Overdosed America (16 page)

In
September 2001 an unprecedented alarm
was sounded. The editors of 12 of the world’s most influential medical journals, including the
Journal of the American Medical Association,
the
New England Journal of Medicine, The Lancet,
and the
Annals of Internal Medicine,
issued an extraordinary joint statement in their publications. In words that should have shaken the medical profession to its core, the statement told of “draconian” terms being imposed on medical researchers by corporate sponsors. And it warned that the “precious objectivity” of the clinical studies that were being published in their journals was being threatened by the transformation of clinical research into a commercial activity.

The editors said that the use of commercially sponsored clinical trials “primarily for marketing . . . makes a mockery of clinical investigation and is a misuse of a powerful tool.” Medical scientists working on corporate-sponsored research, the editors warned, “may have little or no input into trial design, no access to the raw data, and limited participation in data interpretation.”

Commercial influence on medical research raises two kinds of concerns: First, what is being studied? Those who pay the piper get to call the tune. The drug companies’ funding buys them the right to set the research agenda. The result of commercial sponsorship is that medical knowledge grows in the direction that maximizes corporate profits, in much the same way that plants grow toward sunlight. The questions that do get answered, and thus become our medical knowledge, are often not the ones that will contribute most to improving our health.

Second, is commercially sponsored research “disinterested,” or neutral, enough to stand as good science? There is mounting evidence that it is not. One would have expected that, after the editors’ extraordinary warning of the mounting threat to the integrity of clinical research, scientific business would not just go on as usual; that this public airing of concern about the health of our medical science would have created a stir in the media and alerted doctors across the country to the commercial bias in their most trusted source of medical knowledge. But it didn’t, and most doctors still hold fast to the basic tenet of their training: that the scientific evidence reported in respected peer-reviewed medical journals is to be trusted and serve as the basis of good medical care.

Studies repeatedly document the bias in commercially sponsored research, but the medical journals seem powerless to control the scientific integrity of their own pages. In 2003, separate studies were published in JAMA and the
British Medical Journal
showing that the odds are 3.6 to 4 times greater that commercially sponsored studies will favor the sponsor’s product than studies without commercial funding. And in August of 2003 a study published in JAMA found that among
the highest-quality clinical trials
, the odds that those with commercial sponsorship will recommend the new drug are 5.3 times greater than for studies funded by nonprofit organizations. The authors noted that the lopsided results of commercially sponsored research may be “due to biased interpretation of trial results.” They cautioned that readers should “carefully evaluate whether conclusions in randomized trials are supported by data.” In other words, doctors are warned that the conclusions of even the best research published in the best journals
cannot
be taken at face value: Caveat lector—let the reader beware. This is the sorry state of the “scientific evidence” on which medical practice is based in the United States today.

Although many doctors have a gut feeling that there is a pro-industry bias in the scientific evidence that guides their care, almost all of the information that comes their way, including the opinions of the experts they trust, reinforces the validity of this “knowledge.” Plus, the findings are made to appear so overwhelmingly compelling and contain such enormous hope to provide ever more effective care to their patients that it is hard not to be a believer. There is a magical quality to all this progress that causes us to suspend our better judgment and seduces us into believing that what we are hearing and seeing is really true.

The techniques used
by world-class magicians are nearly impossible to spot, but once their methods are exposed, the magic quickly fades. The rest of this chapter explores the techniques used by the most talented masters of commercial medicine to brilliantly skew and slant their findings in the production of their “scientific” illusions.

After new drugs and medical devices are introduced to the market, the manufacturers go to great lengths to convince health care professionals that their products should be used for an ever-expanding range of symptoms. The case for implantable defibrillators is a perfect example. A patient of mine, Mr. Peters, is a 78-year-old easygoing retired mechanic who has been living alone since his wife passed away. A few years ago he was hospitalized for what turned out to be a small heart attack. While he was resting peacefully in his hospital bed, without warning his heart suddenly went into ventricular fibrillation (a rapidly fatal arrhythmia in which the heart’s ventricular contractions become chaotic and ineffective). The nurses saved his life by responding to the alarm set off by his heart monitor, immediately initiating cardiopulmonary resuscitation (CPR) and successfully shocking his heart back into a normal rhythm with defibrillator paddles applied to his chest.

The risk of this lethal arrhythmia recurring over the next two years was high, making Mr. Peters a perfect candidate for an implantable cardiac defibrillator. Just like U.S. Vice President Cheney, Mr. Peters had a defibrillator—an electrical device slightly smaller than a pack of cigarettes—surgically inserted underneath the skin of his chest.

About two months later, Mr. Peters was standing in his kitchen when, with absolutely no warning, he was suddenly knocked to the floor. Lying there, he realized that the jolt must have come from the cardiac defibrillator, and indeed, the recorder built into the device showed that his heart had once again gone into ventricular fibrillation. This episode probably would have been fatal without the defibrillator. When Mr. Peters told me this story, he was clearly grateful that his life had been saved by the device. And he chuckled about having been knocked to the floor.

The
cost of the defibrillator
is another story—about $25,000 for the device and another $5,000 to $15,000 for the doctor and hospital charges. Medicare covers the costs, and the therapy is, literally, lifesaving. But the number of people who survive ventricular fibrillation to become candidates for implantable defibrillators is limited. After its initial success with patients such as Mr. Peters, Guidant, the manufacturer, set its sights on a much larger group of patients.

Guidant
turned its attention to the 400,000 Americans
whose hearts are weakened each year by heart attacks, but who, unlike Mr. Peters, have not experienced life-threatening disturbances of their heart rhythm. These patients have a much higher risk of dying than do heart attack victims whose hearts remain strong: about 20 percent die in the 20 months following their heart attacks. Guidant hit a grand slam when a study was published in the NEJM showing a significant benefit of implanted defibrillators in this population. The patients who were randomly assigned to receive a defibrillator had 31 percent less risk of dying over the next 20 months than the patients in the control group. The article concluded that “prophylactic implantation of a defibrillator [in patients with hearts weakened by heart attacks] improves survival and should be considered as a recommended therapy.”

On the surface, this appears to be the best of all worlds: private enterprise motivated by the prospect of greater earnings discovering new ways to save lives. But let’s look at the results of this study from a slightly different perspective. For the first nine months of the study there was no difference between the death rate in the people who got the defibrillator and those who did not. Over the next 11 months, 5.6 percent fewer people who received defibrillators died. Based on these results, if 1000 heart attack patients with weakened hearts received defibrillators, a total of 56 would be alive at the end of 20 months who would otherwise have died. The other 944 patients would derive no benefit. In fact, there would be a downside for them: for each life saved by the defibrillator, there would be one additional hospitalization for congestive heart failure among the people who got defibrillators, compared with the control group.

The cost per year of life saved? Between $1.1 and $1.5 million, without including the cost of the additional hospitalizations required for the people who developed congestive heart failure.
*
Though it may sound callous, around $100,000 per year of life saved is considered the upper limit of cost-effectiveness for routine medical interventions. Although this number may be drifting upward as new, more expensive technologies are introduced, more than $1 million per year of life saved is clearly a staggering sum for any nation, even the richest in the world.

The NEJM article failed to mention that there is good evidence that there are other, much less expensive ways to prevent many more deaths among these high-risk patients. Only three years before the NEJM study,
Circulation,
the journal of the American Heart Association, published an article in which
a group of Italian researchers
looked at the effects of exercise training on a similar group of people with weakened hearts. This study randomized patients to receive either exercise training three times a week for eight weeks and then twice a week for one year, or to be in the control group and receive no exercise training. The results were dramatic: The risk of death was reduced by 63 percent in the exercise group (more than twice the benefit of the defibrillator); the risk of hospitalization for congestive heart failure went down by 71 percent (instead of up by 33 percent in the patients who received implanted defibrillators); and both exercise capacity and quality of life improved significantly in the exercise group and remained improved for the 40 months of the study (
p
< .001 for both).

The patients in this study were
not exactly the same as those in the defibrillator study
, but they did have similar mortality rates (about 20 percent per 20 months for the control groups). In absolute terms, twice as many lives were saved by exercise (22.8 percent over 40 months) as were saved by implanted defibrillators (5.6 percent over 20 months).

The study sponsored by Guidant made no mention of changes in exercise capacity and quality of life in the heart attack patients who received implanted defibrillators. Nor did it reference the Italian study in
Circulation
showing the dramatic benefits of exercise in a similar population of patients.

There is another effective and inexpensive tool to help these patients that was overlooked: smoking cessation. Eighty percent of the patients in the defibrillator study were either “current or former smokers.” How many of those patients were still smoking? The NEJM article does not tell us, but we do know from a review article in the
Archives of Internal Medicine
that
smoking cessation after heart attack
is associated with 1.5 to 2 times as much benefit as a defibrillator. The NEJM article reporting the benefits of implanted defibrillators did not venture beyond the interests of the study’s sponsor; there was no mention of exercise, smoking cessation, or other lifestyle changes.

While there were no technical violations in Guidant’s defibrillator study, sleight of hand was at work: the study was presented as if its purpose were to determine the best treatment for heart attack patients with weakened hearts. Closer inspection suggests that its real purpose was to create scientific evidence that would support sales of Guidant’s product. The study of defibrillators could easily have been designed to include lifestyle interventions, but, like the vast majority of commercially sponsored studies, it didn’t. Such a study might well have shown that defibrillators do play a role in the optimal treatment of some heart attack patients with weakened hearts. If so, that finding would have provided invaluable information to doctors. Instead, we are left not knowing the appropriate role of this potentially remarkable device in post–heart attack patients. Such research issues will not be addressed by the drug and medical-device companies as long as sales are rolling along. Why would the company that makes implantable defibrillators risk doing a study that might show that lifestyle changes were more effective than its expensive devices? That’s not its job.

The first step in a clinical trial is to decide what the drug or medical device will be compared with. The researchers then decide upon the doses for both the new and comparison drug(s). Companies can design studies in which the doses of the drugs being compared are not equivalent.

For example, Nexium, the “purple pill” for gastroesophageal reflux disease (GERD), is chemically almost identical to
the acid-blocking drug Prilosec
. Both are manufactured by AstraZeneca. In 2001, the patent was about to expire on Prilosec. This basically means that a drug’s “recipe” enters the public domain, and other companies can manufacture generic equivalents of it that sell for a small percentage of the price of the brand-name drug. So AstraZeneca sponsored
“head-to-head” studies between Prilosec and Nexium
, whose patent would remain in effect for several more years. One such study, done at the Cleveland Clinic, concluded that Nexium “demonstrates significantly greater efficacy than [Prilosec] in the treatment of GERD patients with erosive esophagitis.” It sounds as though doctors should abandon Prilosec and start prescribing the newer Nexium. The catch is that the dose of Nexium used in the study was 40 mg, but the dose of Prilosec was only half of that.
Would 40 mg of Prilosec daily
work as well as 40 mg of Nexium daily? The drug company never bothered to find out. Does 20 mg of Nexium work better than 20 mg of Prilosec? Not according to AstraZeneca’s own research. Nonetheless, Nexium 20 mg costs $4.90 per dose, while Prilosec 20 mg without a prescription costs about one-eighth as much.