From the Moss Reports Newsletter http://www.cancerdecisions.com/052707.html

CANCER DOCTORS ARE PAID TO PRESCRIBE DUBIOUS DRUGS - PART II

(Last week, I began a two-part discussion of the class of drugs called epoetins, or erythropoiesis stimulating agents (ESAs), which are widely used in the treatment of cancer-related anemia. I conclude that discussion, with references, this week.)

Double Dipping

Drug company kickbacks to doctors who prescribe epoetins such as Aranesp, Procrit and Epogen total hundreds of millions of dollars per year and are considered an important source of income for oncologists. "The payments have risen over the last several years," said an article in the New York Times, "as the makers of the drugs, Amgen and Johnson & Johnson, compete for market share and try to expand the overall business."

Illustrating the scope of the problem, just one group of six oncologists in the Pacific Northwest received $2.7 million from Amgen alone for prescribing $9 million worth of its drugs last year (2006). Thus, doctors pocketed about one-third of the gross cost of the drugs in hush-hush rebates from the companies.

But doctors actually get paid two ways for using these drugs. Although Federal law bans drug companies from paying doctors to prescribe medicines given in pill form and purchased by patients from pharmacies, companies are allowed to rebate part of the price that doctors themselves pay for drugs such as the epoetins, which are then dispensed in their offices as part of treatment. Doctors receive their rebates after they buy the drugs directly from the manufacturer. They also receive reimbursement from insurance companies or Medicare for the drugs, often at a markup over the doctors' purchase price. While Medicare in 2003 changed its payment structure, private insurers generally continue to pay more. Needless to say, when such payments are combined with the aforementioned rebates, it adds considerably to oncologists' salaries.

The size of rebates is related to the quantity of drugs that the doctors buy. Rebates increase if doctors also agree to use one company's drugs exclusively. Johnson & Johnson said in a statement that the rebates were not intended to induce doctors to use more medicine, but simply "reflect intense competition" in the market for the drugs. "Amgen is dedicated to patient safety," said David Polk, a spokesman for that company. "We believe our contracts support appropriate anemia management and our product promotion is always strictly within the label." But the Times notes that American cancer patients are about three times as likely as those in Europe to get these drugs. US patients also receive higher doses.

As a result of the rebates from Amgen, six US doctors alone made about $1.8 million in net profit on the drugs they prescribed. Doctors have great flexibility in the amount of any drug they prescribe and in the profits they derive, and so there is little to stop them from using higher doses and thereby garnering higher rebates. The companies in question have generally failed to test whether or not lower doses of the medicine might work as well as these higher doses. In the period 2002-2003, for instance, the average EPO dose per week for an American patient was 17.4 thousand units compared to 10.8 in Canada, 8.0 in Britain, 6.8 in Germany and 5.3 in Japan. In addition, while 32 percent of American patients received doses over 18,000 units per week, only 1 percent of German patients did so.

Dr. Ajay Singh, an associate professor at Harvard Medical School, headed a clinical trial that indicated last year that the drugs might be unsafe in kidney patients at commonly used doses. "The burden of proof is for companies and industry to demonstrate that a drug is safe at a certain level," Singh said. Although epoetins were shown to be unsafe as far back as 1996, their use has continued to soar.

Dr. Ronald A. Paulus of Geisinger Health System of Pennsylvania said the three-hospital chain had lowered its use of epoetins by 40 percent. It did this by monitoring patients closely and by the simple expedient of giving patients supplemental iron when necessary, in order to support the body's ability to make hemoglobin. An iron supplement costs pennies per day. (Nevertheless, cancer patients should NOT self-medicate with iron supplements. Such supplements can be toxic and can actually encourage the growth of cancer in some situations. The decision to supplement with iron should only be made by an experienced medical professional.)

Further concerns were raised in 2003 by clinical trials that were meant to show that raising hemoglobin to high levels would make chemo- or radiation therapy more effective. Instead, the trials showed that epoetin usage was capable of accelerating patients' cancer, and may in some cases have been associated with shorter survival, although a recent study financed by Amgen claimed that Aranesp had no effect on patient survival. At the May 10th meeting of the FDA Advisory panel one of the members asked company representatives, "What data do you have to assure me that this is not Miracle-Gro for cancer?"

Dr. Peter Eisenberg, a Marin County oncologist, said that many doctors had been induced to use more epoetins by the financial incentives the company offered, as well as their belief that these drugs were helpful.

"The deal was so good," he said. "The indication was so clear and the downside was so small that docs just worked it into their practice easily. Now it's much scarier than that," he said. "We could really be doing harm."

The Times' excellent articles on the subject have sparked widespread revulsion and outrage. There are at this writing over 200 reader comments at the Times Web site alone. A few doctors have written to say that they had already changed their prescribing practices before the Times' latest revelations and to assure readers they did not personally profit from the use of the drug. But that does not change the fact that the rebate program continues apace, and is apparently widespread. More typical responses are that it is "scary" and "disgusting" for physicians to profit from a potentially dangerous treatment in this way.

As long as oncologists continue to derive a considerable amount of their income from drug company rebates of this kind, their clinical judgment will be suspect. Cancer patients will have no way to know whether a particular drug is being prescribed because it is the right and proper treatment or because it lines the pockets of the doctor who gives it. Oncologists whose prescribing habits are influenced by potential personal gain are engaging in unprofessional behavior, since they are putting their own financial interests above the well-being of their patients. Furthermore, even those who are not themselves deriving an income from the rebated sale of drugs, but who fail to speak out against the practice, are guilty of enabling their more greedy colleagues.

All in all, it is an intolerable situation and FDA's recent warnings, while welcome, hardly make a dent in the overall problem.

--Ralph W. Moss, Ph.D.

References:

FDA Public Health Advisory: erythropoiesis-stimulating agents (ESAs). March 13, 2007. Available at:
http://www.fda.gov/cder/drug/advisory/RHE2007.htm

Berenson, Alex and Pollack, Andrew. Doctors reap millions for anemia drugs. New York Times, May 9, 2007. Available at:
http://www.nytimes.com/2007/05/09/business/09anemia.html?pagewanted=1

Birnbaum S. CT scanning: too much of a good thing. British Medical Journal 2007; 334(7601): 1006.

Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII - Phase 2 Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation, National Research Council available from the National Academies Press at:
http://www.nap.edu/catalog/11340.html

Jefford M, Tattersall MH. Informing and involving cancer patients in their own care. Lancet Oncology 2002;3(10):629-37.

Pollack, Andrew. F.D.A. panel seeks limits on cancer patient drugs. New York Times, May 11, 2007. Available at:
http://select.nytimes.com/mem/tnt.html?emc=tnt&tntget=2007/05/11/
health/11anemia.html&tntemail0=y