The Origins of the Cholesterol Con, Part II

Last week, I wrote about the “cholesterol con,” the widespread belief that “bad Cholesterol” ( LDL cholesterol) is a major factor driving heart disease, and that cholesterol-lowering drugs like Lipitor and Crestor can protect us against fatal heart attacks. These drugs, which are called “statins,” are the most widely-prescribed pills in the history of human medicine. In 2007 world-wide sales totaled $33 billion. They are particularly popular in the U.S., where 18 million Americans take them.

We thought we knew how they worked. But last month, when Merck/Schering Plough finally released the dismal results of a clinical trial of Zetia, a cholesterol-lowering drug prescribed to about 1 million people, the medical world was stunned. Dr. Steven E. Nissen, chairman of cardiology at the Cleveland Clinic called the findings “shocking.”  It turns out that while Zetia does lower cholesterol levels, the study failed to show any measurable medical benefit.

This announcement caused both doctors and the mainstream media to take a second look at the received wisdom that “bad cholesterol” plays a major role in causing cardiac disease. A Business Week cover story asked the forbidden question, “Do Cholesterol Drugs Do Any Good?" 

The answer, says Dr. Jon Abramson, a clinical instructor at Harvard Medical School, and the author of  Overdosed America, is that “statins show a clear benefit for one group—people under 65 who have already had a heart attack or who have diabetes. But,” says Abramson,  “there are no studies to show that these drugs will protect  older patients  over 65—or younger patients who are not already suffering from diabetes or established heart disease –from  having a fatal heart attack. Nevertheless, 8 or 9 million patients who fall into this category continue to take the drugs, which means that they are exposed to the risks that come with taking statins –which can include severe muscle pain, memory loss, and sexual dysfunction.”

Finally—and here is the stunner—it turns out we don’t have any clear evidence that statins help the first group by lowering cholesterol levels.  It’s true that they do lower cholesterol, but many researchers are no longer convinced that this is what helps patients avoid a second heart attack. It now seems likely that they work by reducing inflammation. In other words, these very expensive drugs seem to do the same thing that aspirin does.  (Are they more effective than the humble aspirin? We’ll need head-to-head studies to find out.)

Update on FDA Stories: Business as Usual

In my last two posts, I touched on some pretty significant FDA-related developments—and even though they’re barely a week old, a lot has happened since my commentary. Here’s a look at where things stand now. It’s not pretty.

The FDA, Avastin, and Wall Street

In a post last week, I urged the FDA not to approve Avastin for use with breast cancer patients, because (1) the science shows it’s not effective enough to warrant approval and (2) giving it the okay would set a precedent for approving mediocre drugs..

Naturally, the FDA approved Avastin at the end of last week.

In a comment quoted by MarketWatch, analysts called the FDA’s decision “a welcome outcome” because "investors and companies have expressed growing concern that the FDA's hurdle for approving drugs is a moving target and that a survival benefit is a necessity.”

But wait—just last week the Wall Street Journal noted that FDA “evaluation methods have remained largely unchanged over the last half-century.” In fact, the Journal cited this long-term consistency as emblematic of the agency’s “bureaucratic culture”—and yet here are the analysts, claiming that the problem is inconsistency.

Of course, the logic behind approval is a secondary concern to investors—what really matters is the financial consequences of an FDA decision. In this case the green light from the FDA sent Genentech shares shooting up by almost 10 percent in a single day. Predictably, financial analysts see big things in the company’s future: the investment bank Cowen & Co. forecasets  a peak potential sales estimate of $1.5 billion in 2012 and RBC Capital Markets analysts have upped their 2008 and 2009 sales forecasts by $17 million and $30 million respectively (the drug’s 2007 sales already clocked in at a whopping $2.7 billion).

As the Army Approaches a Breaking Point

Since 9/11, one Army division has spent more time in Iraq than any other group of soldiers: the 10th Mountain Division, based at Fort Drum, New York.

Over the past 6 years and and six months, their 2nd Brigade Combat Team (BCT) has been the most deployed brigade in the army. As of this month, the brigade had completed its fourth tour of Iraq. All in all, the soldiers of BCT have spent 40 months in Iraq.

At what cost?  According to a February 13 report issued by the Veterans for America Wounded Warrior Outreach Program, it is not just their bodies that have been maimed and, in some cases, destroyed. Many of these soldiers are suffering from severe mental health problems that have led to suicide attempts as well as spousal abuse and  alcoholism.

Meanwhile, the soldiers of the 2nd BCT have been given too little time off in between deployments:
In one case they had only six months to mentally “re-set”  following an eight-month tour in Afghanistan–-before beginning a 12- month tour in Iraq.

Then, in April 2007, Secretary of Defense Robert Gates decided to extend Army tours in Iraq from 12 to 15 months—shortly after the BCT had passed what it assumed was its halfway mark in Iraq.

As the VFA report points out:  “Mental health experts have explained that ‘shifting the goalposts’ on a soldier’s deployment period greatly contributes to an increase in mental health problems.”

The Supreme Court’s Medical Device Decision Misses the Point

Last week the Supreme Court ruled that medical device-makers are protected from personal injury lawsuits so long as their products have passed the most stringent FDA approval process. The principle that the Justices cited in their decision was “preemption”—the idea that the FDA stamp of approval is final, binding, and supersedes any problems or malfunctions that may subsequently occur.  This means, more or less, that if your pacemaker blows up the device-maker can shrug and say “sorry buddy, the FDA gave it the okay; you’re on your own.”

As harsh as this may sound, there is an argument to be made for preemption. The principle was pretty clearly written into a 1976 medical device law and the pro-business contingent has a point when it says that without some degree of preemption, competition is nigh impossible (it’s tough to navigate 50 different state codes, and the companies that can are the big, established ones).

But regardless of the principles behind the Court’s decision, the practical dimensions of the ruling leave much to be desired. Preemption only has teeth if the FDA does—but the agency is all gums.

For years, the FDA has been in a state of steady decline. According to a former FDA chief counsel, the agency's staff has shrunk 14 percent over the last 14 years. Experts say the FDA needs a 15 percent boost in funding per year for the next five years in order to be effective, and a November report revealed that the FDA barely has any computers or personnel infrastructure.

In short, the FDA is a mess, and the entropy hasn’t spared medical device regulation. To help fill its empty coffers, since 2002 the FDA has had a system in place that allows device-makers to pay fees in order to expedite product inspections. It is estimated that between 2007 and 2012, the FDA will collect $287 million in fees from medical device companies—just over a fifth of the total cost to the FDA to review new devices.

The Wall Street Journal Is Wrong on Avastin

Today the Wall Street Journal ran an editorial urging the FDA to approve Avastin, a drug used to help treat colorectal cancer, for breast cancer. It’s an angry—and ultimately, wrong-headed—piece.

In December, an FDA advisory committee voted against allowing Avastin for breast cancer treatment; the FDA is expected to make a final decision this weekend that either affirms or rejects the committee’s recommendations. The Journal supports a rejection the committee (and approving the drug) because “in clinical trials, Avastin demonstrated the longest reported ‘progression-free survival’ for patients with advanced breast cancer.” In other words, patients “live longer before their disease spreads or worsens” when they take the drug. So, says the WSJ, the FDA has a moral obligation to approve Avastin, because it “translates into an improvement in quality of life by delaying the onset of symptoms.”

But in reality the situation isn’t nearly this simple—and for all its good intentions, the Wall Street Journal trips over its own logic.

Clinical trials show that Avastin plus paclitaxel (the scientific name for the brand drug Taxol) helped to keep cancer from growing for five months longer than in patients on paclitaxel alone—this much is true. But there’s more: as an American Cancer Society summary of the original December decision notes, “overall survival was not significantly better [for those who took Avastin] and women who received Avastin had more serious side effects compared to those who got paclitaxel alone.”

The Journal is quick to note that “not significantly better” refers to the fact that women on Avastin “lived slightly longer, a median of 26.5 months compared with 24.8 with Taxol alone.” That means that, even though cancer was slowed for five months, the average lifespan of an Avastin-taker was ultimately only lived two-months longer than it was for those who didn’t take the drug. The newspaper is angry that the FDA trivializes this time be deeming it a statistically insignificant extension. But there are other things to consider besides time—like side-effects.

A Lesson in Health Care Innovation...from the Government?

Government gets a bad rap in American politics. Not all of it is undeserved, mind you, but one thing that isn’t deserved is the accusation that the public sector is unable to innovate. In fact, for some of the innovations that matter the most—like electronic medical records—the public sector might just be our best bet for progress.

Consider the example brought up by Jack E. Lohman, a Health Beat reader who comments on Wisconsin politics. Responding to one of my posts, Lohman offered information about VistA, the Veteran Administration’s electronic health records system. Lohman notes that VistA works by “instantaneously search[ing] for patients around the country with similar diseases and lists the physicians’ treatments and successes, grouped by the most common treatments.” In other words, it aggregates and cross-compares data to see which treatments have worked for which kinds of patients.

This information is then matched up with “a one-time, lengthy health questionnaire that would be turned over to the physician for evaluation.” Translation: patients are surveyed to see where they fit in the VistA database so that doctors can better assess their situation. (This might sound familiar: it’s similar to Germany’s system of “diagnosis-related grouping,” which I mentioned in a post last month).

VistA is a great tool—and, I would argue, one that exemplifies the benefits of getting the public sector involved in health care IT.

The Cholesterol Con--Where Were the Doctors? Part I

After the stock market bubble burst, the New York Times asked: “Where were the analysts? Why didn’t they warn us?”

To be perfectly honest, this was a somewhat disingenuous question. As experienced financial journalists understood all too well, the analysts plugging the high-flying issues of the 1990s were employed by Wall Street firms raking in billions as investors bet their nest eggs on one hot stock after another. It really wasn’t in their employers’ interest for analysts to tell us that their products were wildly over-priced.  When a small investor wades into the financial world, there are two words he needs to keep in mind: “caveat emptor.”

But physicians, I firmly believe, are different from the folks employed by Merrill Lynch. (I don’t mean to knock people who work at ML. I am simply saying that they have a very different job description.)  When consulting with your doctor, you should not have to be wary. You are not a customer; you are a patient. And your physician is a professional who has pledged to put your interests ahead of his or her own.

This brings me to the question I ask in my headline: during the many years of the Cholesterol Con—where were the doctors?  When everyone from the makers of Mazola Corn Oil to the Popes of Cardiology assured us that virtually anyone could ward off heart disease by lowering their cholesterol, why didn’t  more of our doctors raise an eyebrow and warn us : “Actually, that’s not what the research shows” ?

No doubt, you’ve heard about the recent Business Week cover story, “Do Cholesterol Drugs Do Any Good?", which blew the lid off the theory that “statins”-- drugs like Lipitor, Crestor, Mevacor, Zocor and Pravachol -- can cut the odds that you will die of a heart attack by slowing the production of cholesterol in your  body and increasing the liver’s ability to remove L.D.L., or “bad cholesterol,” from your blood.   

It’s true that these drugs can help some people—but not nearly as many as we have been told. Moreover, and this is the kicker, we don’t have any clear evidence that they work by lowering cholesterol.

Although medical research suggests that statins can definitely benefit one group—men under 70 who already have had a heart attack--researchers are no longer convinced that the drugs stave off a second attack by lowering the patient’s cholesterol. The drugs do lower cholesterol, but that is not what helps the patient.

Final Update On "Checklist"

In December I wrote about a government effort to block  the use of checklists in ICU's.

Yesterday, I received an e-mail from Robert M. Wachter, MD, Professor and Chief of the Division of Hospital Medicine UCSF Medical Center, headlined: "a happy ending to the checklist story (thanks for your help)

Wachter sent this link to a story on his website which explains that "The Office for Human Research Protections (OHRP) – part of the U.S. Department of Health and Human Services – has concluded that Michigan hospitals can continue implementing a checklist to reduce the rate of catheter-related infections in intensive care unit settings (ICUs) without falling under regulations governing human subjects research."

Wachter commented "I must admit, I didn’t hold out high hopes that a ragtag band of committed clinicians and other quality improvers could change federal policy. But we’ve done just that. If the Feds are capable of rectifying this mistake, who knows what might be next!

Indeed.

Can Insurers Add Value?

Over at American Prospect, Ezra Klein offers a sharp, well-reasoned critique of our for-profit insurance system.

First, he points out that when insurers offer us many choices – catastrophic plans, high-deductible plans, consumer-driven plans with high co-pays –what they are really doing is “turning their attention to making deals with the most profitable among us, and avoiding deals, or finding ways to break contracts, with the least profitable. They are very innovative in their attempts to do this. But there's nothing good about those attempts. Competition among drug dealers does not aid the neighborhood, and currently, competition among insurers does not aid the ill.”

In fact, Ezra stresses: “It is actually counterproductive for insurers to compete on giving us the best care. It's not simply that they're not doing it, but given the structure of the marketplace, they shouldn't do it. Imagine insurer X creates the best damn diabetes protocols in the country. And they begin advertising this fact. What happens on Day Two? Well, they're flooded with individuals suffering from diabetes, or individuals who fear they will one day be suffering from diabetes. These people, in the current system, are a bad deal. Not only is it near impossible to insure them at a profit, but pooling their costs (which is what insurers do, after all) raises premiums for all the insurer's other customers . . .”

This explains why insurers so rarely compete on quality. Most often, they compete on price. And watch out when they do that. This is a market where you get what you pay for, and a less expensive policy is likely to be filled with holes that will open, like trap doors, when you become sick.

Is there any way that we could force private sector insurers to add value to our health care system?

Klein offers Tyler Cowen’s prescription for how, “in a more perfect world,” insurers might compete to offer better service, not just cheaper coverage.  But they would have to be tightly regulated.

Check out Klein’s full post here. It will also link you to Cowen’s argument.

A Blueprint for Healthcare Reform

On this blog, we have often debated these questions: “Why is U.S. healthcare so expensive? Why is it that states like Massachusetts and California just can’t seem to find a way to provide high quality, affordable medical care for all of their citizens?”

In the past, I have suggested that the answer can be found in the work done by Dr. Jack Wennberg and his colleagues at the Dartmouth Medical School. The story that I have posted below provides the narrative behind that assertion, tracing how, over a period of thirty years, Wennberg and his team uncovered the incredible, incontrovertible waste in our health care system.

Wennberg’s work reveals that roughly one out of three of our health care dollars is squandered on unnecessary tests, ineffective, unproven, sometimes unwanted procedures and over-priced bleeding-edge drugs and devices that are no better than the less expensive products that they have replaced.

Only a Luddite would fail to appreciate the wonders of 21st century medical technology. And Wennberg is no Luddite. He is quick to acknowledge that the most expensive, aggressive care that U.S. doctors and hospitals provide is often the most effective care.

But not always. This is what is less obvious. It would seem that by spending so much more than other countries, we would be buying the best care on earth. But the evidence shows that, often, we are not. And therein lies the conflict at the heart of our money-driven health-care system: while more health care equals more profits, it does not necessarily lead to better health.

The story below, which I wrote for the winter issue of Dartmouth Medicine, will, I think, give readers a much clearer understanding of the importance of the Dartmouth research. It begins in the early 1970s, when Wennberg realized that if his home were located just 100 yards farther north, his children would be in a school district where 70 percent of all children received tonsillectomies. Instead, they lived in a school district where there was only a 20 percent chance that they would undergo the operation.