- The Washington Times - Monday, June 18, 2001

Congressional staffers are investigating claims of mismanagement and influence peddling involving the committees that evaluate the safety and efficacy of new drugs.
Investigators of the House Government Reform Committee say they are examining all 32 of the Food and Drug Administration advisory committees, which are composed of specialists from academia, research facilities and industry. However, they are focusing now on the Cardiovascular and Renal Drugs Committee.
That group is especially important. Heart disease remains the nations top killer, so the search for cures continues to be a high priority and drug makers willingly spend many millions on research and development in hopes of cashing in on a huge prescription drug market.
The investigators are:
* Analyzing documents that show certain physicians with multiple ties to heart-drug manufacturers have been retained on the committee for extended periods in defiance of FDA regulations.
* Looking into assertions that certain committee members are using the knowledge and influence gained from long FDA tenure and the implied promise of favorable consideration to gain consulting positions from drug makers or employment as designers or directors of late-stage clinical trials.
The yearly retainer for consulting and fees for conducting a clinical trial ranges as high as $200,000. One drug company executive who asked not to be identified referred to the advisory committee members approaches for obtaining such work as "shakedowns" because a company that refused to yield to requests could doom products that cost tens of millions of dollars to develop.
One in five Americans — roughly 61 million — have some form of cardiovascular disease and 4.7 million have been diagnosed with congestive heart failure, the American Heart Association reports. Heart disease currently kills nearly a million people a year. So the number of people potentially affected by the issue is large.
The concern is that those critically needing more effective heart medications may be poorly served because certain FDA advisers may, for personal gain, push approval of inferior products while opposing superior ones.
The implications for the highly competitive drug companies also are immense because of the huge sums spent on developing and testing medicines to meet the governments tough drug-approval criteria. Drug makers say they want the process to be fair.
Since at least 1972, the FDA has relied on independent specialists in science and medicine working as part-time "special government employees" to study and evaluate drugs submitted for approval. Beginning in 1976, advisers were hired to judge medical devices, too.
At the request of FDA officials, the committee members analyze detailed test results and the voluminous documentation submitted by medical products makers. They then meet periodically at public hearings to listen to and quiz the manufacturers who come to explain and pitch their wares. The advisers are paid nothing for their document analyses, but they earn $386.80 a day for participation at hearings and are reimbursed for travel at coach-class rates.
"Most of the advisers earn more than $386 a day at their regular jobs. They do this work for the FDA as a public service," said John Treacy, director of the FDAs advisers and consultants staff.
Aside from that, "Being selected for a committee confers prestige, and the members learn the workings of the FDA," Mr. Treacy said.
Dr. Craig Pratt, Baylor University professor of medicine and former chairman of the Cardio-Renal Committee, said: "To be picked is an acknowledgment of expertise. I considered it an honor. Sitting on the committee is a tremendous education. Think of it — on that one day of the hearing you get to hear all of the research on a drug — the pros and cons. Thats something you cant do any other way. Its exciting.
"The idea that the committee is made up of a special in-crowd is as far from the truth as possible," he added.
However, the idea may not be far-fetched.
As Mr. Treacy explained, the FDAs rules limit committee membership to four years. Members cannot be reappointed to a committee again until at least a year has elapsed. They cannot serve on a committee longer than eight years in any 12-year period.
But consider the record of the current Cardio-Renal Committee chairman, Dr. Milton Packer.
Dr. Packer is a renowned heart failure specialist. He is chief of circulatory physiology and director of the Center for Heart Failure Research at New Yorks Columbia-Presbyterian Medical Center. He has been serving on FDA committees almost continuously since 1986.
FDA documents obtained by The Washington Times show Dr. Packer was appointed a member of the committee in 1986 with his term to end in 1990. Yet a 1992 document mentioning the doctors appointment to serve as an "expert" with the Cardio-Renal Committee notes he is "already on board as a committee member."
Other memos and pay documents show the doctor has served the committee either as member, "consultant" or "expert" every year through 1996.
In 1997, he was appointed to a four-year term as committee chairman.
Dr. Packer confirmed he was first appointed to the committee in 1986. He said he served his term, then left the committee for years before his reappointment as chairman.
He added that he has "no knowledge that would support the concerns of the Government Reform Committee."
Many of the documents establishing a committee members affiliation with the Cardio-Renal Committee are requests for "waivers," and that demands explaining:
Before every advisory committee hearing, committee members are required to fill out disclosure forms and voluntarily declare whether they have a "conflict of interest" — especially a financial conflict — regarding any of the drugs or medical devices that will be discussed in the course of the coming meeting. The FDA defines a financial conflict of interest as the "potential for gain or loss as a result of government action on a particular matter."
Commonly, the members do have some connection with the product or product maker. They may own stock in the manufacturers company. They may have served as a paid consultant to the drug maker or have been paid to design or test the drug makers product.
The advisers also may have had indirect association with the product because colleagues in their laboratories worked on the products or because the clinic or institution for which they work has some research or financial arrangement with the product or the manufacturer.
FDA officials peruse the members voluntary disclosures. But because the process is based on the "honor system," they do not check for accuracy or completeness.
Ultimately, agency officials can approve the member for full voting participation in a given hearing, allow the member to participate but not vote, or disqualify a member from a particular hearing.
Often though, FDA officials find the declared conflicts to be inconsequential or to involve less than, say, $10,000, which is deemed too little to generate bias. Just as frequently, the FDA acknowledges a member has a serious conflict of interest, then argues that because the member has special knowledge or expertise, the conflict will be "waived." The member then may proceed as if the conflict did not exist.
Consequently, an adviser who has helped develop a drug can help decide whether it is safe and effective.
The system has come under fire lately.
Last summer, Rep. Dan Burton, the Indiana Republican who heads the Government Reform Committee, wrote Donna Shalala, then secretary of health and human services, charging that "conflict-of- interest rules employed by the FDA … have been weak and inconsistent, enforcement has been lax and committee members with substantial ties to … manufacturers are routinely given waivers to participate in committee proceedings."
Mr. Burton wrote that certain committees were "dominated by individuals with close working relationships" to drug makers.
"This was never the intent of the Federal Advisory Committee Act, which requires that a diversity of views be represented on advisory committees," he stated.
The congressmans conclusions were based on his staffs "extensive review of financial disclosure forms and related documents, … minutes of committee meetings" and interviews.
USA Today also reviewed documents and did a computer analysis of FDA hearing records last year. It revealed that "54 percent of the time, [advisers] have a direct financial interest in the drug they are asked to evaluate."
The newspaper found that "at 92 percent of the meetings at least one member had a financial conflict of interest," and "at 55 percent of meetings, half or more of the FDA advisers had conflicts of interest."
The FDAs Mr. Treacy and others pointed out, however, that the scientists and physicians who have most to offer as advisers are the ones manufacturers most want to hire as researchers and consultants.
Thats surely true of Dr. Packer.
Records show he has or has had direct ties to 17 major manufacturers of cardiovascular drugs during his tenure as an FDA advisory committee member, consultant or expert.
He routinely receives conflict-of-interest waivers, for the FDA values his judgment.
In a memo urging Dr. Packers appointment as committee chairman, Dr. Raymond Lipicky, the director of the FDAs Cardio-Renal Drug Products Division, wrote that Dr. Packer has been an "outstanding" member of the committee.
"He was unfailingly able to identify major issues, to detect major deficiencies (and to convince others who had not detected them that the deficiencies existed). … [Dr. Packers] breadth of experience is absolutely unique. …"
Moreover, a pharmaceutical company executive, who knows Dr. Packer but asked not to be named, said Dr. Packer is "very, very intelligent. A pleasing person, charming and engaging and the best presenter of data among cardiologists — a unique guy."
That said, its easy to see why drug companies would benefit from employing someone like Dr. Packer, whose professional virtues include extensive knowledge of FDA workings and drug-approval requirements.
On the flip side, its easy to see why advisers who will sit in judgment of a drug makers product might have little difficulty convincing manufacturers that its wise to use their services as a consultant or clinical trial director — and foolish not to.
Such work from drug makers provides advisers fodder for producing scientific papers — the stuff with which great academic reputations and medical fame are built.
Then, too, as still another drug company executive put it: "Every little $175,000 fee helps."
Because the motive and opportunity for influence-peddling exist, the Government Reform Committee has taken seriously reports that it is occurring. Yet it is tricky to establish.
Drug company executives have nothing to gain and something to lose by reporting an advisers pressure tactics. The same can be said of advisers colleagues and underlings.
As Mr. Treacy, the director of advisory committees, put it in a different context: "An important aspect of the advisers is their independence. They cannot be removed except for special cause. Which has never happened."

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