A federal drug official on Friday dealt a severe blow to the popular diabetes drug Avandia, issuing a scathing review of a major clinical trial that its manufacturer has been using to argue that the drug was safe.
The reviewer, Dr. Thomas Marciniak of the Food and Drug Administration, found a dozen instances in which patients taking Avandia appeared to suffer serious heart problems that were not counted in the study’s tally of adverse events.
Such repeated mistakes “should not be found even as single occurrences” and “suggest serious flaws with trial conduct,” Dr. Marciniak wrote.
The detailed report could prove crucial next week, when a panel of experts will meet to consider whether to recommend to the F.D.A. that the manufacturer, GlaxoSmithKline, withdraw Avandia from the market or restrict its sale.
The panel’s decision will have broad consequences for the company, the F.D.A. and perhaps even the entire process by which medical products are approved. The agency almost never does clinical trials on its own, depending on drug companies to conduct them appropriately.
Avandia, which helps patients get better control of blood sugar levels, has already come under intense criticism. It has been shown to increase the risks of bone fractures and to cause swelling that can lead to heart failure and eye problems.
And a number of studies, including some by GlaxoSmithKline, suggest that it could increase the risks of heart attacks, strokes and death. But the company has relied heavily on the major clinical trial, nicknamed Record, to demonstrate that those risks are exaggerated.
Dr. Marciniak’s review of the Record study calls that assertion into question. He found one case in which a seizure patient was hospitalized for bleeding in the brain, but all mention of the episode was deleted from records. Another patient was hospitalized for 67 days after a severe stroke, but the study record showed no sign of a cardiovascular problem.
Still another died after being hospitalized for a serious heart problem, but the death was listed as arising from an unknown cause and not heart-related.
Correctly interpreted, he concluded, the study actually supports critics’ contentions that Avandia may cause heart attacks and strokes. “One does not have to be a mathematician or to perform calculations,” he wrote, to come to the conclusion that a combined look at all the trials of Avandia would demonstrate that it causes heart attacks.
Mary Anne Rhyne, a spokeswoman for GlaxoSmithKline, said the study demonstrated that Avandia is safe and added, “The Record study was conducted according to good clinical practices and the data are reliable.”
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Reading this blog you may get the impression that I can't make up my
mind if I am serious or silly. Yet I think we all need a portion of both
in our lives. I do my best to keep the balance and hope you enjoy the
experience.
The more you look at the problems involved in overhauling our health-care system, the more hopeless they seem. But that is exactly what made Peter Neupert, a Microsoft millionaire and dotcom entrepreneur, want to try. “It is completely overwhelming,” he says. “My wife reminds me all the time that there are many things a lot simpler that I could be doing. But I just have a genetic predisposition for big, hairy problems.”
That’s why, in 2005, having already made two fortunes—as a Microsoft executive and then as CEO of Drugstore .com—Neupert returned to Microsoft to create software for health-care providers. His division, the Health Solutions Group, now has 800 employees and sells to hospitals nationwide.
Neupert’s basic premise, oversimplified, is that one key to improving health care involves installing modern software that can make the system more efficient and ultimately enable patients to get better service at a lower cost. The need for this kind of change is obvious to anyone who, like myself, is hitting the age when we need to see doctors more often and/or is the parent of young kids. Keeping track of our health information is a complicated kludge just begging to be digitized. Why is it so easy for me to manage a 7,000 song music collection, yet so hard for me to keep track of my kids’ vaccinations? We now do almost everything online: banking, travel planning, shopping. But when we go to the doctor we still do things pretty much the way we did them a half century ago. Too much still gets done on paper. Even when your medical information is stored digitally, the data often can’t be shared among providers.
If you show up in an emergency room with a bad cut, they’ll want to know when you had your last tetanus shot. But you probably have no idea—and no idea how to find out. That’s a simple example. Imagine you’re a diabetic, seeing several doctors, nutritionists, and therapists. Each one keeps records, but they don’t share them. “At its core, health care really is an information-management business,” Neupert says.
The church will be closed tomorrow, and the drunks are freaking out. An elderly lady in a prim white blouse has just delivered the bad news, with deep apologies: A major blizzard is scheduled to wallop Manhattan tonight, and up to a foot of snow will cover the ground by dawn. The church, located on the Upper West Side, can't ask its staff to risk a dangerous commute. Unfortunately, that means it must cancel the Alcoholics Anonymous meeting held daily in the basement.
A worried murmur ripples through the room. "Wha… what are we supposed to do?" asks a woman in her mid-twenties with smudged black eyeliner. She's in rough shape, having emerged from a multiday alcohol-and-cocaine bender that morning. "The snow, it's going to close everything," she says, her cigarette-addled voice tinged with panic. "Everything!" She's on the verge of tears.
A mustachioed man in skintight jeans stands and reads off the number for a hotline that provides up-to-the-minute meeting schedules. He assures his fellow alcoholics that some groups will still convene tomorrow despite the weather. Anyone who needs an AA fix will be able to get one, though it may require an icy trek across the city.
That won't be a problem for a thickset man in a baggy beige sweat suit. "Doesn't matter how much snow we get—a foot, 10 feet piled up in front of the door," he says. "I will leave my apartment tomorrow and go find a meeting."
He clasps his hands together and draws them to his heart: "You understand me? I need this." Daily meetings, the man says, are all that prevent him from winding up dead in the gutter, shoes gone because he sold them for booze or crack. And he hasn't had a drink in more than a decade.
The resolve is striking, though not entirely surprising. AA has been inspiring this sort of ardent devotionfor 75 years. It was in June 1935, amid the gloom of the Great Depression, that a failed stockbroker and reformed lush named Bill Wilson founded the organization after meeting God in a hospital room. He codified his method in the 12 steps, the rules at the heart of AA. Entirely lacking in medical training, Wilson created the steps by cribbing ideas from religion and philosophy, then massaging them into apithy list with a structure inspired by the Bible.
The 200-word instruction set has since become the cornerstone of addiction treatment in this country, where an estimated 23 million people grapple with severe alcohol or drug abuse—more than twice the number of Americans afflicted with cancer. Some 1.2 million people belong to one of AA's 55,000 meeting groups in the US, while countless others embark on the steps at one of the nation's 11,000 professional treatment centers. Anyone who seeks help in curbing a drug or alcohol problem is bound to encounter Wilson's system on the road to recovery.
It's all quite an achievement for a onetime broken-down drunk. And Wilson's success is even more impressive when you consider that AA and its steps have become ubiquitous despite the fact that no one is quite sure how—or, for that matter, how well—they work. The organization is notoriously difficult to study, thanks to its insistence on anonymity and its fluid membership. And AA's method, which requires "surrender" to a vaguely defined "higher power," involves the kind of spiritual revelations that neuroscientists have only begun to explore.
What we do know, however, is that despite all we've learned over the past few decades about psychology, neurology, and human behavior, contemporary medicine has yet to devise anything that works markedly better. "In my 20 years of treating addicts, I've never seen anything else that comes close to the 12 steps," says Drew Pinsky, the addiction-medicine specialist who hosts VH1's Celebrity Rehab. "In my world, if someone says they don't want to do the 12 steps, I know they aren't going to get better."
