07/09/2007 07:54 pm ET | Updated May 25, 2011

What Happens When a Heavily-Advertised Drug Harms?

This hasn't been a good year for Amgen or Johnson & Johnson, which make various forms of EPO, the biotech wonder drug that raises red blood cell counts (as every dope-taking Tour de France bicyclist knows). Clinical trials have shown that they can increase the risk of heart attacks and strokes in dialysis patients, whose failing kidneys don't produce enough natural erythropoietin; and, they hasten death for some cancer patients with solid tumors when the drugs are excessively used to alleviate chemotherapy-related anemia. (You've seen the ads: "Are you ready for chemo yet?")

The Food and Drug Administration in May determined that the "dear doctor" letters sent out by the companies in January didn't go far enough. It slapped a black box warning on the drugs, which are sold under the Aranesp, Epogen and Procrit labels. The agency also convened an oncologic drugs advisory committee meeting where one attending physician, after reviewing the evidence, expressed concern that the drugs might be "Miracle-Gro for cancer."

In mid-May, the Center for Medicare and Medicaid Services (CMS), which foots the tab for most EPO use (dialysis is paid for by Medicare and most cancer patients are over 65), decided to scale back its payments when the drugs are used for cancer. While the policy was announced shortly after the FDA advisory committee meeting, it had been in the works for nearly a year and was accompanied by an exhaustive review of the medical literature, notable for its lack of completed trials. Still, the evidence suggested:

Emerging data suggest that ESA use may be associated with increased morbidity and mortality in a variety of patient populations despite the alleviation of anemia. Although the features and exact mechanisms of the increased mortality require better delineation, both thrombo-embolic-vascular disease and tumor progression appear to be involved.

It didn't take long for the EPO empire to strike back.

Last week, Senators Kent Conrad (D-SD) and Thad Cochran (R-MS) circulated a letter on Capitol Hill for other senators to sign. It clearly echoed talking points written by Amgen and J&J lobbyists in urging CMS to "carefully consider the public health consequences of this proposed coverage decision." The letter warned that the CMS proposal will raise demand for transfusions from the nation's limited blood supply and negatively affect the quality of life of the nation's cancer patients.

The emerging data that these drugs when used off-label were probably killing people didn't get mentioned in the letter. Indeed, the fact that EPO use in cancer patients is largely off-label and may be "inappropriate" doesn't appear until the fifth paragraph of the senators' 7-paragraph letter, and even then it is raised as part of these senators' admonition to CMS's leaders that the agency's safety concerns should not be used to limit patients' access to "appropriate care."

The senators are not alone. Similar letters have been sent to CMS by the American Society of Clinical Oncologists and the Community Oncology Alliance, whose members earn large profits from infusing patients with EPO in their offices, a system that a New York Times editorial appropriately labeled a kickback scheme. Company discounts are based on how much EPO doctors use (see this GoozNews, which commented on an early May New York Times story documenting the system).

The details of the CMS decision are complex, but reduced to their essence, the agency fears raising red blood cell counts too soon, too quickly and to near normal levels does more harm than good. When the new rule goes into effect, CMS will not reimburse physicians for EPO use in cancer patients with solid tumors unless their hemoglobin level falls below 9 grams per deciliter of blood (a hematocrit of 27). It will also limit treatment to 12 weeks per year and eliminate EPO use for certain conditions, including vitamin deficiency, radiation-induced anemia and when patients have uncontrolled hypertension.

The agency also wants to eliminate its use in myelodysplasia, a form of leukemia. That suggestion drew heated protests from the patient community that suffers from the disease and the doctors who treat them. There is evidence in the literature that they benefit from EPO use because of their need for frequent transfusions. Not surprisingly, the senators and oncology groups emphasized that condition in their letters.

The CMS draft decision memo probably needs some adjustments. Perhaps myelodysplasia should be taken off the list. Perhaps the cap on weeks of treatment should be related to the number of times a person gets chemo during the year, since that varies from cancer to cancer.

But the last thing CMS needs is pressure from Capitol Hill to roll back the larger intent of the proposed payment policy. What the agency needs instead is legislative support for its efforts to help doctors obey the initial injunction of all medical practice - "First, do no harm."

The evidence is rapidly mounting that the hypermarketing of these drugs by Amgen and J&J, aided and abetted by CMS payment policy, encouraged oncologists to disobey that cardinal rule. It needs to end now, and the best way to do that is by cutting off the mother's milk of medical misfeasance: payments for inappropriate use.