In 2006, the Vermont Supreme Court upheld a jury decision in state court to grant Levine $6.7 million from Wyeth on grounds that the company should have more expressly prohibited IV pushing on the drug's labeling. Wyeth appealed, arguing that, because the packaging was FDA approved, patients had no right to question it through state laws. In effect, Wyeth claims that federal approval preempts state-based challenges to regulatory standards.

The Preemption Wars




This principle of preemption makes for one of the most heated and important Court cases in a very long time. Levine is really about more than just drug labeling: it's about whether or not the FDA can be second-guessed, even after a patient has been harmed by a product that the agency has approved.




Earlier this year, the U.S. Supreme Court upheld this principle in deciding that preemption applied to medical devices in the case of Riegel v. Medtronic. New Yorker Charles Riegel and his wife, Donna, brought suit against Medtronic Inc. after a catheter it had manufactured burst inside Riegel's coronary artery during heart surgery. In February, the High Court ruled against Riegel in an 8-1 decision.




When the Court announced its decision, I lamented Medtronic's victory as a "blank check" for medical device makers in that it effectively shields them from law suits once they manage to get FDA approval for their products. But the stakes around Levine are even higher -- in the words of the Times, Monday's case is the "next frontier" in preemption.




That's because, at its heart, Riegel was a question of statutory interpretation. In 1976, Congress passed a Medical Device Amendment to the Food, Drug, and Cosmetic Act (FDCA), the law that effectively created the FDA. This amendment expressly calls for preemption in the regulation of medical devices. As such, the Court's decision was relatively simple, albeit ultimately dangerous. In that case, the Justices pretty much just read the letter of the law.




But Levine isn't so cut-and-dried. There's nothing in the broader Food, Drug and Cosmetic Act that constitutes an express intent to preemption. There is no preemption clause. Thus, as NYU law professor Catherine Sharkey put it to the Times, Levine "challenges the court to define the parameters of preemption outside the safe confines of the legislators' text."




In other words, Monday's decision will decide if preemption is valid even when legislation doesn't explicitly call for it -- if, in effect, the way we regulate drugs in the United States of America prevents injured patients from bringing suits against drug companies that have FDA approval for their products.

Taking Sides




This case will make law. If the Court rules in favor of Wyeth, patients effectively lose their right to sue a drug company, even if its product harms them in an unexpected way. An FDA stamp of approval would essentially function as a shield from law suits. 




To the pro-business crowd, this sounds just peachy. In June, the Bush Administration, a long-time proponent of preemption, filed an amicus brief with the Court on behalf of Wyeth. The administration argued that the FDA's "thorough evaluation" of new drugs should not be questioned. The Bushies specifically note that, in approving a drug, the FDA strikes a particular balance between risks and benefits.  "[S]tate laws that strike a different balance" necessarily "conflict with the FDA's determination," they say, and in such a conflict the federal government's assessment should come out on top. Hence there's an "implied preemption" to all of the FDA's decisions.




The Chamber of Commerce also filed a brief urging the Court to rule against Levine, as did PhRMA, the pharmaceutical manufacturers association. PhRMA insists that the state tort laws that allow patients to sue drug companies pose "significant risks to public health and to FDA's ability to accomplish its mission." In PhRMA's view, a win for Levine would force "pharmaceutical companies to inundate the FDA with requests for labeling changes to ensure that federal regulators have been presented with every potential labeling permutation." In turn, this will supposedly "distract agency scientists from their core mission of reviewing the safety and effectiveness of prescription medications."




When the Bush Administration, the largest business lobby in the country and the drug industry are all arguing that we should respect the authority and integrity of federal regulators, you know something's up. And indeed it is: conservative forces know that the FDA is one of the most impotent federal regulatory agencies we have.




Earlier this year, a former legal counsel to the FDA estimated that the agency needed to double its budget and expand its staff by 50 percent in order to effectively regulate the $1.5 trillion worth of goods that falls under its purview. Strapped for resources, in recent years the FDA has instituted a "user fees" program through which drug companies pay extra to speed up approval of their products. Every year the agency hauls in close to $400 million -- or almost 20 percent of its total budget -- from this program. That's right: about one-fifth of the FDA is directly bankrolled by the prescription drug industry.




Most drug companies pay the fees for expedited approval, which means that the under-staffed, under-funded FDA is often scrambling to get approvals out the door. Last year an FDA insider told Health Beat that the mad rush for approval compromises the quality of the agency's oversight. According to the source, drug companies are "betting that, because [the FDA wants] to make the [expedited] deadline [for reviewing and approving new drugs], we won't send the application [for approval] back. If you find a problem or there is something missing [from the application] and it doesn't seem terribly material, there is a tendency to overlook it. Because if you don't it will just delay the whole process." Time pressures mean that FDA regulators "send [a drug submission] back [only] if it's really crappy."




It's no wonder that the drug industry is so eager to give the FDA the final word in drug safety: the agency is gradually becoming a rubber stamp factory that survives on corporate pharmaceutical money to operate. There's no easier regulatory process to navigate than the one you control. As Dr. Marcia Angell, a former editor of the New England Journal of Medicine (NEJM), recently told the Wall Street Journal: "the FDA has been given over to the industry it regulates."

An Inexact Science




Even if the FDA were operating efficiently and effectively, it would still be unreasonable to insist that its decisions preclude any future legal challenges to drug safety. In a commentary published earlier this month in support of Levine, the Journal of the American Medical Association (JAMA) noted that "the drug and device regulation process is at best an inexact and incomplete science."




Indeed, no matter how honest FDA regulators may be, "the current approach of basing drug approval decisions on clinical trials of efficacy that include relatively small numbers of patients virtually guarantees that the full risks and complete safety profile of these drugs will not be identified at the time of approval." You can't really know what will happen when millions of people take a drug for years if you've only tested it on dozens of people over a few months. The FDA is a regulatory body, but it's not omniscient.




Moreover, because the Agency has been pushed to approve drugs as quickly as possible, many are "fast-tracked" through the agency. This means that they are rushed to market before there is time to know how patients who take it will fare over the long-term. In theory, manufacturers are supposed to continue long-term trials, and report the results to the Agency. But in practice many ignore this regulation, and the FDA doesn't have the funding to enforce post-market surveillance. So much for what the Bush administration calls the FDA's "thorough evaluation" of new drugs.




Drug companies are betting on the FDA's limited knowledge -- and are eager to limit it further. As the NEJM noted in a brief filed in support of Levine -- the first such document to have the full support of the publication's full roster of past and present editors -- "pharmaceutical companies...[often] learn about dangers caused by their drugs long before the FDA does...[and do not] disclose this information to the FDA."




Consider the case of Trasylol, a clotting drug used during heart surgery to prevent bleeding that was linked to increased probability of kidney damage and death. Bayer pharmaceuticals, the drug's manufacturer, knew that it was associated with severe kidney damage since the 1980s, but the company ignored this evidence and a steady stream of similar studies over the next decade. In 1993, the drug was brought to market and wasn't pulled from the shelves until November of last year, after the Canadian government had to stop large clinical trials of the drug because too many patients in the study group were dying.  Researchers estimate that 22,000 lives could have been saved had the drug been recalled sooner.




There's also Vioxx, Merck's blockbuster $2.5 billion painkiller. In 2001, company scientists discovered that patients who took their drug were at a threefold risk of death due to heart problems relative to placebo patients. They withheld this information from the FDA for two years before law suits began popping up around the nation and the drug was pulled from shelves in 2004.




Other examples: internal documents show that drug maker Eli Lilly consciously played down the risks of Zyprexa, a drug for schizophrenia that causes major weight gain in many patients, for years. In the late 1990s, court investigators found that Wyeth had known that its weight-loss drug cocktail of Pondimin and Redux was causing a rare heart valve disease on a much wider scale than had been reported to federal regulators.




These are just a few examples of how the drug industry conceal risks. As the Medicare Payment Advisory Commission noted in its June 2008 report to Congress, "researchers have shown that bias in industry-sponsored trials is common."




The problem is that the manufacturers control the trials of their own products. Big Pharma is virtually the only industry that is not subject to third-party evaluation of the safety of its products. Imagine if we let automakers oversee crash tests on new models, allowing the industry report results, as it sees fits, to the government and consumers. This would  never happen: we have the U.S. the National Highway Traffic Safety Administration (funded by taxpayers) and  the Insurance Institute for Highway Safety (funded by insurers) to run safety trials.




But in the case of drugs that have the power to kill or maim patients, drug makers themselves monitor the trials. Thus, when it comes to protecting patients, law suits and court orders have played a unique role in bringing the true dealings of drug companies into the light. Often, transparency and accountability must be forced on these companies through legal proceedings. As the JAMA commentary puts it, "tort law serves in effect as a way to close regulatory gaps in the FDA premarketing approval process and to provide a mechanism for postmarketing surveillance." But if the Supreme Court decides in favor of Wyeth, we're less likely to ever see internal documents that show what drug companies know and don't know at any given moment, because we'd see fewer court orders and fewer law suits.




It's hard to pinpoint how many personal injury law suits would be thrown out should the Court decide that FDA approval preempts any other claims that drugs are unsafe. The L.A. Times puts the number in the "tens of thousands" and JAMA says that such a "decision would likely result in thousands of lawyers defending drug manufacturers to file motions in state courts to dismiss plaintiffs' claims under preemption." Thousands of people like Diana Levine would lose their only recourse for redress.




This, of course, would be great news for Big Pharma, which spends billions on law suits every year. In 2005, Eli Lilly spent $700 million to settle 8,000 lawsuits over Zyprexa, Between 1998 and 2006, Wyeth spent $15 billion to resolve lawsuits over Pondimin/Redux. In November, Merck offered a $4.85 billion settlement to cover some 27,000 lawsuits over Vioxx, but only after spending $1.2 billion in order to get to the settlement stage. Some analysts expect the Vioxx debacle will ultimately cost the drug giant somewhere around $30 billion. This year Bayer announced that it faced 78 law suits in the U.S. over Trasylol. 




Do we really need all of these law suits to keep the prescription drug industry in check? Surely, even if the Supreme Court were to uphold preemption, medical research into prescription drugs would continue, and we'd find out what's safe and what isn't, right?




Wrong. As we've seen, if you leave truth-seeking only to company researchers, the drug companies will do all they can to ignore or suppress unpleasant results. And without the threat of legal action to serve as a deterrent to misconduct, poor clinical trials becomes little more than bad press. Drug companies are well-equipped to deal with the press: they spend about $57 billion a year on marketing -- almost twice what they spend on R & D.

The Blank Check




When the Supreme Court decides Wyeth v. Levine on Monday, it will effectively be deciding whether or not prescription drug companies get a blank check from the government. A victory for preemption will mean that, so long as a company can manipulate the FDA -- or cover-up the risks of its product -- it will never be held accountable for the harm its products and decisions cause patients around the country. An industry forecasted to hit $842 billion in sales in 2010 would be told that its only public safety hurdle is the FDA -- an toothless agency that operates on industry dollars.




Diana Levine's case is about much more than the wording of a drug label. It's about transparency and accountability, about industry's hold on the federal government, and about patients' right to protect themselves. Let's hope the Supreme Court makes the right decision.