How We Do Harm (28 page)

Today, Nexium is one of the most commonly used drugs in the United States.
The joke is on us.
Today, the cost of one dose of prescription Nexium is $6, and over-the-counter Prilosec is about $1.
An equivalent generic omeprazol has been available for $.45 a dose since 2006.

I told one of my patients that she should use the generic of Prilosec, that it’s as effective as Nexium, but cheaper.
She corrected me, explaining that Nexium was new, so it must be better.
Besides, her insurance pays for Nexium and it only cost her a $10 copay.
I tried to explain that a month of generic omeprazole cost $13 over the counter.
Later in the same conversation, she complained that her health insurance cost $18,000 per year.

She seemed to not connect the two.

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SOME
of us with a skeptical streak envision corporate chieftains who don’t want clinical studies performed.
After all, every study carries the risk of demonstrating that your drug is inferior to something else.
Worse yet, a study can show that your stuff is worse than nothing at all.
Indeed, if you don’t look for harm, you don’t find harm.

Had Merck refrained from asking too many questions about its drug Vioxx, it would still be on the market.
Vioxx (generic name, rofecoxib) was a nonsteroidal anti-inflammatory compound, an inhibitor of the enzyme known as cyclooxygenase-2.
There are two cyclooxygenase enzymes.
COX-1 inhibition causes platelets to dysfunction and can lead to increased bleeding.
COX-2 inhibition relieves pain by preventing prostaglandin production.

COX-2 inhibitors can treat pain from inflammation while not increasing bleeding risk.
This is highly desirable, given that most NSAIDs have some COX-1 inhibition, which also has increased risk of gastritis and ulcers.

The giant drug company Merck developed a drug that they called Vioxx as a potential COX-2 inhibitor for the treatment of pain.
To get Vioxx FDA-approved for marketing, Merck conducted a series of trials, which might today be considered comparative-effectiveness research.
The studies compared the approved arthritis-pain drug naproxen to Vioxx and showed the drugs to be equivalent in both pain control and gastric side effects.
The FDA approved Vioxx for relief of pain from rheumatoid arthritis and osteoarthritis, migraine and cluster headaches, as well as menstrual cramps.

In the studies that led to Vioxx’s being approved for sale, the group treated with Vioxx had a fourfold higher risk for cardiovascular events than those on naproxen, 0.4 percent versus 0.1 percent.
The difference might seem small, but it was statistically significant, meaning that it was probably not a fluke.
Why would those taking Vioxx have more heart attacks and strokes?
A number of experts, myself included, thought naproxen was preventing cardiovascular disease through its effect on platelets.
It was known that aspirin, another nonsteroidal anti-inflammatory, prevented heart disease by decreasing the ability of platelets to form blood clots in arteries of the heart.

Vioxx became a blockbuster.
Its 2003 sales were $2.5 billion.
It cost $2.50 per pill or $90 per month.
While it was on the market, more than 80 million people were prescribed this drug worldwide.
Keep in mind that it was FDA-approved because science showed that it was equivalent to $15 a month of naproxen.
The only scientifically documented advantage of Vioxx was that it could be administered to most patients once a day, whereas naproxen is generally administered twice a day.
It was never even shown that Vioxx was safer in terms of stomach bleeding.

Even though sales of Vioxx were superb, the company was trying to figure out how to squeeze even more sales out of the drug.
There was a theory that COX-2 inhibitors would inhibit colon polyp formation.
Some polyps are precursors of colon cancer.
If Vioxx prevents colon polyps, it might mean it would prevent colon cancer.
Another study was conducted.
This study randomized adults to Vioxx or placebo.
It would have been unethical to test Vioxx versus a placebo in the pain-control studies that got it approved, because drugs such as naproxen can treat pain.
But as there is no definite drug to prevent colon polyps, a randomized, placebo-controlled trial in which half the patients would get Vioxx and half would get a placebo was ethically acceptable.

The trial went smoothly until the data safety monitoring committee, a group of experts who get to see the unblended data, noticed a dangerous trend.
The Vioxx arm was associated with a four times higher rate of cardiovascular disease and stroke.

An old friend, Bill Anderson, a great doc and a superb epidemiologist, was one of the investigators on the polyp-prevention study.
While I was not involved in the public debate about Vioxx, he knew that I was certain that the explanation for the increased number of cardiovascular and stroke events in the Vioxx-versus-naproxen studies was that naproxen was preventing them and not that Vioxx was causing them.
He called me one morning and gently told me to start figuring out how the cornstarch in the placebo was preventing heart attacks and strokes.

Of course, it can’t.
Not in a million years.
We clinical researchers call this sort of thing humor.
Naturally, Vioxx was to blame for the excess of deaths on the experimentl arm.

Merck ended up withdrawing Vioxx from the market.
The lawsuits brought by people claiming harm from Vioxx have so far cost Merck more than $5 billion.
We do not know how many people were harmed by Vioxx.
Most of them will never employ a lawyer.

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A
new drug must be better than the old.
A new medical device must also be better.

We spend a lot of money on radiologic imaging.
The CT, computed tomography; MRI, the magnetic resonance imaging: PET, positron-emission tomography—we love that stuff.

But overuse of radiologic imaging is a major problem in the United States.
Up to one-third of radiologic imaging tests are unnecessary.
This is a serious problem, not just because these tests are expensive, but because they expose the patient to radiation that can cause cancer.
Some have estimated that 1 percent of cancers in the United States are caused by radiation from medical imaging.

Looking at the number of scanners per million population, we have three times as many CT scanners in the United States as in Canada.
I am constantly reminding my colleagues not to order a $2,000 CT scan when a $60 chest X-ray will provide the same information.
Better yet, a doctor can use a stethoscope to listen to breath sounds in the chest, which is cheap.

Magnetic resonance imagers are even more expensive than CT scanners.
They don’t give off radiation and are therefore safer than a CT.
MRIs use a large magnetic field to provide an image.
My favorite MRI story is about a hospital that actually started advertising that they had the only 3-Tesla MRI in the area.

What the hell is a 3-Tesla MRI?
For the vast majority of patients needing an imaging study, a 2-Tesla MRI is just as good as a 3-Tesla MRI.
Seeking competitive advantage, the hospital had engaged in nonsensical advertising.

In 2008, when adjusted for population size, the United States had five times as many MRI scanners as Canada.
In researching this book, I called a physician friend at Princess Margaret Hospital in Toronto to see what the wait time for a CT and an MRI scan was.
Then I called the radiology departments at Emory University Hospital and Piedmont Hospital in Atlanta.
The wait was the shortest for both tests at Princess Margaret.

While we may not be able to give Americans the life expectancy that Canadians have (Canada is No.
12 worldwide, with the life expectancy at birth projected at 81.38 years.
The United States is No.
50, with the life expectancy of 78.37 years), our excessive number of CT and MRI scanners sure as hell means that we can take more pictures of people dying.

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THE
da Vinci robot is another expensive device that shows up in commercials and marketing material for numerous hospitals.
This machine can be used for heart-valve replacement, hysterectomy, radical prostatectomy, and other surgeries.
The incisions are smaller than with a conventional surgery, and theoretically, blood loss, pain, and recovery time should be shorter with a robotic operation.
For many operations, more precise cutting is possible without the normal shakiness of the human surgeon’s hand.

I got to play with a da Vinci recently.
A private hospital had an open house to present information on prostate-cancer screening.
They had a demo da Vinci there for patients and curious doctors to play with.
It’s a cool toy indeed.
The doctor has his back to the patient and looks through binoculars to see a three-dimensional image captured by a camera placed through an incision into the patient.
The doctor uses controls, like in a video game, to move three rods that extend from the robot connected to surgical instruments.
I mastered the art of looking through the scope and lifting pennies with the robot.
I realized that anyone who claims to be a robotic surgeon who doesn’t look as if he has spent the last ten years playing video games should get extra questioning.
You don’t want a surgeon with gray hair for this one.

Da Vinci machines cost up to $3 million.
The maintenance contract is $500,000 per year.
The average cost of disposables is about $1,500 per surgery.
Hospitals make up these costs by advertising (another expense) to attract patients looking for new, high-tech, easier treatment.

Free prostate-cancer screening, for example, is a common way of attracting insured patients and paying the mortgage on one of these expensive machines.
I mentioned that the advantages of robotic surgery exist—in theory.

This is an important point, as almost all studies comparing robotic to conventional surgery haven’t demonstrated significant advantages.
Occasionally, a study will show that patients take a few less pain pills.
Some defenders of the technology say that the problem is that most surgeons are still learning to use the robots, and the advantages will be seen after surgeons advance on the learning curve.
I say maybe.
Or maybe not.

Da Vinci is better for some surgeries, compared to an open procedure, but this new technology is being overused and its results are often exaggerated.
I worry that we are training a generation of surgeons who may be so dependent on the robot that they will lack the confidence to perform an open procedure when that open procedure is needed.

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ANOTHER
overused, expensive therapy is intensity-modulated radiation therapy (IMRT).
This high-tech treatment is provided by a linear accelerator the size of an SUV—approximately ten feet high and fifteen feet long.
The machine alone can cost up to $3 million.
The size of the machine usually entails building and construction costs for installation.

IMRT creates a pencil-thin beam of radiation.
It allows for fine targeting of the area to be treated.
This, in theory, means that less good, healthy tissue near the cancer is damaged as the tumor is radiated.

These machines are being used most extensively to treat cancers of the prostate, head and neck, and the central nervous system.
IMRT has also been used to treat breast, thyroid, lung, gastrointestinal, and gynecologic malignancies and certain types of sarcomas.
Some patients and some diseases should be treated with IMRT, but most patients with cancer do not need it.
Conventional orthovoltage radiation is just as good.

In 1998, IMRT was available at 4 percent of radiation oncology facilities in the United States.
By 2003, 38 percent of radiation therapy centers had this technology, and it is available at the majority of centers today.
It can cost $60,000 to $80,000 to treat a tumor with IMRT, when the same cancer can be treated with conventional orthovoltage radiation for $10,000 to $12,000.

Some studies show that IMRT is better in treating certain tumors, but it’s being used more and more in cancers where studies don’t show a benefit to the patient.

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PROTON
beam therapy is the newest radiation-therapy technology.
A machine shoots charged particles called protons, placing radiation into a tumor with no radiation exiting the tumor.
The radiation literally stops in the tumor.
This creates much less collateral damage to surrounding normal tissues.

This is useful for the treatment of tumors in confined areas with sensitive tissues nearby.
For example, brain tumors near the pituitary and hypothalamus are best treated with proton beam therapy.
However, proton beam therapy is being used more and more in treatment of diseases in which there is no clear evidence of an advantage.
Some are actively trying to prevent studies from being done.
Reimbursement for unnecessary proton beam therapy is even better than reimbursement for unnecessary IMRT.

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LEGISLATION
in 1989 proposed the creation of the Agency for Healthcare Research and Policy.
The acronym was unfortunate: AHCRAP.
The name was quickly changed to the Agency for Healthcare Policy and Research.
(In 1999, the name was changed to the Agency for Healthcare Research and Quality, AHRQ.)

Politicians almost always support basic research, but rarely support studies on the effectiveness of treatment.
Yet the leap from interesting science to clinical application is huge, yet difficult and important to pinpoint.
AHCPR began with unusually strong bipartisan support.
A number of studies demonstrated tremendous variations in medical practice throughout the country and significant inappropriate use of services.

To combat these problems, AHCPR sponsored grants to form Patient Outcomes Research Teams (PORTs), multidisciplinary centers based primarily at university medical schools and schools of public health.
The teams were to focus on specific medical problems—appendicitis or heart attacks, for example—and review and synthesize available research, analyze practice variations and patient outcomes using administrative data augmented by primary data collection, disseminate the results, and evaluate the effects of dissemination.