In another significant win for medical journal editors in their new role as regulators, Bayer suspended sales of anti-clotting drug Trasylol (aprotinin), which had been implicated in kidney failure, cardiovascular problems and mortality risk. The drug had approximately $135 million in 2007 sales.
We have no special knowledge of Trasylol. All we can say is that for anyone watching the industry (assuming someone is watching the industry), the Trasylol saga will be another sad chapter.
Officially, the company said it had made the decision on its own. But the word about Trasylol’s safety issues had been widely covered by news organizations, which speculated on the drug’s recall. In an official statement late in October, the FDA noted that new evidence had pointed to a greater risk of death with Trasylol than comparable drugs. So this week’s decision was a surprise only in its timing.
Trasylol was first marketed in 1993. But researchers in Canada had recently halted 6-year BART trial, which had expected to enroll 3,000 patients. Preliminary data reviewed by a data safety monitoring board (DSMB) for the study had clearly been alarming to the DSMB and FDA. The registry listing for the BART trial has not been updated; it suggests the trial is still under way. That listing is here.
One of the lines in another FDA statement on the drug, issued late in October, was pretty bleak: “The DSMB concluded that continued enrollment of patients into the aprotinin group was unlikely to significantly change the study findings.”
But were doctors scanning the headlines to guide their use of the drug? Hardly. Here’s a recent quote from US News: “This is not really new news. It has been surfacing in the past year and a half,” said Dr. W. Douglas Weaver, president-elect of the American College of Cardiology and co-director of the Heart & Vascular Institute at Henry Ford Hospital in Detroit. “Many surgeons have stopped using the drug.”
The FDA’s statements and Bayer’s statements were both out of sync with actual medical practice. Why? They came late. We don’t want to shock anyone, but many doctors still read ... medical journals. The Journal of The American Medical Association (JAMA) and the New England Journal of Medicine (NEJM) had sounded the alarm about Bayer’s drug in early 2006. Bayer, for its part, insists only a handful of suits have been filed and that the suspension of the drug is temporary.
It’s appropriate for the FDA to wait for more data before making a decision. It’s appropriate for journals to publish data. It’s important for industry to let ongoing studies proceed until a clear safety signal flashes.
The more difficult question is: who’s in charge? Congress? FDA? EMEA? Journal editors? It’s not clear. Perhaps it’s the occupant of the White House. This week President George Bush declared that if he had his way, “the FDA would be empowered to order a recall when a company refuses to recall their product voluntarily, or moves too slowly in removing the unsafe product from the market.”
Given limited federal budgets and vast problems in Chinese and other imports (toys, foods and drugs), it is unclear whether there will ever be adequate resources to monitor and inspect everything. We doubt it. What’s more, the timing for making any statutory change appears to be years away.
Back in September, as many readers may recall, Congress passed and Mr. Bush signed legislation reauthorizing industry user fees. That legislation took years to negotiate. But it didn’t significantly alter the landscape. It didn’t provide greater clarity for companies or consumers. Basically, what nonlawyers need to know is that everything is at the FDA head’s discretion.
That means that why and when drugs are withdrawn will be a fluid and unpredictable thing. If you have a slow day, you can read the text of the new law, formally known as the Food and Drug Administration Amendments Act (FDAAA) of 2007, which can be read at a lousy Congressional website that doesn’t allow legislation to be bookmarked.
In fairness to Congress, there are some tough timelines in the new law. At various stages of FDA’s review of new data, it or a sponsor may have 15 days, 5 days, and other very quick periods in which to make decisions. (We can’t help wondering if everyone involved has the systems and electronic data necessary to make those decisions.)
We’re also left with an unsettling feeling that there are several drug safety clocks. All are ticking at different rates. The journal editors have a clock. It runs fast. The regulators have their clock. How fast it runs depends on where you sit; it may appear slow or fast. Ditto for industry’s clock. We need one clock. It’s a shame Congress couldn’t give us one.
Depending on whose clock you’re looking at, you can look at the Trasylol situation and be appalled that the drug took years to be withdrawn, as this AP story suggests. You could also be furious that the drug isn’t available when your surgeon needs it.
The industry and the public thus find themselves in a lamentable situation. With well-distributed authority across squabbling stake holders in government, academia, industry and medical societies, we have a mess. A big one.
The levers to pull to keep good drugs (or get bad ones off the market) have never been more ambiguous. There will be more Vioxxes, more Avandias, more Trasylols—and a grim Wall Street waiting game around which drugs are soon to be taken down by which medical journal.d9A2t49mkex