Monday, October 30, 2006

Conflicts of Interest at the Transcatheter Cardiovascular Therapeutics Conference

Business Week last week reported the latest complicated tale about interactions between physicians, research, and commercial firms. The story centered on Dr Martin B Leon, Associate Director, Center for Interventional Vascular Therapy, Columbia University Medical Center, who also is the chairman of the Cardiovascular Research Foundation, which runs the Transcatheter Cardiovascular Therapeutics (TCT) conference. Leon was co-founder of the CTC in 1988. Businessweek summarized his relationships with some device manufacturers.

Leon's first consulting arrangement with a company grew out of the inaugural TCT in Washington. Marvin Woodall, who headed Johnson & Johnson's new cardiac-devices division, asked Leon to serve as the unit's paid ex-officio medical director.

Through the 1990s, Leon and other interventional cardiologists had links with companies they didn't routinely acknowledge at the conference.

Leon and TCT have provided a launching pad for many small companies. 'It is the premier forum for the introduction of new technology,' says Howard Leonhardt, CEO of Bioheart Inc., which is developing several cardiac devices. Leon agreed to serve on the company's scientific advisory board in 2000. 'He introduces us to the right people,' Leonhardt says. 'He's a prominent leader at the cutting edge.'

In 1999 he co-founded a company called Percutaneous Valve Technologies Ltd. (PVT), which developed a cardiac valve that could be implanted by a catheter snaked through an artery, rather than open-heart surgery. When Edwards [Lifesciences], based in Irvine, Calif., bought PVT for $125 million in early 2004, Leon collected his roughly $6 million. In addition, he and other PVT shareholders were promised a total of three $10 million payments upon the achievement of three milestones: the successful treatment of 50 patients, regulatory approval in Europe, and limited approval in the U.S.

To comply with Columbia's policies, Leon has recently simplified his web of financial relationships. Earlier this year, he says, he donated his rights to the Edwards milestone payments to a school in Manhattan, which he declines to identify. That is so he can participate in current clinical trials for the PVT valve, which has been refined since the 2004 live case. And in 2005 he gave up the $257,679 annual salary he had been drawing from his foundation. But he makes no apologies for accepting payments from manufacturers. 'If you expend a significant amount of time and effort' helping a company develop a new device, he says, 'there will be financial remuneration.'

Another complicated Leon relationship concerns Abiomed, a company in Danvers, Mass. In 2005, Leon's incubator, Accelerated Technologies Inc., sold a small company called Impella to Abiomed for $42.2 million in stock. Impella had invented a tiny pump that helps the heart do its job and can be implanted in minutes. Three versions of it are on sale in Europe, and the company is conducting clinical trials in the U.S. Leon received stock then worth nearly $1 million, plus the opportunity to receive a small share of up to $16.75 million in milestone payments, based in part on Abiomed's regulatory approvals and units sold.

Businessweek raised questions about how the products of companies with which Leon had financial relationships were presented at TCT, the conference he runs.

n September, 2004, with thousands of doctors at the conference watching live by satellite on giant screens, a cardiologist in Milan inserted an experimental heart valve into a gravely ill patient. Suddenly the patient's heart began to fail. For 45 minutes the stunned audience watched a series of desperate life-saving attempts, until finally the satellite transmission was cut. The patient died later that day. 'It was harrowing,' says Dr. Martin B. Leon, the New York heart specialist who started the influential conference 18 years ago. 'That was a very difficult thing for us.'

Leon's anguish over the incident remains palpable, but he also had a financial interest in seeing the valve work. He co-founded the small company that invented the device. That company was sold to Edwards Lifesciences....

At TCT ... in 2004, Leon disclosed the relationship simply as 'PVT-Edwards,' one entry in a list of 26 companies from which he received equity, consulting fees, or research grants. He didn't spell out the potential milestone payments in the TCT materials. Doctors who watched the live procedure that ended with the death of the patient in Milan might not have known that the conference's leading figure had an intricate and continuing relationship with the manufacturer of the device being implanted.

Did Leon's financial stake in the experimental device play a role in its being promoted at an important conference where he is the most prominent figure? 'Absolutely not,' Leon says. The question, he adds, 'borders on being offensive.'

[However,] 'Things that Marty is part of get exaggerated attention' at the conference, gripes the CEO of one device startup. The CEO declined to be identified out of fear he would offend Leon and imperil his company's treatment at TCT.

Mostly undisclosed until six years ago, the tangle of physicians' financial interests at TCT is now acknowledged in a booklet distributed to participants. In 2005 no fewer than 345, or 44%, of the more than 750 doctors and researchers who made presentations at TCT had received compensation from companies, some of whose products they evaluated at the conference.

Beyond the danger that conflicts may distort individual clinical decisions, some TCT observers worry that the event engenders a general excess of enthusiasm for complicated device-based procedures.
TCT undeniably stirs excitement about devices. When new products perform well in the live cases--real-time procedures beamed in from hospitals all over the world and viewed at the conference--a crowd of animated doctors and investors typically gathers around the booths of the relevant manufacturers. 'Marty turned the medical meeting into the auto show,' says Dr. Stuart F. Seides, associate director for cardiology at the Washington Hospital Center.

At TCT, Leon makes speeches, presents data, and comments on some live cases. He is "a mixture of teacher and showman," says Dr. Patrick W. Serruys, chief of interventional cardiology at the Thoraxcenter-Erasmus University in Rotterdam....

[After Leon received Abiomed stock and the opportunity to receive milestone payments,] Six months later, [the Abiomed device] Impella was featured in two live cases at TCT. At the same conference, Abiomed co-sponsored an evening event featuring doctors talking about heart pumps. Leon, who was the keynote speaker, noted briefly in the disclosure booklet and on a slide that preceded the presentation that he was a "major shareholder" of Impella-Abiomed.

This latest case raises the same sort of questions about conflicts of interest raised by other recent cases (for example, see this recent post). But first I ought to deal with the objections raised by Dr Leon above to the notion that his financial relationships may have affected what he said or how he ran to the conference. As we have noted before, people may not realize at a conscious level how conflicts of interest affect their thinking. But, " people who have conflicts of interest often find giving clear advice (or opinions) particularly difficult" (see post here). Furthermore, if a physician receiving a pen or coffe mug with a company logo may create a conflict now considered unacceptable at some academic institutions (see posts here and here), then why would a researcher or academic having relationships worth tens or hundreds of thousands of dollars be acceptable?

So, is Dr Leon's work at the Cardiovascular Research Foundation and the TCT only educational and scientific, or does he also act as a marketer for the many companies he also works for? Should the sorts of presentations at TCT described above be taken as just scientific and educational, or also as marketing? Does the Cardiovascular Research Foundation only do research and education, or does it also do marketing? Does marketing in the guise of impartial education and research peformed by disinterested physicians and researchers lead to an "excess of enthusiasm?" Finally, are the physicians, educators, and researchers at TCT misusing the trust placed in them by the physicians and scientists attending the conference, and the public at large, by working for commercial device manufacturers as well as academic institutions?

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