Who Should Serve on Advisory Panels?

A Senate subcommittee next week will consider a bill that will prohibit scientists who work part-time for the drug industry from serving on Food and Drug Administration advisory committees. This legislation is important for rebuilding the public's faith in the deliberations of the agency since when it comes to approving new drugs or pulling unsafe ones from the market, the FDA usually follows the votes of its outside advisers.

Yet the FDA is opposing the bill. One issue raised by opponents is the availability of outside experts without conflicts of interest. They claim there are many medical subspecialties where virtually every physician who has an in-depth knowledge of the disease has at one time or another worked for the handful of companies developing potential therapeutics.

Such would appear to be the case with acute decompensated heart failure, a fancy term for people whose heart-pumping ability has deteriorated to the point where they can't breath or walk. In 2001, Johnson & Johnson's Scios unit developed nesiritide (Natrecor), which is given in large doses intravenously when these dying patients showed up on hospitals' doorsteps. This new, pricey drug replaced massive doses of traditional blood vessel dilators or diuretics.

But this past February, an analysis of all the randomly-controlled trials of Natrecor (mostly done for the FDA) showed that more people died on Natrecor, which severely disrupts kidney function, than on the older therapies. As the article in the Journal of the American Medical Association politely put it, "despite being better than placebo, . . . nesiritide has not clearly been shown to be noninferior to diuretic and conventional vasodilator regimens."

For J&J, what was especially damaging about this news was how it immediately began impacting its business. It wasn't because the hospitals began switching back to the older drugs. Rather, Natrecor's lucrative off-label use began drying up. Hundreds of doctors had been encouraged to give the drug in out-patient settings to people whose hearts were failing but weren't yet on death's door. As today's New York Times pointed out, this procedure, for which a cheap, generic oral diuretic would have worked just as well, cost Medicare $600 per infusion -- not including the cost of the office visit.

So what did J&J do in response to the JAMA article? They asked Dr. Eugene Braunwald, one of the leading cardiologists at Harvard Medical School, to convene an outside advisory panel to review the evidence. Since this wasn't an official FDA advisory panel, there were no open meetings where the public could present evidence. There were no conflict of interest rules governing who could sit on the 9-member panel. Everyone was paid by J&J.

In a phone conversation with Dr. Braunwald today, he informed me that every person on the panel, including himself, had at one time or another had some relationship with the maker of Natrecor (including Scios before it was bought by J&J). Some of those relationships dated back a few years, but conflicts of interest on the panel were universal. "They told me to get the best people to get the best opinion. And to get the best opinion, you need people who have had some involvement," he said. "The final report was pretty tough on them."

Indeed it was. Braunwald and his eight colleagues warned against using the drug in an outpatient setting; asked J&J to immediately begin a clinical trial testing whether this FDA approved drug increases mortality or worsens kidney function; and suggested the company immediately begin a massive outreach campaign to doctors to educate them about problems with the drug.

Did one have to be an expert in this particular form of heart disease to arrive at these conclusions, as Dr. Braunwald and the FDA have suggested? It turns out the lead author of the original JAMA study also had financial ties to the European marketer of Natrecor. It seems that anyone who took a close look at this drug -- other than the FDA -- came to the same conclusion.

Indeed, anyone with the ability to evaluate statistics and who spent a few days reading the studies on this form of severe deterioration in heart function would have come to the same conclusion.

And that's the point: the FDA, or J&J in this instance, could have asked an unconflicted panel of physicians to evaluate the drug. Instead, they sought out physicians who were already on or recently had been on the company's payroll.

This time it worked out for consumers. But imagine what the public would have thought if Dr. Braunwald's panel had said there were no problems with Natrecor. That's why smart companies and the FDA should opt for advisory panels that are untainted by conflicts of interest. It's the only evidence the public can really trust.

Posted by gooznews at June 15, 2005 03:32 PM