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.