandia.”

The Heartwire website conveniently echoed Dr Gottlieb’s sentiments by featuring portions of a May 23, 2007, unsigned editorial from the medical journal The Lancet, which claimed that the verdict on Avandia should await the results of a Glaxo sponsored trial called RECORD, not due out until 2009.

“Taken together,” the editorial said of Dr Nissen’s findings, “these results, although based on very small numbers of events, certainly raise a signal of concern and indicate the need for more reliable information about rosiglitazone’s safety.”

“But the FDA, physicians, and patients can reasonably await the results of RECORD, a phase 3 trial designed specifically to study cardiovascular outcomes,” it said.

“Until the results of RECORD are in,” the Lancet noted, “it would be premature to overinterpret a meta-analysis that the authors and NEJM editorialists all acknowledge contains important weaknesses.”

The problem with waiting two years for the results of the RECORD trial is that FDA scientist Dr David Graham reviewed the results of this study thus far and told an FDA advisory panel that the study design is so flawed that the results should not be considered in any risk benefit analysis of Avandia now, or in 2009.

In fact, Dr Graham says the RECORD study is so useless that it is probably unethical to allow it to continue because no possible benefit can be achieved by allowing it to go on and that Avandia should be pulled off the market now because thousands of patients are being injured each month by using the drug.

At the end of his editorial, Dr Gottlieb lists himself as a physician and a resident fellow at the American Enterprise Institute, as well as former Deputy Commissioner of the FDA from 2005 to 2007. However, back on August 24, 2005, the Seattle Times provided a much better picture of his background and highlighted the oddity of the FDA hiring him in the first place in light of his solid alliance with the industry. “Only a month ago,” the article states, “Dr Scott Gottlieb was a Wall Street insider, promoting hot biotech stocks to investors.”

At the time, the Times noted, “Now Gottlieb holds the No. 2 job at the federal agency that approves new drugs, oversees their safety and affects the fortunes of companies he once touted.”

“Now, as one of three deputy commissioners,” the article said, “Gottlieb will help oversee such major policies as the FDA’s fast-track approval process for drug and biotech products, a priority for many Wall Street funds and the pharmaceutical industry.”

The Times also noted that a half-dozen current and former FDA officials said they did not know of anyone else from Wall Street ever moving directly into such a high-level job at the agency.

A couple months later, the November 12, 2005, Boston Globe reported that Dr Gottlieb could not participate in formulating the nation’s defense plan against the avian flu due to conflicts of interest. He “was recused from key parts of the planning effort because his past consulting work for Manning Selvage & Lee involved companies whose products would be used to combat a flu pandemic,” it said. Yes, the very same Manning Selvage & Lee at which Arbesfeld held the Senior Vice President position. Does anyone smell a rat (or several)?

The article pointed out that Dr Gottlieb’s former clients included Roche, the manufacturer of Tamiflu, and Sanofi-Aventis, the parent company of the nation’s sole flu vaccine maker.

According to the Globe, Manning paid Gottlieb a $12,500 monthly retainer for nine months for projects that included eight companies, and he was also paid $9,000 for private consulting work for VanGen Inc, a firm that won a $878-million contract to supply the US government with 75 million doses of anthrax vaccine.