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HEALTH CARE

How Reducing Negligible Risks Drives Up Health Costs

A Closer Look at the Clinical Trials for Crestor

empty pill bottles with phrase over them: Is new better than old? SOURCE: iStockphoto, SP The over-prescription of statins is costing Americans billions, and the media is complicit with the problem. An independent national institute that compared the effectiveness of treatments could reduce unnecessary spending.

While President-elect Barack Obama’s health team, along with insurers and employers around the country, are working out why we pay so much for health care that provides little measurable benefit, one reason for those unnecessarily high costs recently made every evening news show and front page.

Bloomberg News announced, “AstraZeneca’s Crestor slashed the risk of heart attack, stroke and death by nearly half in people with normal or low cholesterol in a study, potentially opening a way to save the lives of thousands seemingly healthy people.” MSNBC News made the same announcement and then quoted the president of the American College of Cardiology: “This takes prevention to a whole new level.” Ron Winslow of The Wall Street Journal added, “The findings could substantially broaden the market for statins, the world’s best-selling class of medicines.” Except for USA Today, which worried about the high cost to patients, health plans, and the public, most announcements read like infomercials, excited about a major new market.

In short, this “pathbreaking” study that “takes prevention to a whole new level” actually offers little benefit and offsets it with a costly side effect.

These news headlines referred to a large clinical trial published on November 20th in the New England Journal of Medicine that purported to demonstrate the effectiveness of Crestor—even on older patients with low cholesterol who scored high on a test for CRP, or C-reactive protein. CRP levels are used as an imprecise indicator of heart disease, though the molecule is “a nonspecific marker for low-grade inflammation,” according to Dr. Bernadine Healy, an adviser to U.S. News and World Report.

Almost no one learned that the “slashed nearly in half” reduction in cardiovascular trauma was tiny, from 1.36 percent to 0.77 percent, a difference of just 0.59 percent.

And almost none of the stories reported that the people taking Crestor had a comparable increased risk (0.60 percent) of getting diabetes. Those that did said the increase was “small,” but then so was the reduction in cardiovascular events. Suppose newscasters announced, “Major study finds patients taking Crestor for systemic inflammation experience less than 1 percent reduction in cardiovascular events and an equal increase in diabetes”? In short, this “pathbreaking” study that “takes prevention to a whole new level” actually offers little benefit and offsets it with a costly side effect.

American medicine is rife with such commercial bandwagon tests, procedures, and drugs. An effective policy solution would involve the creation of a comparative effectiveness institute that offered independent evaluations and subjected treatments to head-to-head trials in order to make recommendations about which ones are actually worth the money. President-elect Barack Obama’s health care platform calls for such an entity, and in August, Senate Finance Committee Chair Max Baucus (D-MT) and Senate Budget Committee Chair Kent Conrad (D-ND) introduced the “Comparative Effectiveness Research Act,” legislation that would create a nonprofit institute.

The closer you look, the less beneficial this breakthrough looks. For example, the investigators had screened out 80 percent of their sample so that the trial included only patients with a high CRP but without 13 other prevalent health risks. Those 13 risks include a history of cardiovascular disease, diabetes, arthritis, high blood pressure, cancer, hypothyroidism, or substance abuse. Also excluded were people taking hormone replacement therapy or lipid-lowering therapy.

Put another way, the vast majority of older women and men with low cholesterol and high CRP were excluded because they had conditions that might weaken the results. The trial aimed to select just those people who were most likely to produce a dramatic result but establish the basis for everyone to take the test to see if they have high CRP. If they do, they probably have other risks or behaviors like those people screened out of the trial, so taking Crestor (the most expensive statin) might or might not increase their risk for diabetes and reduce their risk for cardiovascular trauma.

Only a few news stories noted vaguely that Crestor itself has serious side effects. Reports to the FDA of kidney problems from patients taking Crestor exceeded reports for all other statins combined and led The Health Research Group in Washington, D.C. to recommend it be taken off the market. Crestor also lowers levels of CoQ10, a compound that helps generate energy and maintain muscle (including the heart muscle). Fatigue and weakness can result.

Moreover, the trial was stopped with 3.1 years remaining, and it is during this later period of testing when adverse side effects are most likely to surface. Running trials long enough to record benefits but too short to record adverse effects is a common practice in company-sponsored trials. It is one reason why adverse side effects are now epidemic, the 4th leading cause of death, according to the Food and Drug Administration. As Professor Mark Hlatky at Stanford Medical School wrote in a cautious editorial, “Long-term safety is clearly important in considering committing low-risk subjects without clinical disease to 20 years or more of drug treatment.”

Currently, new drugs “just have to be better than nothing.”

The results of this market-driven trial were reported to the press in a way to get the public as well as the medical profession mobilized to generate large new revenues, thus making the media an agent of commercial interests. No mention was made of the fact that doctors are already prescribing statins to millions of patients to lower their cholesterol when in fact doing so does not reduce cardiovascular risk for those who have no other specific risk. The over-prescription of statins is costing everyone billions. Instead, the news emphasized how statins would now benefit millions more with low cholesterol.

The additional cost to the nation’s insurers, employers, and taxpayers of prescribing Crestor to patients with CRP is estimated to be $9.0-9.7 billion. The reduction of an already small risk would cost about $557,000 per life saved, according to James Stein at the University of Wisconsin School of Medicine and Public Health. That does not include the $80 for the patented CRP test that a much larger population would first have to take, nor the costs of treating new cases of diabetes and other side effects. Yet official guidelines for doctors appear likely to change and recommend the CRP test, whose patent is held by the principal investigator of the trial and his employer, Brigham and Women’s Hospital in Boston.

The main beneficiaries will be the patent-holders and AstraZeneca, the sponsor of the trial. Industry-sponsored trials are nearly 4 times more likely to produce results favorable to the sponsor’s product than independently funded trials, and this one is no exception.

In order to avert future misleading claims about new drugs and to help lower the costs of health care, the country needs an organization like the Comparative Effectiveness Research Institute proposed by Senators Baucus and Conrad. Their bill, S.3408, cosponsored with Senators Jeff Bingaman (D-NM) and Sheldon Whitehouse (D-RI), aims to control costs by improving the effectiveness of treatments used. It would have independent funding to assess the additional clinical benefit of new tests and interventions against their costs in order to get good value for our money.

Currently, new drugs “just have to be better than nothing,” according to Dr. David Barbe, chair of the American Medical Association Council on Medical Service. As Gail Shearer, the director of Consumer Reports’ Best Buy Drugs website and service said, “People are ready to talk about value.” The CRP-Crestor trial and bandwagon illustrates why an institute like this is a vital part of any health care reform under the new administration.

Donald W. Light is a professor of comparative health care at the University of Medicine & Dentistry of New Jersey and a senior fellow at the Center for Bioethics, University of Pennsylvania. His forthcoming book, The Risks of Prescription Drugs, will appear in bookstores this winter.

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