FDA Officials Form Hit Squad to Protect Avandia Profits

Evelyn Pringle August 2007

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 were obviously agreed upon ahead of time because the stories that appear on the internet refer to Dr Nissen with names like “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 which 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 to 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 email expertise 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, he 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.”

There is no doubt much truth to this assertion, but the problem is that the industry insiders running the FDA refuse to act on the advice of the agency’s top scientists. 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 a July 26, 2007 report.

In fact, Dr Graham says the RECORD study is so useless that it’s 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 who was 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.”

“Now Gottlieb holds the No. 2 job,”” the Times notes, “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.

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.

In communicating with the FDA, lawmakers have mentioned that they found it “troubling” that Mr Arbesfeld might be trying to settle old scores with Dr Nissen because they were on opposite sides regarding the approval of the heart failure drug Natrecor.

However, Dr Nissen and Dr Gottlieb’s disputes go way back as well. In fact, on August 2, 2006, they participated in a debate on the topic: “Government Science Panels: Fair and Balanced?” sponsored by the Center for Science in the Public Interest, and reported on by Russell Mokhiber and Robert Weissman in Common Dreams.

Much to his credit, Dr Nissen openly communicated his objections to the industry’s infiltration of the FDA. While sitting right next Dr Gottlieb, he candidly described the conflicts of interest which he stated were “evident at the highest levels of the FDA.”

“For years,” he said of FDA leadership, “we had an interim FDA Commissioner, Lester Crawford, who shortly after confirmation, abruptly resigns, apparently because he and his wife owned stock in regulated companies.”

“Then the administration appointed Andrew von Eschenbach as interim commissioner creating another conflict,” he said. “In his role as director of the National Cancer Institute, von Eschenbach must seek FDA approval for human testing or approval of new cancer drugs, an obvious conflict,” he noted.

“But even worse,” Dr Nissen stated, “the administration appointed Scott Gottlieb as deputy commissioner.”

“He came to this job with no regulatory experience, directly from Wall Street, where he served as a biotech analyst and stock promoter,” Dr Nissen told the audience.

Dr Gottlieb’s response to Dr Nissen’s comments was basically that he would not dignify the comments with a response.

Firms that Dr Gottlieb was involved with prior to his gig at the FDA, according to the Globe, also include the Inamed Corp, one of two companies that were seeking to return silicone gel implants to the market and on November 17, 2006, the FDA announced that it would lift restrictions on the sale of the implants.

When Dr Gottlieb left the FDA, he headed right back to greener pastures with the drug giant Novartis. The press release to announce his hiring read: “Bench International Places Eminent Regulatory Advisor Scott Gottlieb, M.D., as Senior Counsel to Novartis.”

“Under an exclusive consulting agreement,” the release stated, “Scott Gottlieb, M.D., will provide advisory services to Novartis on matters of global regulatory policy and strategy.”

The FDA recruited two members of its alumni, Peter Pitts and Robert Goldberg, to take another swipe at Dr Nissen in a June 6, 2007, commentary in the Washington Times, using the same talking points as the anonymous blogger, by referring to Dr Nissen as a “self-appointed and media-anointed Patron Saint of Drug Safety” and “Saint Steven the Pure.”

For much of the childish commentary, they poke fun at Dr Nissen because he acknowledged in the NEJM that he consults for many drug companies but said he “requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction.”

At the end of the commentary, Mr Pitts says he is a former FDA associate commissioner, and both men list their affiliation with the Center for Medicine in the Public Interest; but as usual, that listing really does not give credit where credit is due.

On its web site, the Center describes itself as “a non-partisan, non-profit educational charity,” and Mr Pitts is indeed listed as President, but his bio also says he is the Senior Vice President for Global Health Affairs at none other than Manning, Selvege & Lee.

The Manning firm apparently fills two important roles. It’s a breeding ground for industry moles preparing to enter “public service” and serves as an employment hub for industry shills once they finish their on average 2- to 3-year stint inside the Bush Administration.

In his CMPI bio, Mr Pitts describes his duties as the FDA’s Associate Commissioner from 2002 to 2004 as serving as the agency’s “Chief Messaging Officer.”

On June 7, 2007, Mr Pitts had this to say in defense of fellow hit-man Mr Arbesfeld on the Pharmalot web site: “I know Doug Arbesfeld and he is a guy devoted to advancing the public health.”

According to Mr Pitts, in sending the derogatory e-mail about Dr Nissen to journalists, Mr Arbesfeld was just standing up for the FDA and that people should know about the sacrifice he made by accepting a job in government.

“He is also a guy,” Mr Pitts says, “who took a pretty significant pay cut to put in some time in public service.”

Some would no doubt argue that it’s difficult to imagine that Mr Arbesfeld will end up in the poor house as a result of serving as the top industry mole inside the FDA.

Mr Pitts’ sidekick, Mr Goldberg, is indeed listed as the vice president of CMPI, but Mr Goldberg’s bio also says he used to be Director of the Manhattan Institute’s Center for Medical Progress and Chairman of its 21st Century FDA Task Force.

In fact, a review of the CMPI web site turned up a whole nest of ex-moles who served the industry in one capacity or another in the Bush Administration’s FDA. For instance, Daniel Troy, the former FDA Chief Counsel, also known as the “Godfather of Preemption,” sits on this “charity’s” Advisory Board.

His bio points out that he “played a principal role in FDA’s generally successful assertion of preemption in selected product liability cases.”

This “assertion of preemption” says that, as long as the FDA has approved a drug and its label, private citizens in state courts cannot sue the drug company for failing to warn about a product’s serious health risks, even in cases where it can be shown that the company concealed studies that revealed the risk from the public and the FDA.

Now that he’s switched back to private practice, Mr Troy’s CMPI bio says he currently specializes in constitutional and appellate litigation, as well as strategic counseling with “particular focus” on what else – clients regulated by the FDA.

The Advisory Board also includes, Tomas Philipson, whose bio says he served as the Senior Economic Advisor to the commissioner of FDA during 2003 and 2004 and as the Senior Economic Advisor to the administrator of the Centers for Medicare and Medicaid Services in 2004 and 2005.

That would mean that Mr Philipson served Mark McClellan, and they are now apparently joined at the hip because, as part of a program called “Patient-Centric and Prospective Medicine,” CMPI says it has created the Patient-Centric Health Forum and that Mr McClellan, “former Medicare administrator and FDA commissioner, will chair the group.”

So, it would appear that anyone looking for the retirement home for industry hit men who served in the Bush Administration’s FDA can find it right in the middle of cyberspace on the CMPI web site.

(This article is part of the Avandia Update series sponsored by the Baum Hedlund law firm)

Lawmakers Say FDA Better Clean Up Its Act

Evelyn Pringle February 2007

For six years, the Bush administration has placed pharmaceutical industry interests ahead of public interest by appointing persons with strong ties to drug companies to high level positions at the FDA, and as a result, Congressional investigations and a recent survey indicate that the health and safety of all Americans is being compromised. 

On July 20, 2006, the Union of Concerned Scientists published the results of a survey that showed an insidious political influence of science within the FDA. According to the UCS press release, the survey was co-sponsored by Public Employees for Environmental Responsibility (PEER), and was sent to 5,918 FDA scientists.

The survey found that 61% of the responding scientists knew of cases where the “Department of Health and Human Services or FDA political appointees have inappropriately injected themselves into FDA determinations or actions.”

In responding to the survey, one scientist wrote: “Over the last several years I have noticed a significant increase in the number of decisions that have become politicized (e.g., increasing requests to review even simple regulations and changes, both by Congress and the Commissioner’s office and to make apparently politically-motivated changes in language and sometimes to alter bottom line results), and I think the integrity of scientific work could be improved by minimizing the ‘politics’ of the process.”

Out of the nearly 1000 scientists who responded, close to one-fifth or 18.4%, said they had “been asked, for non-scientific reasons, to inappropriately exclude or alter technical information or their conclusions in a FDA scientific document.”

In addition, 40% of the scientists said they fear retaliation for voicing safety concerns in public and more than one-third said they did not feel they can express safety concerns even inside the agency.

The survey also found that only 47% think the “FDA routinely provides complete and accurate information to the public,” and 81% agreed that the “public would be better served if the independence and authority of FDA post-market safety systems were strengthened.”

In a complaint aimed at the FDA’s Office of Regulatory Affairs, one scientist said it should “not ostracise scientists or black ball them because their foresight sees a problem with a drug, device, food, biologics, etc. that possess a potential hazard to health now or in the future.”

In response to the concerns raised by FDA scientists, the UCS recommends:

–  Accountability: FDA leadership must face consequences if they side with commercial or political interests and not with the American people.

–  Transparency: Scientific research and reviews should be open so any undue manipulation is immediately apparent.

–  Protection: Safeguards must be put in place for all government scientists who speak out.

“These disturbing survey results make it clear that inappropriate interference is putting people in harm’s way,” said Dr Francesca Grifo, Senior Scientist and Director of UCS’s Scientific Integrity Program, in the press release.

“All federal scientists,” he said, “need protections so they can speak out when their science is manipulated, and all federal agencies need fully functioning independent advisory committees.”

“FDA leaders,” Dr Grifo noted, “should act now to improve transparency and accountability and renew respect for independent science at the agency.”

“FDA leadership,” he stated, “must understand and support independent science and it is up to Congress to hold them accountable.”

But nothing about this survey is news to FDA officials. By use of the FOIA, the UCS and PEER, recently obtained a copy of a previously unpublished survey by the Health and Human Services Office of Inspector General from late 2002, that polled 846 FDA scientists, and with nearly half responding determined that:

Nearly one in five said that they “have been pressured to approve or recommend approval” for a drug “despite reservations about the safety, efficacy or quality of the drug”

Two-thirds lacked confidence that the FDA “adequately monitors the safety of prescription drugs once they are on the market”
Only 12% of the responding scientists were completely confident that FDA “labeling decisions adequately address key safety concerns,” and 30% were not at all or only somewhat confident
More than one-third were not at all or only somewhat confident that “final decisions adequately assess the safety of a drug”
Despite the above results, the report published by the OIG in March 2003, included the conclusion that FDA scientific reviewers “have high confidence in decisions FDA makes.”

On August 8, 2006, the UCS briefed acting FDA Commissioner, Andrew von Eschenbach, on the latest survey and discussed the political inference at the FDA. To restore integrity, UCS recommended that Dr von Eschenbach adopt and enforce three basic commitments:

(1) to ensure that data or results are never softened for any audience. Rigorous scientific debate must be valued at the FDA;

(2) to pledge to support scientists who speak out by taking adverse employment action against any manager who retaliates against a reviewer; and

(3) to commit to a culture that supports a collaborative process of testing and challenging scientific hypotheses.

Along with the recommendations, the group’s August 8, 2006, press release said, “The FDA must allow an open scientific process and recognize the need for scientists to pose and answer questions without consequences related to their status at the FDA.”

Critics claim that a major issue that needs to be addressed involves the rampant conflicts of interest among members of the FDA’s advisory panels who have financial ties to the pharmaceutical industry. In November 2005, a new law was passed that required members of the committees to disclose all financial ties to drug companies.

The categories for disclosure were broken down into dollar amounts and time frames, such as less than $10,000 a year or between $10,000 and $50,000 a year. After reviewing the financial disclosure forms, the FDA is permitted to grant waivers that allow experts to sit on panels even if they have financial ties to a drug company.

However, on April 21, 2006, the Boston Globe discussed the practical effects of the law since it was enacted and reported that FDA critics “say the new transparency has changed little, and scientists who have conflicts of interest can still guide FDA decision making.”

In less than 6 months after the law went into effect, the Globe determined the FDA had granted close to 100 waivers.

One of the latest FDA fiascoes, involves the approval of the antibiotic, Ketek, despite serious concerns about the drug’s safety and lack of efficacy, by top officials with full knowledge that the studies submitted to support its approval were fraudulent.

Several employees at told FDA officials that the liver damage associated with Ketek was known to its maker, Sanofi-Aventis, early in clinical trials but was covered up.

According to the FDA’s senior scientist, Dr David Graham, who blew the whistle on the agency’s mishandling of the Vioxx debacle, Ketek is at least as toxic to the liver as three other drugs that have been removed from the market and the FDA’s original approval of the drug was based on a study that the agency’s top officials knew was fraudulent.

Internal FDA emails that surfaced during the investigation show that at least four FDA safety officials, Dr David Graham, Dr Charles Cooper, Dr David Ross and Dr Rosemary Johann-Liang, had voiced serious concerns about the safety of the drug.

“I tried to argue that given Aventis’s track record in which they have proven themselves to be nontrustworthy that we have to consider the possibility that they are intentionally doing a poor job of collecting the postmarketing data to protect their drug sales,” Dr Cooper said in an email.

“It’s as if every principle governing the review and approval of new drugs was abandoned or suspended where telithromycin is concerned,” Dr David Graham wrote in an email that recommended Ketek’s “immediate withdrawal.”

“We don’t really know if the drug works;” he said, “no one is claiming it works better than other, safer drugs; and we’re flying blind as far as safety goes, except for our own A.D.R. data that suggests telithromycin is uniquely more toxic than most other drugs.”

In May 2006, Dr Johann-Liang called for a halt to tests of Ketek in children with ear infections, arguing that cutting the duration of ear pain by one day was hardly worth risking death.

The FDA’s actions in regard to Ketek are being investigated by Senator Charles Grassley’s (R-Iowa), Senate Finance Committee, and by Representatives, Edward Markey of Massachusetts, and Henry Waxman of California, ranking Democrats on the House Government Reform Committee.

In May 2006, the lawmakers released a statement that said although “the FDA has consistently assured the public of Ketek’s safety and efficacy, public documents obtained and examined by Representatives Markey and Waxman’s staff indicate that the approval process for this drug was seriously flawed.”

As Chairman of the Senate Committee, Senate Grassley has called for a “major overhaul and a culture change at the highest levels” of the FDA. In a May 1, 2006, press release, he noted concerns over the FDA’s complicity with the drug maker and its subsequent failure to ensure the integrity of a study on the benefits and risks of Ketek.

The Senator called it “mystifying” on May 16, 2006, that the FDA would continued to provide information that it knew was fraudulent, and warned that he planned to keep the pressure on the FDA to provide more information about Ketek’s approval and post-market surveillance.

“It’s no surprise to learn that the FDA didn’t listen to Dr. Graham on the dangers of Ketek,” Senator Grassley was quick to point out. “The FDA has made it their business to discredit Dr. Graham and others who aren’t willing to cater to the drug companies,” he noted.

In October 2001, doctors began enrolling subjects for the Ketek clinical trial known as Study 3014, and were paid $100 for each patient that signed up. The participating doctors would also receive another $150 when the study results were submitted, and a final $150 when all questions related to the study were resolved, according to the May 1, 2006, Wall Street Journal.

On July 24, 2002, drug maker Aventis submitted the results of the study to the FDA, but when FDA officials submitted the study to the advisory committee for review, they did not disclose that the Division of Scientific Investigation and Office of Criminal Investigation was investigating the integrity of the study.

The misconduct that took place during the clinical trials is so serious that critics say it calls the validity of the entire study into question. For instance, the doctor who signed up the 3rd highest number of patients, was in a chronic state of cocaine addiction while conducting the clinical trial, and was arrested and found to have cocaine hidden in his underwear, while holding his wife hostage with a gun, the same month the study results were submitted to the FDA.

Another doctor who participated in the study was totally disqualified as an investigator and prohibited from conducting any clinical trials in the future, and another who signed up 150 patients was cited for 20 violations of the study’s instructions.

Dr Anne Campbell, the doctor with the highest number of subjects in the study, was sentenced to nearly 5 years in prison in March 2004, after being charged in a 21-count indictment over her misconduct.

Senator Grassley is demanding a face-to-face interview with the FDA investigator who discovered the fraud and misconduct in the trials, who he contends “is key to understanding what the FDA did when it became clear that the safety study required by the FDA in order to approve the drug was fraudulent and faulty.”

This investigator authored a March 25, 2004, memorandum from the Division of Scientific Investigations titled, “DSI Recommendations on Data Integrity,” that states in part, that Study 3014 involved “multiple instances of fraud” and that “the integrity of data from all sites involved in [the] study … cannot be assured with any degree of confidence.”

After months of trying unsuccessfully to get an interview, Senator Grassley finally marched right over to the Department of Health and Human Services headquarters and asserted a congressional right to speak to the investigator.

After a brief conversation with senior officials, he left mad as a hornet. “This is extraordinary to me,” he said outside HHS headquarters. “I haven’t had to go to an agency like this since 1983 to get information I requested.

“I smell a cover-up,” he stated.

On June 22, 2006, Senator Grassley publicly announced a not too subtle warning to officials at the agency. “Two years ago I called a congressional hearing to probe the FDA’s handling of the withdrawn painkiller Vioxx,” he said in a statement.

“It might be time,” he warned, “to round up another oversight hearing after the runaround I got recently at the FDA.”

“The FDA,” he wrote, “refused to allow me to question an internal investigator who is leading an inquiry into alleged fraud involved with clinical trials for the antibiotic Ketek.”

“So for only the second time in 23 years,” he said, “I resurrected in June my unconventional means to fulfill my Constitutional oversight responsibilities.”

He said, “I appeared at the FDA’s doorstep,” and noted that agency officials refused to let the investigator speak to him.

However, he warned, “Bureaucratic stonewalling won’t deter this U.S. Senator.”

“I won’t rest,” Senator Grassley said, “until the light of day exposes what ought to be available for public consumption.”

“It all boils down to keeping the government accountable,” he wrote, “to the people and strengthening the public trust in government.”

In another statement released on June 29, 2006, he stated, “Ketek is another example where the F.D.A. accommodated a drug maker and turned a blind eye to serious safety concerns.”

Over the past couple of years, the suppression of the scientific process and the muzzling of scientific dissent at the FDA became evident first when officials forced Dr Andrew Mosholder to suppress a link he found between SSRI antidepressants and suicide in children, and Dr Graham went public with allegations about the FDA’s mishandling of the Vioxx matter.

On March 10, 2005, Senator Grassley gave a speech to the Consumer Federation of America and said these two whistleblowers had done more to shake up a complacent FDA than probably anybody in recent history and relayed parts of the story saying:

“Early last year I heard that the FDA was muzzling one of its own scientists. In February 2004 the FDA held a meeting to decide whether there was a link between some antidepressant drugs and suicidal behavior in kids.

“Dr. Andrew Mosholder – the FDA’s expert in this area — concluded there was a link. However, FDA management disagreed. So, when Dr. Mosholder stuck by his findings, his supervisors canceled his presentation to an advisory committee.

“Instead of allowing Dr. Mosholder to present his findings publicly and subject them to committee scrutiny, the scientific process and his peers, the FDA effectively muzzled him.”

But despite the FDA’s best efforts, Senator Grassley said, Dr Mosholder wouldn’t be silenced and months later he was proven right.

Citing information from the Department of Justice, he told the audience that there are currently under seal in the neighborhood of 100 whistleblower cases involving allegations against over 200 drug companies.

“During the past four years,” he stated, “the department recovered nearly 2 and a half billion dollars from whistleblower cases against drug companies.”

Senator Grassley called Dr Mosholder and Dr Graham great patriots. “Think about the guts it takes to undermine your career, and to go against your supervisors at a huge federal agency,” he said, “and in this case, the multi-billion-dollar drug companies.”

In an August 30, 2005, interview with Manette Loudon, the lead investigator for Dr Gary Null, Dr Graham discussed how FDA officials attempted to suppress the results of his study on Vioxx a year earlier. According to Dr Graham, prior to his Senate testimony in mid-November of 2004, there was an orchestrated campaign by senior FDA managers to intimidate him so that he would not testify about the adverse affects of Vioxx to Congress.

One attack he says, came when the acting FDA Commissioner, Lester Crawford, contacted the editor of the Lancet, a UK medical journal, and told him that Dr Graham had committed scientific misconduct and that the journal should not publish the paper that he had written showing that Vioxx increased the risks of heart attack.

The second attack came from other high level officials, he said, who contacted Senator Grassley’s office in attempt to prevent Senator Grassley from calling him as a witness.

And the third he says came from senior FDA officials who contacted Tom Devine, Dr Graham’s attorney at the Government Accountability Project, and attempted to convince him that the GAP should not represent Dr Graham because he was guilty of scientific misconduct.

According to Dr Graham, these officials posed as whistleblowers themselves, and told Mr Devine that Dr Graham was a “bully,” a “demigod,” and a “terrible person” that could not be trusted.

In one more last ditch effort to thwart Dr Graham’s testimony the week before he testified, he says, the acting Commissioner offered him a job in the Commissioner’s Office to oversee the revitalization of drug safety if he would just leave the Office of Drug Safety.

“Obviously he had been tipped off,” Dr Graham said in the interview, “by people in the Senate Finance Committee who are sympathetic to the FDA’s status quo that I was going to be called as a witness.”

To preempt his testimony, he told Ms Loudon, he was offered a job “which basically would have been exile to a fancy title with no real ability to have an impact.”

According to Dr Graham, by allowing Vioxx to stay on the market, the FDA is responsible for 140,000 heart attacks and 60,000 dead Americans. “That’s as many people as were killed in the Vietnam War,” he points out.

He says the FDA could have prevented many of the heart attacks and deaths simply by banning the high dose Vioxx back in 2000 when the agency learned about the results of the VIGOR Study. “But the FDA did nothing for almost two years,” he states. “They were “negotiating” with the company over a label.”

“The FDA made bad decisions,” Dr Graham said, “based of its culture and its institutionalized biases that favor industry, and as a result thousands of Americans died.”

During a July 18, 2005, speech on the Senate floor, Senator Grassley proclaimed, “this country’s confidence in the FDA has been shaken.”

It has not been shaken, he said, by one isolated incident or whistleblower. “It has been shaken because multiple drug safety concerns have been exposed by more than one courageous whistleblower.”

“Dr. Graham’s testimony before the Finance Committee,” he told members of Congress, “suggests that the problems are systemic.”

“Oversight of the FDA,” Senator Grassley advised, “exposed the cozy relationship that exists between the FDA and the drug industry.”

“It revealed that the FDA negotiated for almost two years with Merck,” he said, “about how to change the Vioxx label so people would know about the risk of heart attacks.”

According to Dr Graham, the Vioxx disaster would not have been as severe in the absence of direct-to-consumer advertising. “I submit,” he told Ms Loudon, “that the numbers would have been far lower than what they were.”

Due to heavy marketing of new drugs, Dr Graham says, lots of patients and doctors will use a new drug that is no better than another drug already on the market, even though the FDA does not require that new drugs be at least equivalent to, or better than, the drugs that are already there. All the drug maker has to prove is that a drug works better than a sugar pill, he says.

Silencing scientists to protect the industry has become habitual under the current politically appointed rulers of the FDA. According to Shane Ellison, author of “Health Myths Exposed,” pharmaceutically compliant politicians have “democratized” the drug industry. “This means that drug approval is a matter of 51% telling the other 49% that deadly drugs are safe and necessary,” he reports.

“Science and choice,” he warns, “no longer prevail at the FDA or at pharmaceutical companies.”

Mr Ellison is a former pharmaceutical industry chemist who says he felt a responsibility to reveal the truth about the industry’s sordid tactics after he witnessed first-hand how they deceive the public, according to a September 3, 2005, interview with Crusador Editor, Greg Ciola.

“To go against the 51% means losing your career,” Ellison said. “Therefore, the majority of scientists choose to please drug companies, not the general public.”

As an example, Mr Ellison discussed Dr Curt Furberg, a member of the FDA’s drug safety advisory committee. Dr Furberg, he says, came forward to reveal that Bextra also caused heart attack and stroke. In the British Medical Journal, Dr Furberg said that his studies showed Bextra to be no different than Vioxx, and warned that Pfizer was trying to suppress that information.

“Immediately thereafter,” Mr Ellison said, “Dr. Furberg was barred from serving on the panel that is responsible for considering the safety of cyclo-oxygenase-2 (COX 2) inhibitors.”

“The end result being more votes in favor of COX 2 inhibitors, the drug company wins by votes – not science,” Mr Ellison told Crusador.

In the case of the pain relieving Cox-2 inhibitors, the FDA’s advisory committee was stacked with experts with ties to the drug makers. Of the 32 advisers who would vote on the drugs, it has since become known that 10 of panel members had consulted in recent years for Vioxx maker, Merck, or Pfizer who made Celebrex and Bextra.

While the committee voted unanimously that all of the drugs significantly increased the risk of heart attack and stroke, in a 17-15 vote the panel said the FDA should allow Vioxx to remain on the market. A tally of the votes showed that without the 9 votes of the 10 members who consulted for the drug makers, the committee would have voted 14 to 8 to ban Vioxx.

However, the panel’s recommendation was met with scorn and outrage by medical experts and researchers alike in the media, and in a rare occurrence, the FDA went against the recommendation of its advisory panel and refused to allow Vioxx to remain on the market.

Critics also accuse the FDA of not properly monitoring the marketing activities of the pharmaceutical industry. An investigation by the House Committee on Government Reform found that since December 2001, there has been a sharp decline in enforcement actions taken against drug companies for illegally promoting their products.

The investigation determined that from 1999 to 2001, the FDA sent out 250 “Notice of Violation” or “Warning” letters to drug companies; but for the time period of 2002 through 2004, the agency sent out only 70 letters, which amounts to a reduction of more than two-thirds.

Since the Vioxx and SSRI debacles, Senator Grassley has jumped on the FDA every time there has been any indication that officials might be putting the industry’s interest over public safety. Earlier this year, he wrote a letter to the FDA saying he was concerned that it might be “dropping the regulatory ball” on stimulant drugs, prescribed to treat ADHD.

Specifically, he wrote, “I’m concerned FDA’s regulatory responsibilities haven’t kept pace with the explosion of prescriptions written to treat 2.5 million children with these drugs.”

Despite psychiatric and cardiovascular risk signals associated with the drugs, he noted, it appears the FDA has failed to promptly respond to their possible adverse effects. “Such events,” he wrote, “may include sudden unexplained deaths, strokes, cardiovascular irregularities or aggression, anxiety and depression.”

Sales of drugs, he said, “have zoomed to the moon, jumping from $759 million to $3.1 billion between 2000 and 2004.”

“And yet,” he wrote, “the FDA seems to have adopted a wait-and-see approach before charting a course of action to study these risks.”

In early February 2006, he noted, that an advisory panel had recommended adding the strongest black box warning to ADHD drugs to alert patients about the possible cardiovascular side effects.

“The recommendation,” Senator Grassley wrote, “brings even more urgency to the controversy surrounding the explosion of prescriptions being filled with these medicines.”

“As the debate unfolds,” he warned agency officials, “I will continue to closely track the FDA and urge its timely, thorough review of these drugs.”

“With millions of Americans, mostly children, regularly taking these medications,” he added, “it is essential the FDA leaves no stone unturned to investigate and review this class of drugs.”

No doubt in response to all the intense scrutiny from members of Congress, in late July 2006, the FDA outlined a series of changes it plans to make in the methods used to evaluate clinical trials. One of the proposed changes would require a drug company to notify the FDA immediately if it believes a researcher has committed fraud during a clinical trial.

As it is now, drugs companies are trusted to remove unreliable data and are not required to report any fraudulent activity to the FDA until they actually submit the application.

The agency also says it plans to clarify which adverse events in clinical trials must be reported to the review boards that monitor the studies. Other proposed change includes the standardization of forms used to collect information and a revision of the rules on how patients may qualify to participate in clinical trials.

However, people who are tempted to think that the FDA is capable of changing under the agency’s current team of politically appointed officials, had better think again.

According to an article by Russell Mokhiber and Robert Weissman, for Common Dreams on August 2, 2006, Dr Steven Nissen, chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, was recently a member of a panel debating the topic of: “Government Science Panels: Fair and Balanced?” which was moderated by National Public Radio’s Snigdha Prakash, and sponsored the Center for Science in the Public Interest.

Dr Nissen spoke about the conflict-of-interest problems “evident at the highest levels of the FDA,” the article says.

“For years,” Dr Nissen said in describing FDA leadership, “we had an interim FDA Commissioner, Lester Crawford, who shortly after confirmation, abruptly resigns, apparently because he and his wife owned stock in regulated companies.”

“Then the administration appointed Andrew Von Eschenbach as interim commissioner, creating another conflict,” he noted.

“In his role as director of the National Cancer Institute,” Dr Nissen said, “Von Eschenbach must seek FDA approval for human testing or approval of new cancer drugs, an obvious conflict.”

But even worse, he said, “the administration appointed Scott Gottlieb as deputy commissioner.”

“He came to this job with no regulatory experience, directly from Wall Street, where he served as a biotech analyst and stock promoter,” Dr Nissen stated.

“Between them,” he said, “Drs. Von Eschenbach and Gottlieb have whined incessantly about the need to speed drug development.”

“So while the American people worry about the safety of drugs,” he continued, “the top FDA leadership tells us we need faster drug approval.”

On November 12, 2005, the Boston Globe reported that prior to his job at the FDA, Dr Gottlieb worked for the PR firm of Manning Selvage & Lee and that his clients included Roche, the manufacturer of Tamiflu, and Sanofi-Aventis, the maker of Ketek, and the parent company to the nation’s sole flu vaccine maker.

According to the Globe, the Manning PR firm paid Dr Gottlieb a monthly retainer of $12,500 for nine months, for working on projects that involved eight companies. Other firms regulated by the FDA that he was involved with include Inamed Corp, a company seeking the return of silicone gel implants to the market.

Between May and July 2005, Dr Gottlieb also was paid $9,000 for consultant work performed for VaxGen, a company that won an $878 million government contract to supply the US with 75 million doses of anthrax vaccine.

In any event, no matter who’s in charge, the Senator from Iowa is keeping the heat on. In July 2006, he wrote a letter to the Daniel Levinson, the Inspector General at the Department of Health and Human Services, asking for an investigation into whether Dr Brian Harvey of the FDA, conspired against Dr Graham by providing Merck with details about Dr Graham’s presentation on Vioxx, prior to the hearing in 2004 to help the company refute his testimony.

“It is no secret that Dr. Graham was and is a critic of the FDA,” he wrote to Inspector. “However,” he said, “that does not mean the FDA should scheme with drug sponsors to discredit its own employees.”

Lawmakers Warn Drug Makers To Knock It Off After Avandia Debacle

Evelyn Pringle November 2007

On November 14, 2007, the FDA added a new black box warning to GlaxoSmithKline’s diabetes drug Avandia, about a potential increased risk of heart attacks, in addition to the black box warning that was added in August 2007, about the increased risk of heart failure.

The FDA said the new warning would also apply to Glaxo’s diabetes drugs Avandamet and Avandaryl, since they both contain the same active ingredient as Avandia.

However, Senator Chuck Grassley (R-Iowa), ranking member of the Senate Finance Committee, has asked the FDA to respond to accounts that on October 2, 2007, the agency convened a drug safety oversight board that voted to keep Avandia on the market by a one-vote margin amid considerations of a second warning.

In an October 26, 2007 letter to FDA Commissioner Andrew von Eschenbach he is also asking about the terms and conditions governing public notification with this sort of information.

“The Avandia case continues to present new rounds of questions about the way the FDA monitors and assesses drug risks and decides whether to let the public know about emerging risks,” Senator Grassley said in an October 29, 2007 press release.

Among those who voted in favor of the drug’s removal was the Department of Veterans Affairs and last month the Department announced that it was removing Avandia from its list of approved drugs and would severely limit its use. VA sales reportedly represent about 8% of total Avandia sales in the US.

On June 5, 2007, the NEJM published a paper entitled, “Rosiglitazone — Continued Uncertainty about Safety,” by Dr Jeffrey Drazen, Dr Stephen Morrissey and Dr Gregory Curfman, which drew more attention to some of the safety concerns about Avandia that were first reported in a study in the New England Journal of Medicine by Cleveland Clinic Cardiologist Dr Steven Nissen in May 2007.

The paper cited an analysis which indicated an increase of about 40% in the risk of myocardial infarction in patients receiving Avandia when compared to patients receiving either an oral diabetes drug such as metformin or a sulfonylurea or a placebo.

“Since rosiglitazone is widely used for the treatment of type 2 diabetes and since the analysis considered all publicly available data on the topic,” the authors wrote, “we published the article to make health care professionals and their patients aware of these potential adverse effects.”

On September 11, 2007, the Journal of the American Medical Association published two new studies on Avandia. One was a meta-analysis co-authored by Dr A Michael Lincoff and Dr Nissen of the Cleveland Clinic, that found Avandia’s main competitor, Actos, appeared to protect diabetic patients from heart attacks, stroke and death by 18%. The second study, also a meta-analysis, by researchers led by Dr Sonal Singh at Wake Forest University, concluded that Avandia increased the risk of heart attack by 42%.

According to the November 2007 report by the Senate Finance Committee, FDA scientists presented an analysis at a July 30, 2007, safety panel meeting, which estimated that Avandia caused approximately 83,000 excess heart attacks since coming on the market.

The report notes that Dr John Buse, a medical researcher at the University of North Carolina, tried to sound the alarm about the increased risks associated with Avandia in 1999, and states: “Had GSK considered Avandia’s increased cardiovascular risk more seriously when the issue was first raised in 1999 by Dr. Buse, instead of trying to smother an independent medical opinion, some of these heart attacks may have been avoided.”

The committee found it most troubling that the plans to silence Dr Buse involved discussions by GSK executives at the highest levels, including CEO Jean-Pierre Garnier.

Citing relevant e-mails, the report says, “GSK executives labeled Dr. Buse a ‘renegade’ and silenced his concerns about Avandia by complaining to his superiors and threatening a lawsuit.”

GSK also required Dr Buse to sign a letter claiming that he was no longer worried about cardiovascular risks associated with Avandia, which GSK officials referred to as Dr Buse’s “retraction letter,” and intended to use the letter to gain favor with a financial consulting firm that was evaluating GSK’s products for investors, according to the report.

However, even though Dr Buse remained silent in public, he continued privately to voice his concerns about the problems with Avandia and wrote a letter to FDA Commissioner Dr Jane Henney on March 15, 2000, after he signed the retraction letter, warning the FDA about the risks of Avandia and describing GSK’s abuse of clinical trial data.

“I remain concerned about the safety of rosiglitazone,” he wrote, “in light of its consistent negative impact on lipids documented in the FDA registration data as well as a worrisome trend in cardiovascular deaths and severe adverse events in the subjects exposed to rosiglitazone versus active comparators.”

Dr Buse also stated, “I think the FDA has to act forcefully to prevent the rampant abuse of clinical trial data by SmithKline Beecham.”

He warned Dr Henney that Glaxo was overstating the safety of Avandia with respect to cardiovascular risks. “I have been shown glossy materials claiming that rosiglitazone has been uniquely studied in patients with preexisting cardiac disease,” he wrote, “including patients with a number of associated conditions (such as unstable angina).”

“I know for a fact,” he wrote, “that such patients are excluded in clinical trials as I am a PI in one of their trials.”

“I am sure there have been abuses by representatives of all companies that market drugs,” Dr Buse stated, “but there is something pervasive and systematic that I detect in my travels regarding the marketing of rosiglitazone.”

The following month, GSK officials somehow obtained a copy of his letter to the FDA, and GSK drafted another letter to Dr Buse from executive Martin Freed stating: “I remain concerned about your ongoing aggressive posture towards rosiglitazone and SmithKline Beecham. In my opinion, you have presented to [FDA] several unfair, unbalanced, and unsubstantiated allegations.”

The Senate report notes that Dr Buse remained silent for about two years, but on October 23, 2005, he again privately voiced his opinion about Avandia in an e-mail to Dr Nissen and described his treatment by GSK. Specifically, Dr Buse wrote:

“Steve: Wow! Great job on the muriglitazar article. I did a similar analysis of the data at rosiglitazone’s initial FDA approval based on the slides that were presented at the FDA hearings and found a similar association of increased severe CVD events. I presented it at the Endocrine Society and ADA meetings that summer. Immediately the company’s leadership contact[ed] my chairman and a short and ugly set of interchanges occurred over a period of about a week ending in my having to sign some legal document in which I agreed not to discuss this issue further in public.”

Later in the email, Dr Buse wrote, “I was certainly intimidated by them but frankly did not have the granularity of data that you had and decided that it was not worth it.”

“Again congratulations on that very important piece of work,” he stated. “It makes me embarrassed to have caved in several years ago.”

The report also describes GSK’s behavior since the Committee first brought the allegations about Avandia to light as “less than stellar.”

“Instead of acknowledging the misdeed to investors, apologizing to patients, and pledging to change corporate behavior,” the report notes, “GSK launched a public relations campaign of denial.”

Specifically, the report quotes a May 21, 2007, company press release entitled, “GSK Response to US Senate Committee on Finance,” which states that the allegations raised by the Committee were “absolutely false,” and a July 25, 2007 interview in The Philadelphia Inquirer in which CEO Jean-Pierre Garnier denied having any knowledge of the intimidation of Dr Buse.

The report also says the behavior of GSK during the time that Dr Buse voiced concerns was “less than stellar.” Had Dr Buse been able to continue voicing his concerns, without being characterized as a “renegade” and without the need to sign a “retraction letter,” it appears that the public good would have been better served.

The report notes serious concerns about the culture of leadership at GSK, but, even “more serious perhaps is our fear that the situation with Dr Buse is part of a more troubling pattern of behavior by pharmaceutical executives,” the Committee states.

As an example, the report points out that Dr Gurkirpal Singh of Stanford University also testified at a Committee hearing in 2004 that an executive at Merck sought to intimidate him by calling his superiors and warned him that they would make life very difficult for him if he persisted in his request for data on Vioxx.

“Merck’s intimidation of Dr. Singh as it sought to protect Vioxx,” the report says, “bears striking similarities to apparent threats by GSK against Dr. Buse to protect Avandia.”

During his November 15, 2007 speech on the Senate floor, Senator Grassley discussed the hearing on November 18, 2004, that followed the withdrawal of Vioxx, which “turned the spotlight on systematic problems” at the FDA.

“We found that the FDA maintained a cozy relationship with the drug industry and suppressed scientific dissent regarding agency actions on drug-safety,” he said.

At that Vioxx hearing, Senator Grassley said the Committee heard about Merck using its power, influence and access to discredit FDA safety expert Dr David Graham and how Merck also tried to intimidate Stanford researcher Dr Gurkirpal Singh and warned him to stop asking for more safety data on Vioxx, despite the fact he was their consultant.

He called it “troubling” that three years later, “I am here with my colleague, Senator Baucus, to talk about another case where pharmaceutical executives used power, influence, and access to intimidate a medical researcher.”

In essence, he said, another company wanted to put an end to another scientist who was voicing concerns about the cardiovascular risks associated with a drug. “So what we have here, are three cases where companies intimidated researchers who dared to express concerns about risky drugs,” he pointed out.

The Committee’s report also notes concern that this behavior may be more prevalent than evidenced in these two cases. “Corporate intimidation, the silencing of scientific dissent, and the suppression of scientific views threaten both the public well-being and the financial health of the federal government, which pays for health care,” the report states.

Ending FDA’s Love Affair With Big Pharma

Evelyn Pringle November 2006

With the Democrats back in power, critics say officials at the FDA and representatives of Big Pharma had better plan on spending much of their time testifying on Capital Hill in Congressional hearings in 2007.

Democrats have spelled out their plans to change how the administration chooses experts to sit on FDA advisory panels and put an end to the suppression of dissenting opinions of FDA scientists.

These panels advise the agency on which drugs should be approved, what their warning labels should say, and how clinical studies should be conducted. The approximately 300 so-called experts make decisions that potentially affect billions of dollars in sales for Big Pharma and the FDA follows their recommendations almost exclusively.

Critics are demanding stricter conflict of interest rules for members of the panels and a November 17, 2006, session of the Senate Committee on Health, Education, Labor, and Pensions, gave the Democrats their first opportunity to indicate how they will deal with the out of control FDA once they become the majority in Congress next year.

The hearing titled, “Building a 21st Century FDA: Proposals to Improve Drug Safety and Innovation,” was held to push forward FDA reform legislation Senate Bill 3807, the “Enhancing Drug Safe and Innovation Act of 2006,” previously introduced by outgoing committee chairman, Senator Michael Enzi (R-WY), together with incoming chairman, Senator Edward Kennedy (D-MA). The two Senators began working on the bill when Vioxx was pulled from the market after it was found to cause heart attacks and strokes.

Cleveland Clinic physician-scientist, Dr Steven Nissen, MD, who has served as an expert on FDA advisory panels, testified at the hearing and described “a crisis in public confidence in the FDA following an unprecedented series of revelations about drug and device safety” and referred to the Senate reform bill as a “major step forward.”

“I am a strong supporter of this bipartisan effort to enhance the FDA’s effectiveness and improve drug and device safety,” he said. “I believe that this legislation represents the best chance we have had in a long time to make a real difference for patients in this challenging area.”

Dr Nissen said new laws are needed to strengthen the authority of the FDA. “Currently,” he explained, “the Agency must “negotiate” with industry to make even simple changes in drug labels.”

“I served on a 2001 Advisory Panel that recommended a warning label for Vioxx,” he informed the panel, “but it took 14 months before the FDA could secure agreement from the company to accept a weakly written warning.”

As for enacting new conflicts of interest rules for advisory panels, Dr Nissen testified that improvements “in the Advisory Committee process will help to ensure that FDA consultants are less likely to be influenced by financial conflicts of interest.”

Merrill Goozner, Director of Integrity in Science Center for Science in the Public Interest, testified about the blatant conflicts of interest involving the expert panel that reviewed Vioxx and the other COX-2 inhibitors, and how the panel concluded that Vioxx was safe enough to stay on the market, even though Merck had already removed it from the market.

Mr Goozner told the Senate committee that ten of the 32 scientists on the panel had financial ties to the drugs’ makers. “Had their votes been eliminated,” he said, “two of the drugs in the class would have been voted down by the panel.”

“The best way to solve all these problems,” Mr Goozner stated, “without undermining the quality of the advice offered to the FDA – is to completely eliminate conflicts of interest from these committees.”

Jim Guest, president and CEO of Consumers Union, publisher of Consumer Reports, testified that improvements are needed to help prevent future drug safety disasters and called for a rule specifying that at least 90% of the members on advisory committees who decide whether a drug should be approved be free of conflicts of interest from the pharmaceutical industry.

In “the wake of the Vioxx and Paxil disasters,” he told the committee, where tens of thousands of Americans needlessly suffered, we’ve educated our more than 20 million readers on the need for stronger state and Federal drug safety laws.

During his testimony, Mr Guest pointed out that GlaxoSmithKline had concealed the results of clinical trials linking Paxil to an increased risk in suicidality among adolescents, as proven, he noted, by New York Attorney General, Eliot Spitzer’s successful lawsuit against Glaxo.

Furthermore, he told the committee, the hidden trials also revealed that Paxil was actually less effective than placebos among adolescents.

Mr Guest also told the committee that these abuses by drug companies have not ended. As recently as September 29, 2006, he noted, the FDA released a Public Health Advisory that said Bayer, maker of Trasylol, failed to inform an advisory committee during a hearing held 8 days earlier to discuss Trasylol, of a new study that revealed an increased risk of death, serious kidney damage, congestive heart failure and stroke.

In addition, Mr Guest described problems created by fraud and falsification of studies used in the drug approval process. “In the recent case of Ketek,” told the panel, “the FDA found multiple instances of fraud in the company’s clinical trial of about 24,000 patients, some cases of which the maker Sanofi already knew about yet failed to notify the agency.”

Internal FDA emails that surfaced during a previous Congressional investigation revealed that the FDA was aware of the dangers with the drug and that at least four FDA safety officials, Dr David Graham, Dr Charles Cooper, Dr David Ross and Dr Rosemary Johann-Liang, had voiced serious concerns about the safety of Ketek (telithromycin).

“It’s as if every principle governing the review and approval of new drugs was abandoned or suspended where telithromycin is concerned,” Dr Graham wrote in an email calling for “immediate withdrawal,” of Ketek.

On the Republican side of the isle, the Democrats have a strong ally in Senate Finance Committee chairman, Senator Chuck Grassley (R-Iowa), who also has been one of the FDA’s most out-spoken critics since the Vioxx and SSRI disasters.

His latest focus has been on the FDA’s handling of the Ketek debacle. In a May 1, 2006 press release, Senator Grassley expressed concerns over the FDA’s complicity with the drug company and its subsequent failure to ensure the integrity of a study on the benefits and risks of Ketek. In another statement released on June 29, 2006, he said, “Ketek is another example where the F.D.A. accommodated a drug maker and turned a blind eye to serious safety concerns.”

Critics say the worst conflicts of interest within the FDA are the result of major Big Pharma influence over the Bush appointed officials at the top.

According to Robert Brava-Partain, an associate attorney at the national law firm of Baum Hedlund, the FDA has become an “approval factory” for drugs that are ineffective and dangerous. “This factory is manned by doctors who, in any other setting,” he says, “would have irreconcilable conflicts of interest with the companies the agency is supposed to be monitoring.”

And at the top of the factory, he says are, “political appointees who make no apologies for engaging in promanufacturer advocacy.”

On November 12, 2005, the Boston Globe reported that prior to his job at the FDA, Deputy Commissioner of Medical and Scientific Affairs, Dr Scott Gottlieb worked for the PR firm of Manning Selvage & Lee and that his clients included Ketek maker Sanofi-Aventis, which is also the parent company to the nation’s sole flu vaccine maker, and Roche, maker of Tamiflu.

According to the Globe, Manning paid Dr Gottlieb a monthly retainer of $12,500 for nine months for work involving 8 companies, and he was also paid $9,000 for consultant work for VaxGen, a company that won an $878 million government contract to supply the US with 75 million doses of anthrax vaccine.

Dr Gottlieb and Dr Nissen recently went head to head when they both participated in a debate on the topic: “Government Science Panels: Fair and Balanced?” moderated by National Public Radio’s Snigdha Prakash, and sponsored the Center for Science in the Public Interest, reported on August 2, 2006, by Russell Mokhiber and Robert Weissman, in Common Dreams.

To his credit, Dr Nissen can never be called a back-stabber because while sitting next to fellow panelist, Dr Gottlieb himself, Dr Nissen very candidly described the conflicts of interest which he described as “evident at the highest levels of the FDA.”

“For years,” he said of the FDA leadership, “we had an interim FDA Commissioner, Lester Crawford, who shortly after confirmation, abruptly resigns, apparently because he and his wife owned stock in regulated companies.”

“Then the administration appointed Andrew Von Eschenbach as interim commissioner,” he noted, “creating another conflict.”

“In his role as director of the National Cancer Institute,” Dr Nissen said, “Von Eschenbach must seek FDA approval for human testing or approval of new cancer drugs, an obvious conflict.”

But even worse, after that, Dr Nissen stated, “the administration appointed Scott Gottlieb as deputy commissioner.”

“He came to this job with no regulatory experience, directly from Wall Street, where he served as a biotech analyst and stock promoter,” Dr Nissen told the audience.

Dr Gottlieb’s reply to Dr Nissen’s remarks, was basically that he would not dignify the comments with a response.

This month, Dr Gottlieb presented an early Xmas gift to one of his former employers, Inamed Corp, when the FDA announced that it would lift restrictions on the sale of silicone gel breast implants on November 17, 2006.

Firms that Dr Gottlieb was involved with prior to his gig at the FDA, according to the Boston Globe, include “Inamed Corp., one of two companies seeking to return silicone gel implants to the market.”

As for the last FDA commissioner, 2 months after Mr Crawford was confirmed, MSNBC announced: “Embattled Food and Drug Administration Commissioner Lester Crawford abruptly resigned Friday, telling his staff that at age 67 it was time to step aside.”

In a resignation letter to Bush on September 23, 2005, Mr Crawford said his resignation was “effective immediately.”

On October 26, 2005, the Wall Street Journal stated: “As late as 2004, former Food and Drug Administration head Lester Crawford or his wife owned stock in companies that make or distribute products regulated by the agency.”

Six months later, on April 29, 2006, the New York Times reported that Mr Crawford, was under criminal investigation by a federal grand jury over allegations of financial improprieties and false statements to Congress, quoting his lawyer, Barbara Van Gelder.

On October 16, 2006, the Associated Press said that Mr Crawford had agreed to plead guilty to charges of failing to disclose a financial interest in firms regulated by his agency. “The Justice Department accused the former head of the Food and Drug Administration in court papers,” the article stated, “of falsely reporting that he had sold stock in companies when he continued holding shares in the firms governed by FDA rules.”

After leaving the FDA, Mr Crawford quickly moved on to a job with a firm called Policy Directions, Inc. A few of the firm’s accomplishments for clients listed on its Web site are: (1) achieved FDA advisory committee support for a product that had originally been voted down; (2) Interceded with FDA when the agency failed to provide final approval for client’s product because it had granted orphan drug status for a product by another company and client’s product was approved; (3) created a coalition of six biotechnology firms to promote legislation advantageous to client and meet with agency officials to prevent onerous rulemaking; (4) wrote industry-coalition draft of legislative authority for a regulatory agency that was included in final bill; (5) created and led coalition of universities, research institutions, pharmaceutical and biotechnology companies to lobby Congress to stop a federal agency from costly and ineffective rulemaking; and (6) led an industry coalition that stopped several negative amendments to agriculture/FDA appropriations bills.

On its Web site, the firm also states, “PDI has longstanding relationships with key personal and committee staffs in Congress, as well as with critical players at important agencies within the Administration.”

That appears to be an understatement since Mr Crawford joined the company. The firm should put modesty aside and inform potential clients that it now has inside information about the status of each and every drug, device, and company regulated by the FDA.

Although Mr Von Eschenbach has served as acting commissioner since Mr Crawford left in disgrace, critics say the likelihood of his confirmation as the permanent commissioner is not a done deal, especially now that Senator Grassley is protesting his confirmation and became the third Republican to join the campaign to block the nomination.

As for the Senator’s reasons, it seems that Mr Von Eschenbach has refused to cooperate with Senator Grassley’s investigation into the FDA’s approval of Ketek and has refused requests for agency documents and interviews with FDA staff, even after subpoenas were issued, according to a November 16, 2006 letter that Senator Grassley sent to Senate Majority Leader Bill Frist (R-TN).

“I am extremely disturbed,” Senator Grassley wrote, “by the Acting Commissioner’s continued failure to comply with the committee’s subpoenas over the past six months.”

There are three major FDA advisory committee meetings scheduled for December, 2006 to review: drug-eluting stents on December 7-8; SSRI use and adult suicidality on December 13; and Ketek on December 14-15.

But it does not appear that the FDA is too worried about improving the public image of the advisory panels because reports from persons wanting to speak at the SSRI hearing say the FDA is refusing to allow enough time for public comments and is refusing to release the complete list of names for members of the panel until the day before the hearing making it impossible to determine whether they have financial ties to SSRI makers.

Lawmakers Go After Thugs at FDA Over Avandia

Evelyn Pringle June 2007

In one of the latest developments in the Avandia diabetes drug saga, on June 7, 2007, a bipartisan group of powerful lawmakers sent a letter to FDA asking Commissioner Andrew von Eschenbach asking for an explanation of the agency’s policy on conflicts of interest regarding hiring employees directly from drug companies regulated by the FDA.

At the center of the controversy, is the conduct of FDA spokesman, Douglas Arbesfeld, who has worked for several drug companies, in sending emails to journalists in what the lawmakers refer to as “smear campaigns” against cardiologist, Dr Steven Nissen, Chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, who recently waved the red flag about the risks associated with GlaxoSmithKline’s Avandia.

Dr Nissen and Kathy Wolski, MPH, a statistician, evaluated the 42 studies involving nearly 28,000 patients and compared the 15,560 patients who were using Avandia to the patients who were not using the drug and found there were 86 myocardial infarctions in the Avandia group and 72 in the control group and there were 39 deaths from cardiovascular causes in Avandia patients compared to 22 in the control group.

“Cardiovascular disease is far and away the leading cause of death in diabetes,” Dr Nissen said in the May 23, 2007 Wall Street Journal. “If you find a diabetes drug increases the risk of heart attacks,” he warned, “the consequences are so grave that it warrants urgent action.”

The June 7, 2007 letter to the FDA is signed by Senators Chuck Grassley, Max Baucus and Sherrod Brown, as well as Representatives John Dingell and Bart Stupak and they want a response to their inquiry by June 20, 2007.

At a June 6, 2007, hearing before the US House Committee on Oversight and Government Reform, Commissioner von Eschenbach testified that Arbesfeld had been formally reprimanded with a letter in his employment file but apparently the lawmakers believe his conduct warrants more than a slap on the wrist.

“We are concerned that Mr. Arbesfeld sent this message using his Government e-mail,” the lawmaker’s letter states, “which carried his FDA signature line and work-related contact information at the bottom.”

“In several news articles on other matters,” it says, “Mr. Arbesfeld is named as the spokesman for FDA.”

“Given that he has acted in this capacity in the past,” the lawmakers wrote, “this e-mail may have given journalists the impression that the United States Government actively encourages smear campaigns against independent scientists.”

“The Committee finds it even more troubling that Mr. Arbesfeld may be using his position
with FDA to settle old scores with Dr. Nissen,” the letters states.

“Certainly, Mr. Arbesfeld is familiar with Dr. Nissen, since the two have been on opposing sides of drug safety in the past,” the lawmakers wrote.

The letter cites an April 26, 2005, New York Times article that reported quotes from Dr Nissen that were critical of Natrecor, a drug made by Johnson & Johnson

The Times noted that Dr Nissen cast the only vote against Natrecor when a FDA advisory panel recommended its approval in 2001, and the person defending Natrecor in the article was Mr Arbesfeld, as a spokesman for J&J at the time.

The lawmakers called Mr Aresfeld’s emails to journalists, “a completely unacceptable use of Government time and equipment.”

“In the Agency’s response to this incident,” the letter said, “it stated that Mr. Arbesfeld is a consultant and does not speak on behalf of FDA.”

“Accordingly,” the lawmakers pointed out, “this response may leave the media wondering how they should interpret future e-mails from FDA spokesmen and Mr. Arbesfeld, in particular.”

In a June 7, 2007 press release announcing the letter, Senator Max Baucus stated, “I have some serious questions about Mr. Arbesfeld’s use of government resources, but I am even more concerned about whether his drug company connections led him, in any way, to seek to unjustly discredit Dr. Nissen.”

“The FDA’s ultimate duty is to ensure the safety of the products it regulates,” he added, “which includes sharing credible, potentially life-saving information from any trustworthy source.”

In summary, the lawmakers want answers the following: (1) What is the justification for use of taxpayer dollars for a communications consultant? (2) What is FDA’s policy regarding the hiring employees who recently worked for the companies directly regulated by the Agency? (3) How does FDA ensure that consultants do not have relationships with companies in direct conflict with his role as FDA spokesperson? (4) Is Arbesfeld currently receiving, or has he received in the last year, income or other remuneration from companies directly regulated by FDA? (5) Does FDA have a policy regarding employees using their official e-mail accounts to express their personal opinions, which may not be FDA positions, to members of the press? (6) If there is such a policy, what is that policy?

Senator Grassley and the Senate Finance Committee is also investigating a matter involving the mistreatment by top FDA officials of Dr Rosemary Johann-Liang, the Deputy Director of the FDA’s Division of Drug Risk Evaluation (DDRE), who was rebuked in March 2006, after she approved a recommendation by an FDA safety reviewer that the labels of both diabetes drugs, Avandia and Actos, should carry additional warnings.

On June 4, 2007, the Committee sent the FDA Commissioner a letter demanding a response to questions related to this matter by June 20, 2007.

In the letter, Senator Grassley cited an internal FDA memorandum, obtained by his Committee, dated February 22, 2006 that was prepared he said, by “a very seasoned safety evaluator” in the DDRE, that made several recommendations including that Glaxo should include macular edema, a condition that involves swelling of the retina and can cause blindness, as a “serious adverse event” on Avandia’s label.

The memo also recommended that congestive heart failure be highlighted in a box warning. CHF is a condition where fluid builds up in the lungs causing severe shortness of breath and potential death and requires immediate attention.

To support the recommendation for a black box warning, the February 22, 2006 memo specifically quoted the FDA regulation that states in part that “…special problems, particularly those that may lead to death or serious injury, may be required by the Food and Drug Administration to be placed in a prominently displayed box….”

Senator Grassley called the fact that the FDA had not yet acted on the recommendations troubling. “But another allegation,” he wrote, “has come to the Committee’s attention that is simply unconscionable.”

It has been alleged by multiple sources, he said, both in and out of the FDA, that the Deputy Director was reprimanded verbally for signing off on the memorandum.

“I also was informed,” he wrote, “that the DDRE Deputy Director was advised that she would no longer be able to “sign off” on any matters related to Avandia in the future.”

He also noted that she was told that, “in the future, she could no longer sign off on any recommendations for major regulatory actions, like box warnings, without first checking with the DDRE Director.”

“I also sincerely hope that this is not standard practice within the FDA,” Senator Grassley wrote. “Those FDA employees dedicated to post-marketing surveillance at the FDA should be able to express their opinions in writing and independently without fear of retaliation, reprimand, or reprisal,” he said.

Post-marketing surveillance is critical to the health of this nation, he advised.

Glaxo Stuck in Damage Control Over Avandia

Evelyn Pringle June 5, 2007

On May 23, 2007, the Associated Press reported that more than 6 million people worldwide have taken Avandia (rosiglitazone), made by GlaxoSmithKline, to control blood sugar since it came on the market in 1999, and about 1 million patients in the US currently use the drug.

However, studies recently analyzed at the Cleveland Clinic shows Avandia users could have up to a 43% increased risk of heart attack and a 64% likelihood of an increase in heart- related disease.

On June 1, 2007, MedPage Today reported that doctors responding to an online survey “overwhelmingly rejected” the idea of prescribing Avandia for new patients with diabetes.

More than 200 participants completed the survey and 72% voted no to the question of whether they would start patients on rosiglitazone in view of the published report in the New England Journal of Medicine by cardiologist, by Dr Steven Nissen of the Cleveland Clinic, linking the drug to a 43% increase in the relative risk of myocardial infarction among those with diabetes.

Since the NEJM report was released online on May 21, 2007 Glaxo shares have declined 12% losing $19.7 billion of the firm’s market value.

According to reporter Andrea Gerlin for Bloomberg News on June 1, 2007, Glaxo was the pharmaceutical industry’s top advertiser last year, in promoting its diabetes and asthma treatments to patients and doctors.

Bloomberg reports that Glaxo spent $849 million on consumer advertising last year, citing information from Nielsen Monitor Plus, a unit of New York-based Nielsen Media Research.

In return, Avandia generated $3 billion in sales for Glaxo in 2006, or 7% of the company’s total sales, Bloomberg says.

“Glaxo knew its Avandia diabetes pill posed a risk for heart and circulatory complications as early as 1999,” the article states, “when the medicine won U.S. approval.”

In an interview with Bloomberg on May 23, 2007, Dr Nissen said, “I just built this piece by piece until I had enough.”

Until he found the Glaxo study that is. “Then I stumble upon the company’s own meta analysis,” he said, “deeply buried on their Web site, and it shows the same thing.”

“It was a eureka moment for sure,” he told Bloomberg.

Early last month Dr Nissen, chair of cardiovascular medicine at the Cleveland Clinic and immediate past president of the American College of Cardiology, was named one of the 100 Most Influential People by Time magazine.

In the magazine, best-selling author and cardiologist, Dr Mehmet Oz, described Dr Nissen as “a health crusader who devotes his time equally to developing medical protocols that can keep people well and exposing ones that don’t.”

In a May 3, 2007 interview with Heartwire, Dr Nissen said he can freely speak out on issues because “I have had fantastic support from the Cleveland Clinic to be able to say what I really think.”

“I do take very clear positions on public issues,” he acknowledged, “everything from stent safety to FDA reform.”

But he’s always had the support, he told Heartwire, “of an organization that said to me, ‘Tell it the way you see it and we’ll support you.'”

“Not everybody works at a place like that,” he added.

However, it appears that the FDA is now on the attack against the man honored by Time Magazine last month. On May 30, 2007, Dr Nissen showed ABC News an e-mail sent to several health reporters by Douglas Arbesfeld, a senior communications consultant to the FDA and former spokesman for Johnson & Johnson.

In the e-mail, entitled “What are St. Steven’s feet made of? Clay, perhaps?,” Mr Arbesfeld forwarded a critical news article which included an anonymous blogger accusing Dr Nissen of playing favorites among drug companies.

Mr Arbesfeld included a comment on a blog posting, originally published in the Wall Street Journal, that accuses Dr Nissen of being critical of companies that do not support drug trials conducted at the Cleveland Clinic: “Wake up, pharmaceutical companies … if you don’t hire the Cleveland Clinic for your big trials then you face the firing squad from Nissen and Company,” it said.

Dr Nissen is more than a little upset. “I’m a pretty tough guy,” he told ABC News, “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.”

“Using taxpayer dollars,” he pointed out, “a federal agency’s press office, rather than responding to the scientific questions that I raised, attempting to smear me individually” is unacceptable.

FDA quickly tried to deny responsibility for the conduct of its spokesperson. In a statement to ABC News, the FDA said: “The content of the e-mail from an FDA consultant was his own words and does not represent an FDA position.”

Dr Nissen told ABC News that he is even more infuriated that instead of addressing the Avandia study itself, a top FDA spokesman would distribute articles including the blog disparaging his reputation and that of the Cleveland Clinic.

“They’re barking up the wrong tree,” Dr Nissen told ABC. “While I did spend a sleepless night about this,” he said, “I’m not backing down.”

“What counts here is the health of our patients,” he said. “And if they think they can intimidate me by doing this … they have another thing coming.”

Glaxo’s got plenty to worry about, but right about now using the FDA to defame reputable scientists is not a good idea. The FDA has its own Avandia troubles with both Houses of Congress demanding to know what the agency knew, when it knew it and why the FDA did not protect consumers from this new Vioxx-like disaster.

Last month, the FDA announced that it would form an advisory panel in response to a NEJM report. On May 25, 2007, a coalition of scientific, public health and consumer organizations issued a letter to the FDA asking for the exclusion of any scientists with financial ties to Glaxo

“In light of this study, and faltering public faith in the integrity of the FDA drug approval process,” the letter said, “we write to urge you to ensure that the composition of any advisory committee that is being convened to review the safety of Avandia be free of any conflict of interest.”

“At the minimum,” the Group wrote, “no member of this committee should have had any financial ties to GlaxoSmithKline, Avandia’s maker, for the past 36 months.”

Glaxo will probably be stuck in damage control mode for quite awhile. On May 21, 2007, the day the NEJM report was made pubic, Morgan Stanley analysts led by Andrew Baum warned in a note that Avandia is facing new competition and reports of a heart risk may lower sales by as much as 50%. Glaxo’s “robust defense of Avandia safety and their conduct comes with a high risk if evidence of poor disclosure subsequently emerges,” Mr Baum wrote.

FDA Avandia Mole Defends Off Label Marketing of Natrecor

Evelyn Pringle August 12, 2007

It looks like that Mafia guy, Dr Steven Nissen, leader of the Cleveland Clinic gang, who blew the whistle on the diabetes drug Avandia and before that Vioxx, was on to something when he voted against the FDA’s approval of the heart failure drug Natrecor in 2001.

Giving once- or twice-weekly outpatient injections of Natrecor does not reduce the risk of death or hospitalization for heart or kidney problems, according to research presented at the American College of Cardiology meeting in New Orleans in March 2007.

In fact, the study of 920 patients found that outpatient use of Natrecor provided absolutely no benefit. The finding should halt the practice of giving once- or twice-weekly Natrecor to outpatients, said researcher Dr Clyde Yancy, medical director of the Baylor Heart and Vascular Institute in Dallas, Health Day reported on March 26, 2007.

Of course, the revelation that Dr Nissen was running the Cleveland Clinic Mafia and that they were out to get GlaxoSmithKline by publishing a study that showed Avandia increased the risk of heart attacks and deaths came in an email to reporters from FDA spokesman Douglas Arbesfeld, which included the warning to other drug companies, “if you don’t hire the Cleveland Clinic for your big trials then you face the firing squad from Nissen and Company.”

Mr Arbesfeld left his position as a highly-paid spokesperson for Johnson & Johnson to become a dedicated public servant at the FDA, if his supporters are to be believed.

When his conduct of sending the email came under scrutiny, Peter Pitts, who co-authored a June 6, 2007, critical commentary in the Washington Times about the Avandia study and fondly referred to Dr Nissen as a “Patron Saint of Drug Safety” and “Saint Steven the Pure,” put out a statement on the internet saying that, by sending the email, Mr Arbesfeld was just defending the FDA and praised his selfless work, stating:

“I know Doug Arbesfeld,” he wrote, “and he is a guy devoted to advancing the public health,” he wrote.

“He is also a guy who took a pretty significant pay cut to put in some time in public service,” Mr Pitts pointed out.

In response to that assertion, it could certainly be argued that a mole at the FDA would be in a position to earn far more money by selling invaluable insider information to all the drug companies than as media person working for one company.

It should be noted that in his email to reporters, Mr Arbesfeld also referred to Dr Nissen as St Steven – surely just by coincidence.

For the record, the Cleveland Clinic is rated as the top cardiac center in the country by US News and World Report, and Dr Nissen holds the number 72 position on Time Magazine’s list of the 100 most influential people in our world.

An effort that included at least 50 different google searches on the internet over a period of several days found no similar praise listed for Mr Arbesfeld other than Mr Pitts’ recent two-liner that showed up on about every search.

At the end of his Times commentary, Mr Pitts listed himself as the president of the Center for Medicine in the Public Interest and a former FDA associate commissioner, but a little checking revealed that he is also a Senior Vice President at the public relations firm of Manning, Selvage & Lee.

A review of the Manning website shows that the firm’s clients have included Pfizer, Eli Lilly, AstraZeneca, Sanofi-Aventis, Johnson & Johnson, Genentech, Novartis, Amgen and Hoffmann La-Roche.

A review of Mr Pitts’ articles on the internet clearly shows that he is in lockstep with his industry clients against: (1) allowing Americans to import drugs from other countries to cut costs; (2) allowing the government to negotiate lower drug prices; (3) barring drug makers from promoting their drugs for uses not approved by the FDA; (4) cutting back on direct-to-consumer advertising, and (5) adding black box warnings to product labels.

As luck would have it, a bit more checking found a December 16, 1999, press release by the Healthcare Marketing & Communications Council which reported that Mr Arbesfeld had joined Manning, Selvage & Lee as Senior Vice President.

The list of pharmaceutical companies that Mr Arbesfeld has worked for over the years includes Ciba-Geigy in 1994, and Rhone Poulenc Rorer Pharmaceuticals in 1998, the same year the company announced that it would merge with Hoechst AG to become Aventis, which merged with Sanofi-Synthelabo in 2004 to become Sanofi-Aventis.

In 1999, Mr Arbesfeld would have been working for the Manning clients listed above, and on August 5, 2002, he identified himself to Reuters as promoting a prescription drug card program called “Together Rx” for 7 drug companies that included Bristol-Myers, Aventis, GlaxoSmithKline, Johnson & Johnson, AstraZeneca, Abbott Laboratories and Novartis.

Finally, Mr Arbesfeld is listed as the contact person for Johnson and Johnson subsidiaries Janssen Pharmaceutica, Ortho-McNeil Pharmaceutical and Ortho Biotech Products in the 2005 Reporters Handbook.

While his supporters say Mr Arbesfeld’s email to reporters was justified, lawmakers on Capitol Hill see it differently and have launched an investigation into what they refer to as a smear campaign against Dr Nissen. At a June 6, 2007, hearing before the US House Oversight Government Reform Committee, in response to questions about Mr Arbesfeld email stunt, FDA Commissioner Andrew von Eschenbach claimed that he did not approve of the email and told the lawmakers, “I completely concur with you that it was inappropriate and unacceptable.”

“It was an inappropriate and unfortunate act on the part of an individual,” he said, “which has been addressed through disciplinary procedures.”

In a letter to the FDA Commissioner, the lawmakers said they found it troubling that Mr Arbesfeld might be trying to settle old scores with Dr Nissen because he cast the lone vote against the approval of the heart drug Natrecor (nesiritide) and later spoke out against the off-label use of the drug in a New York Times article in which Mr Arbesfeld spoke on behalf of the drug’s maker J&J subsidiary Scios.

The fact is, a review of the regulatory history behind Natrecor proves that Dr Nissen was right then, just as he is now about Avandia.

The drug was approved for limited use by hospitalized patients with acute congestive heart failure, to be administered intravenously under close supervision. However, due to a massive off-label marketing campaign, the drug was soon being administered in outpatient settings at a much greater dose and for longer periods of time than recommended.

In May 2005, the New York Times reported that tens of thousands of patients were undergoing “tune-ups” at outpatient clinics by receiving weekly infusions of Natrecor over a period of months.

In the July 14, 2005, New England Journal of Medicine, apparently another Mafia guy from the Cleveland Clinic gang, Dr Eric Topol, was out to get J&J because he reported that the company was encouraging physicians to open their own infusion centers to bill Medicare for Natrecor treatment and that company documents instructed doctors to bill Medicare $408 for eight hours of observation during the infusion, above and beyond the actual cost of the drug, which was around $500 per vial, he said.

In addition, the company set up a toll-free telephone hotline for “Natrecor Reimbursement Support” and published a 46-page reimbursement and billing guide to provide doctors with specific Medicare billing codes.

“Natrecor was never shown to be superior for reducing death or reducing the need for repeat hospitalizations,” Dr Topol said, and asked: “How could this happen? All of a sudden we have 600,000 people using this drug.”

He also pointed out that other drugs, costing less than $10 a dose, were equally effective.

The Natrecor infusion-for-profit scheme was indeed on a roll. J&J had recruited doctors and nurses with experience in administering infusions to deliver presentations at medical seminars, and some clinics had programs set up to administer Natrecor to patients twice a week for up to 12 weeks. In 2004, Natrecor brought in about $400 million for J&J, and sales were projected to be $700 million for 2005.

However, the profiteers were hit with a ton of bricks on April 20, 2005, when a study appeared in the Journal of the American Medical Association that reported patients treated with Natrecor were 80% more likely to die in the 30 days following the treatment than patients given a placebo, by Dr Jonathan Sackner-Bernstein of the North Shore University Hospital in Manhasset, NY; Drs Marcin Kowalski and Marshal Fox, of St Luke’s-Roosevelt Hospital Center in NY; and Dr Keith Aaronson of the University of Michigan.

On April 26, 2005, in response to the findings of the study, Mr Arbesfeld told HeartWire, “We take any question about the safety of Natrecor seriously.”

“At the same time,” he said, “a review of Scios’s full clinical study data set does not show a statistically significant difference in mortality.”

Although the collective data from the studies reflects a 23% higher death rate for those taking Natrecor, Mr Arbesfeld said, the number of patients in the studies was too small to produce conclusive results of death risk, in a Reuters article on April 25, 2007.

In response to comments about Natrecor not being approved for outpatient use, Mr Arbesfeld told the Times that the FDA label did not specify where the drug could be administered, so giving it in an outpatient setting did not run counter to its approved use.

However, that Mafia guy from the Cleveland Clinic, Dr Nissen, told the Times that treating patients in ambulatory settings was “inappropriate and cannot be recommended.”

Before long, more doctors began speaking out. Cardiologist Dr Milton Packer, chairman of the advisory panel that voted to approve the drug, told the Times on May 17, 2005, that Natrecor was not intended for outpatient use. “We said this is a drug that should be approved for patients who are short of breath at rest, who are hospitalized,” he said.

He also faulted the FDA’s approval of a label that did not specify that Natrecor was for hospital use only.

Dr Sackner-Bernstein expressed outrage in the Health Day Report. “The people involved at Scios and others who knew about this data should be hanging their heads,” he said.

“What is wrong with everybody,” he continued, “that you’ve got a drug that increases renal dysfunction and death, and costs 50 times as much as a regular treatment, and yet it’s given to hundreds of thousands of people?”

After the April study came out, J&J hired a heart specialist, Dr Eugene Braunwald, to form a committee to review the studies, and the committee reached the same conclusion, that it was inappropriate to use Natrecor except with acutely ill hospitalized patients.

Specifically, the panel said, Natrecor should be used only when patients show up at a hospital with acute heart failure; that it should not replace diuretics as the front-line treatment; and that it should not be used where patients schedule appointments to receive the drug ahead of time.

Their report also stated: “Scios should immediately undertake a proactive educational program to inform physicians regarding the conditions and circumstances in which [Natrecor] should and should not be used.”

So what did J&J do in response? According to Dr Packer, who was a member of the panel, the committee members were shocked several weeks later when they received invitations from a mass mailing to enroll in a continuing medical education program, sponsored by Scios, that appeared to promote the outpatient use.

“We were flabbergasted,” Dr Packer told the Times on August 1, 2005. “Scios was sponsoring meetings to discuss nesiritide and its potential use in outpatients.”

As so often happens these days, this drugging-for-profit scheme caught the attention of lawmakers because about 80% of the patients receiving Natrecor were on Medicare.
D-Day came on December 5, 2005, when the Centers for Medicare and Medicaid Services announced that Medicare would no longer pay for outpatient infusions.

But the Natrecor story is far from over because, according to Johnson & Johnson’s 2006 Annual Report, the company received a subpoena from the US Attorney’s Office, District of Massachusetts, in July 2005, seeking documents related to the sales and marketing of Natrecor, and in August 2005, J&J was advised that the investigation would be handled by the US Attorney’s Office for the Northern District of California in San Francisco.

The latest news came on March 12, 2007, when J&J revealed that it had received 3 new subpoenas from the US Attorneys’ offices in Philadelphia, Boston and San Francisco wanting information for the investigation into the company’s sales and marketing of Natrecor.

More recently, in an apparent repeat of the exact same scam, investigators have found that J&J and Amgen have been paying doctors to administer the anemia drugs Aranesp, Epogen and Procrit off label for profit. On May 9, 2007, the New York Times reported that drug makers are paying “hundreds of millions of dollars to doctors every year in return for giving their patients anemia medicines.”

The Times cited documents obtained from a former employee of a group of 6 cancer doctors which showed that between them, the 6 doctors received $2.7 million from Amgen for prescribing $9 million worth of anemia drugs in 2006.

On May 10, 2007, the Wall Street Journal cited a document provided by a former J&J sales representative-turned-whistleblower which showed that a doctor who purchased nearly $1 million worth of Procrit over 15 months would receive $237,885.

In March 2007, the FDA ordered black box warnings on the drug’s labels about an increased risk of numerous adverse events and issued a public health advisory warning health care providers to administer the lowest possible dose necessary to treat anemia.

According to the FDA, as of March 2007, there are five clinical trials that demonstrated decreased survival time in cancer patients receiving the drugs compared with those receiving transfusion support.

The agency also reported a higher rate of blood clots, strokes, heart failure, heart attacks and death were found in patients with chronic kidney failure when the drugs were given to raise hemoglobin levels higher than recommended.

The FDA advisory also noted a higher risk of blood clots in patients who were scheduled for major surgery and received the anemia drugs and also warned of an increased rate of tumor growth in patients with advanced head and neck cancer receiving radiation therapy and metastatic breast cancer patients receiving chemotherapy, when the drugs were given to maintain levels higher than recommended.

J&J is already facing several class-action lawsuits filed by shareholders as a result of the revelation of this latest drugging-for-profit scheme, and the company has also received a subpoena from New York’s attorney general requesting information on the sales and promotional activities related to Procrit.

But then, why should J&J worry over a minor little investigation by the NY attorney general. The feds have been investigating the Natrecor fiasco for more than 2 years, and the J&J executives who reaped the benefits have probably not lost one wink of sleep.