Reversal of Fortune

All over the medical blogs this week, there’s been discussion of Merck’s withdrawal of rofecoxib (Vioxx) and the gathering storm of tort lawyers and class action suits (look at the ads to the right of this google search for some indication of what's coming).

Of course, many are gleeful that a greedy corporation will get what's coming to them. Others worry about the stifling effect on new drug research.

If this stifling effect is true, it should be quantifiable. The data can come in several forms: Measurable delays in drug approvals, or the abandonment of research projects following litigation involving similar drugs.

In other words: Are there instances where the development of a useful drug was delayed due to frivolous litigation, either by diverting company resources or forcing additional, unnecessary trials? Can we find answers to questions like "How many patients died of disease X, while the FDA held up approval on drug Y for unnecessary review?"

Because after we get some answers, some numbers, then we can go after someone to hold liable. (I realize this is the opposite of how it normally works -- these lawyers begin with a target, and then look for victims). It just seems like the regulators and trial lawyers are never held accountable, at least not to the standard that the pharmaceuticals firms are. The assumption with these lawsuits is always: 1) the drug company knew their product was unsafe and 2) rushed to sell it anyway.

This can be a persuasive argument for a jury, and has the benefit of being true sometimes. But a compelling argument can similarly be made if you change your assumptions, and gather some data.

If it can be shown that, with a little hindsight, livesaving drugs were 1) on the way to market and 2) delayed by regulatation or litigation, well, suddenly the burden is on the regulators and lawyers to explain why people were suffering. And suddenly, they're vulnerable to suits, too.

It seems far-fetched, sure, but ought to be easier to prove than McDonald's liability for America's obesity.

Of course, suing McDonald's wouldn't make Americans thinner. But targeting overzealous tort lawyers and stringent but ineffective regulators might make patients healthier.

I don't have many potential examples, because my school don't often teach us the history of the drugs we have to memorize (too bad, it might make it easier). But here's one story I've heard: Researchers knew since the early 70's that the antipsychotic drug clozapine (Clozaril) had fewer anticholinergic side effects (like odd, uncontrollable movements) than the mainstay therapy, haloperidol (Haldol). But Clozaril wasn't approved, because early trials on a small population showed an unacceptably high level of another side effect (agranulocytosis -- fewer white blood cells). The drug development was abandoned.

When reviewers repeated the trial years later, in a larger population, they found the incidence of this agranulocytosis was much lower than previously thought. The drug finally came to market in 1989. But how many Haldol patients developed debilitating movement disorders in the meantime? Could early lawsuits against antipsychotics have had a stifling effect on developing clozapine? And who can we sue to get these people some justice?

Another possibility is drotrecogin alfa (Xigris), a new drug to help patients with overwhelming infections (severe sepsis). Though Xigris is a recombinant form of a naturally occurring human protein (protein C, involved in clotting), the FDA held up its approval of Xigris pending the usual safety trials.... plus they demanded economic studies, as well.

Even now, Xigris is only approved for really sick septic patients. That's not because the drug doesn't work on healthier patients -- it does -- but treating these healthier patients is not deemed cost-effective. Of course, these septic patients could still crash and die, but too bad. Our courts have told doctors that using evidence-based cost-effective measures is malpractice, if the outcome is ever unfavorable. So critical care doctors may be vulnerable, though I'm not aware of any suits brought against FDA.

And when it comes to issues of liability, it seems like agencies charged with public safety ought to share in the blame. The FAA has been sued over airline accidents, for instance. So when a drug gets FDA approval and makes it to market, only to be voluntarily withdrawn years later when the company finds it's risky in some circumstances (as is the case with Vioxx), why not target the FDA? Some reports already indicate it was understaffed and lenient.

Of course, going after regulatory agencies, or individual trial lawyers, won't produce the financial windfall of suing pharmaceuticals. But like they say: this isn't about the money, it's about justice. Right?