Crawford's pledge

Acting Food and Drug Administration commissioner Lester Crawford made several pledges Thursday during his confirmation hearing. Since the hearing received only minor news coverage (thanks to the over-hyped baseball steroid hearings), it’s worth highlighting one his promises because we’ll get a chance in the next few weeks to see how seriously he takes reform.

According to the Wall Street Journal, Crawford pledged to revamp the agency’s process for disclosing conflicts of interest among members of its advisory committees. A spokesperson later amplified his comment. The FDA is "reviewing ways to make our current process for providing disclosures more transparent and readily available to the public,” she said.

Sen. Ted Kennedy (D-Mass) raised the issue after a dozen public interest groups sent a letter to Crawford demanding changes in the advisory committee process. At the mid-February hearing on the safety of COX-2 painkillers, at least ten committee members had direct ties to either Pfizer, Merck or Novartis, which make drugs in that class. Had their votes been excluded, at least two of the three Cox-2 drugs on the market would have received a thumbs-down vote.

The promise of greater and more timely disclosure by itself doesn't meet the demands of the public interest groups. Their letter demanded that all future advisory committees exclude outsiders with direct ties to manufacturers whose products are being discussed at the meeting (the FDA almost always follows the advice of its outside advisory committees). The letter also demanded that the number of scientists on a committee with any ties to industry never exceed half.

The groups then went on to seek process reforms, asking for greater disclosure and a 30-day comment period on any panel's make-up. At present, the FDA usually announces its panels the day before the meeting and often leaves the public in the dark on advisers’ corporate ties. It was these latter process reforms that Crawford presumably was addressing in his response to Kennedy.

April will provide the public with ample opportunity to judge how seriously the FDA takes this issue. Its Cardiology and Renal Drugs Advisory committee meets April 5th to discuss expanding the labeling for Norvasc, Pfizer’s calcium channel blocker for hypertension that is already the third largest selling drug in America. Pfizer, the world’s largest drug company, spreads tons of research dollars around and employs dozens of leading cardiologists as part-time consultants and speakers. Indeed, the chairman of the standing committee is Dr. Steven Nissen of the Cleveland Clinic, who just published a Pfizer-funded study praising Norvasc.

The FDA will have to reach beyond the usual suspects if it doesn't want more bad publicity about conflicts of interest on its advisory panels. It can be done. There are thousands of cardiologists in this country, including hundreds who teach at the nation’s 125 medical schools. Surely the agency can find advisers who know the science, have the skills to interpret clinical trial data and aren’t on Pfizer’s payroll. It will be interesting to see if they try.

A second opportunity comes the following week when the FDA’s General and Plastic Surgery Devices advisory committee meets to evaluate the safety of silicon gel breast implants. This touchy field is filled with conflicting science claims and protracted litigation, which makes it all the more important that scientists and surgeons with ties to the manufacturers keep their hands off.

FDA on the Hot Seat

I missed posting a GoozNews last week because, to be frank, I was too busy. Between an explosion of activity at the Center for Science in the Public Interest (more on that below), a paid writing gig and two Maasai singer/dancer/warriors staying at our home during their U.S. tour, something had to give.

But the world didn’t stand still. Immediately after the President’s Day holiday, the New York Times called the CSPI Integrity in Science project, which I run, to see if there were conflicts of interest among the 32 panelists who voted to keep the three Cox-2 drugs on the market. Within 24 hours, the two researchers at the project, Simone Baribeau and Christine Ishiwata, turned up at least 10 scientists with direct financial ties to Merck or Pfizer, the manufacturers of the drugs, or to Novartis, which has a Cox-2 in its pipeline.

The resulting front page article last Friday triggered an avalanche of outrage and not just from the usual quarters. Sen. Charles Grassley (R-Iowa), chairman of the Senate Finance Committee, fired off a series of probing questions to the FDA asking why it allowed scientists with conflicts of interest on the panel, which was a direct violation of the Federal Advisory Committee Act. Take their votes away and two of the three drugs would have been voted down.

The FDA’s leadership has a gun pointed at its feet and stuck on automatic. In the wake of the antidepressant and painkiller fiascoes, legislation to create an independent safety arm within the agency is gathering momentum. The understaffed safety department is currently housed within the drug approval wing, thus creating a structural conflict of interest. Will people who approve a drug later listen to underlings who say they made a mistake?

Meanwhile, FDA deputy Sandra Kweder testified on Capitol Hill this week that the agency needs more power to order label changes on drugs when the agency thinks stiffer warnings are warranted. Currently they negotiate with the companies, often leading to long delays before warnings get disseminated. It was a curious statement. Why doesn’t the agency simply say, “Negotiation over. Change the label.” Memo to Kweder: You already have the power. What’s missing is the will to challenge a powerful industry with lots of friends in the White House and on Capitol Hill.

Finally, look for the FDA to come under increasing pressure in the coming weeks to revamp its advisory committee process. The New York Times this morning editorialized that "unless the FDA makes a more aggressive effort to find unbiased experts or medical researchers start severing their ties with the industry, a whiff of bias may taint the verdicts of many advisory panels."

The agency in charge of determining if our food is safe and our drugs are safe and effective needs to “just say no” when it comes to putting industry consultants with direct conflicts of interest on its advisory panels, whose advice the agency invariably follows when approving new products.

It’s a big country. I’m sure they can find qualified scientists who are not on company payrolls. If they stick to the line that they can’t, then perhaps we’ve discovered the reason for high drug prices – every doctor in the country is on the take. The fact is that too many of them are. But many are not, and it’s time the FDA rewards their independence by giving them the coveted slots on its influential advisory panels.

Bioterror Brain Drain Revisited

Two days ago more than 750 scientists, including two Nobel Prize winners, signed a petition to NIH protesting the priorities of the nation’s war on bioterrorism. They decried the fact that grants for research on anthrax and five other potential bioterror agents have increased fifteenfold since 2001 despite the fact that almost no one gets sick from these diseases. Meanwhile, grants to study feared pathogens like drug resistant tuberculosis and malaria, which kill millions around the globe every year, have decreased 27 percent from their already inadequate levels.

I wrote about this issue in October 2003 in The American Prospect (see “Bioterror Brain Drain”). So I immediately emailed Richard Ebright, a Rutgers University microbiologist who helped organize the petition, to congratulate him. He wrote back saying he had read my article and agreed with it.

Throughout the 20th century, scientists played a key role in building opposition to the misuse of science and technology. One need only recall that many leading physicists turned against the Cold War nuclear arms race. It’s good to see this tradition reasserting itself in the 21st century in fields like global warming and infectious disease research.

NIH – The Backlash Builds

The Wall Street Journal today gave major play to the backlash building at the National Institutes of Health against its strict new conflict of interest rules, which ban all outside financial ties to drug, biotechnology and medical device firms. This follows up on an earlier Washington Post report that said many of the NIH scientists’ failures to report financial ties with business, which had been uncovered by a Congressional subpoena, actually had been reported.

The articles prominently quoted members of a new group of senior NIHers who are calling themselves the Assembly of Scientists. Their claim: the rules “seriously overreach and will severely and irreparably compromise the NIH’s mission.”

As discussed in the Feb. 6 GoozNews (see “Protecting the View from Mt. NIH"), I think those arguments are hogwash. So I was glad to see once again David Willman of the Los Angeles Times, who broke the original story about double dipping at NIH, digging up more dirt that other papers either failed to find or didn’t want to report. Willman reported at least a third of the members of the Assembly of Scientists have received stock, stock options or other financial payments from drug and biotechnology companies, including one scientist who’d received 500,000 shares.

Cox-2s and the Future of Medicare

Here’s the label you won’t read on Celebrex, Bextra and Vioxx (if Merck decide to bring Vioxx back):

WARNING: This drug increases your risk of a heart attack or stroke. This drug provides no more pain relief than generic and over-the-counter painkillers. There is no reason to take this expensive, prescription drug unless you are among the 1 to 4 percent of people who suffer from gastrointestinal side effects from other painkillers, which are available at one-tenth the price at your local supermarket or drug store without a prescription. Nearly half of all heart attacks are fatal and those who survive must deal with the consequences for the rest of their lives. Only one in 20 ulcers are fatal and the vast majority of gastrointestinal problems are easily treated with few long-term effects.

There are two differences between that label and a typical FDA warning label. It compares the risks and benefits. And it talks about the relative economic value of the drugs.

The FDA advisory panel that met for three days last week to discuss the fate of COX-2 inhibitors never discussed the economic value of this class of drugs. As a top FDA official once described the agency’s mandate to me: the FDA doesn’t consider the relative usefulness of a new medicine within the range of potential medical approaches to a problem. It only considers whether a new drug is safe and effective.

That’s no longer an adequate mission. What a new drug, medical device or procedure is actually worth will be the most important question facing medical consumers and the health care system over the coming decades. It’s a question that is already front and center for taxpayer-financed Medicare, whose prescription drug benefit goes into effect next year.

Estimates for the ten-year cost of that program are now pushing $700 billion. In a letter to President Bush this week, Sen. Ted Kennedy (D-MA) and Rep. Henry Waxman (D-CA) urged the administration to negotiate lower drug prices, something prohibited in the Republican-backed Medicare prescription drug bill that passed in late 2003. Such negotiations, they said, could save taxpayers $190 billion. Bush appointee Mark McClellan, the former FDA commissioner and now head of the Center for Medicare and Medicaid Services (CMS), immediately rejected that approach. He claimed the insurance companies administering the benefit will wrest concessions in a competitive market.

That’s nonsense. The insurance companies, despite the huge administrative costs they add to the health care system, have proved totally inept at evaluating the relative worth of medical services as a way of holding down health care costs. Their meat axe approach on physician and hospital services wound up denying needed care to millions of Americans. The backlash against managed care became a potent political issue. Properly chastened, the insurers put down their axes and became pass-through agents for health care costs still rising at near double-digit rates. They still collect their fees, of course.

The core problem with most managed care and an unfettered drug marketplace is that they fail to deliver medical value commensurate with the increasing level of money spent. COX-2 sales reached a stunning $7 billion a year for pain relief that could have been had for a tenth the price. Even if one generously assumes that ten percent of those patients qualified for the drugs because of high gastrointestinal risk, the health care system could have saved $5 billion or more a year by making wise decisions.

Of course, the only way to ensure the health care system makes such value-oriented decisions is by establishing drug formularies with clear and enforceable usage guidelines. Unfortunately, the Medicare law restricted the use of formularies. The authors of most usage guidelines are on industry payrolls as researchers, consultants and speakers. Meanwhile, physicians in their offices are bombarded by drug industry salesmen wielding ginned up studies that impart almost no useful information and by patients clamoring for the latest, heavily advertised drugs.

Liberals who want to protect and expand the nation’s social insurance systems need to begin talking about the incredible waste in the health care system that pads the top and bottom lines of drug and device companies and other providers. Paul Krugman, in an otherwise excellent essay in the current New York Review of Books about the Bush administration’s Social Security scam, acknowledges that the real fiscal crisis caused by an aging society is in its health care programs. However, he buys into the argument that technological innovation may be driving health care costs higher. Pointing to the case of implanted cardiac devices, he says that since it saves lives, “it’s not clear that a rising share of health care spending in the economy should be considered a bad thing.”

Technological innovation is one cause of higher health care costs, but like most economists, he only sees the forest and the not the trees. As I discussed in the January 20th GoozNews (“Shocking”), the ICDs are a classic case of bracket creep in medical technology: What’s extremely valuable in some cases often gets deployed through lobbying, marketing and specious research in populations where the technology is less and less useful and in many cases totally inappropriate.

We need a regulatory system that can sort out those questions with sound and objective evidence. We need a health care delivery and payments system that can put that advice into practice. Otherwise, Medicare like Social Security will become prey to bogus privatization schemes masquerading as individual choice since “we can’t afford everything.” That will destroy the program, not save it.