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<DIV class=timestamp>May 9, 2007</DIV>
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<H1><NYT_HEADLINE type=" " version="1.0">Doctors Reap Millions for Anemia Drugs
</NYT_HEADLINE></H1><NYT_BYLINE type=" " version="1.0"></NYT_BYLINE>
<DIV class=byline>By <A title="More Articles by Alex Berenson"
href="http://topics.nytimes.com/top/reference/timestopics/people/b/alex_berenson/index.html?inline=nyt-per">ALEX
BERENSON</A> and <A title="More Articles by Andrew Pollack"
href="http://topics.nytimes.com/top/reference/timestopics/people/p/andrew_pollack/index.html?inline=nyt-per">ANDREW
POLLACK</A></DIV><NYT_TEXT></NYT_TEXT>
<DIV id=articleBody>
<P>Two of the world’s largest drug companies are paying hundreds of millions of
dollars to doctors every year in return for giving their patients <A
title="Recent and archival health news about anemia."
href="http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/anemia/index.html?inline=nyt-classifier">anemia</A>
medicines, which regulators now say may be unsafe at commonly used doses. </P>
<P>The payments are legal, but very few people outside of the doctors who
receive them are aware of their size. Critics, including prominent <A
title="Recent and archival health news about cancer."
href="http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/cancer/index.html?inline=nyt-classifier">cancer</A>
and kidney doctors, say the payments give physicians an incentive to prescribe
the medicines at levels that might increase patients’ risks of heart attacks or
strokes. </P>
<P>Industry analysts estimate that such payments — to cancer doctors and the
other big users of the drugs, kidney dialysis centers — total hundreds of
millions of dollars a year and are an important source of profit for doctors and
the centers. The payments have risen over the last several years, as the makers
of the drugs, <A title="More information about Amgen Inc."
href="http://topics.nytimes.com/top/news/business/companies/amgen_inc/index.html?inline=nyt-org">Amgen</A>
and <A title="More information about Johnson & Johnson"
href="http://topics.nytimes.com/top/news/business/companies/johnson_and_johnson/index.html?inline=nyt-org">Johnson
& Johnson</A>, compete for market share and try to expand the overall
business.</P>
<P>Neither Amgen nor Johnson & Johnson has disclosed the total amount of the
payments. But documents given to The New York Times show that at just one
practice in the Pacific Northwest, a group of six cancer doctors received $2.7
million from Amgen for prescribing $9 million worth of its drugs last year. </P>
<P>Yesterday, the <A
title="More articles about the U.S. Food And Drug Administration."
href="http://topics.nytimes.com/top/reference/timestopics/organizations/f/food_and_drug_administration/index.html?inline=nyt-org">Food
and Drug Administration</A> added to concerns about the drugs, releasing a
report that suggested that their use might need to be curtailed in cancer
patients. The report, prepared by F.D.A. staff scientists, said no evidence
indicated that the medicines either improved quality of life in patients or
extended their survival, while several studies suggested that the drugs can
shorten patients’ lives when used at high doses. Yesterday’s report followed the
F.D.A.’s decision in March to strengthen warnings on the drugs’ labels. </P>
<P>The report was released in advance of a hearing scheduled for tomorrow,
during which an F.D.A. advisory panel will consider whether the drugs are
overused.</P>
<P>The medicines — Aranesp and Epogen, from Amgen; and Procrit, from Johnson
& Johnson — are among the world’s top-selling drugs, with combined sales of
$10 billion last year. In this country, they represent the single biggest drug
expense for Medicare and are given to about a million patients each year to
treat anemia caused by kidney disease or cancer <A
title="Recent and archival health news about chemotherapy."
href="http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/chemotherapy/index.html?inline=nyt-classifier">chemotherapy</A>.</P>
<P>Dr. Len Lichtenfeld, the deputy chief medical officer of the <A
title="More articles about American Cancer Society"
href="http://topics.nytimes.com/top/reference/timestopics/organizations/a/american_cancer_society/index.html?inline=nyt-org">American
Cancer Society</A>, said that both patients and doctors would benefit from
fuller disclosure about the payments and the profits that doctors can make from
them. “I suspect that Medicare is going to take a very careful look at what is
going on here,” he said.</P>
<P>Still, the anemia drugs can help patients’ quality of life, when used
appropriately, he said. “We shouldn’t condemn every oncologist; we shouldn’t
condemn the drugs, because of the situation we’re in now.”</P>
<P>Federal laws bar drug companies from paying doctors to prescribe medicines
that are given in pill form and purchased by patients from pharmacies. But
companies can rebate part of the price that doctors pay for drugs, like the
anemia medicines, which they dispense in their offices as part of treatment. The
anemia drugs are injected or given intravenously in physicians’ offices or
dialysis centers. Doctors receive the rebates after they buy the drugs from the
companies. But they also receive reimbursement from Medicare or private insurers
for the drugs, often at a markup over the doctors’ purchase price. </P>
<P>Medicare has changed its payment structure since 2003 to reduce the markup,
but private insurers still often pay more. Combined with those insurance
reimbursements, the rebates enable many doctors to profit substantially on the
medicines they buy and then give to patients.</P>
<P>The rebates are related to the amount of drugs that doctors buy, and
physicians that agree to use one company’s drugs exclusively typically receive
higher rebates.</P>
<P>Johnson & Johnson said yesterday in a statement that its rebates were not
intended to induce doctors to use more medicine. Instead, the rebates “reflect
intense competition” in the market for the drugs, the company said.</P>
<P>Amgen said that rebates were a normal commercial practice and that it had
always properly promoted its drugs. </P>
<P>“Amgen is dedicated to patient safety,” said David Polk, a spokesman. “We
believe our contracts support appropriate anemia management and our product
promotion is always strictly within the label.”</P>
<P>Both companies’ stocks fell yesterday after release of the F.D.A. report.
Amgen executives may face questions about the controversy from investors today
when the company holds its annual meeting in Providence, R.I. </P>
<P>Since 1991, when the first of the drugs was still relatively new, the average
dose given to dialysis patients in this country has nearly tripled. About 50
percent of dialysis patients now receive enough of the drugs to raise their red
blood cell counts above the level considered risky by the F.D.A. </P>
<P>American patients receive far more of the anemia drugs than patients
elsewhere, with dialysis patients in this country getting doses more than twice
as high as their counterparts in Europe. Cancer care shows a similar pattern.
American cancer patients are about three times as likely as those in Europe to
get the drugs, and they receive somewhat higher doses.</P>
<P>The rebates inevitably encourage use of the drugs, said Michael Sullivan, who
for nine years worked as a business manager for the group of six cancer doctors
in the Pacific Northwest, before losing his job last year. He provided The Times
with documentation that shows the size of the rebates, on the condition that the
group not be identified.</P>
<P>“Personally, I think rebates should go away,” said Mr. Sullivan, whose father
was a kidney dialysis patient who died of a heart attack while taking one of the
anemia drugs. “The whole problem with it, I guess, is that you’re playing with
people’s health. It’s not the same as buying widgets.”</P>
<P>For doctors who use less of the drugs, the rebates may make the difference
between losing money on the drugs or breaking even. Mr. Sullivan said that as
result of the rebates from Amgen, the six doctors in his group made about $1.8
million in net profit on the drugs they prescribed. </P>
<P>Unlike most drugs, the anemia medicines do not come in fixed doses.
Therefore, doctors have great flexibility to increase dosing — and profits.
Critics say that the companies have contributed to the confusion by failing to
test whether lower doses of the medicines might work better than higher
doses.</P>
<P>“The burden of proof is for companies and industry to demonstrate that a drug
is safe at a certain level,” Dr. Ajay Singh, an associate professor at Harvard
Medical School. Dr. Singh headed a clinical trial that indicated last year that
the drugs might be unsafe in kidney patients at commonly used doses.</P>
<P>Known generically as epoetin and darbepoetin, and often referred to simply as
EPO, the drugs are genetically engineered versions of a human protein that
stimulates the bone marrow to produce more red blood cells and increase the
body’s ability to carry oxygen.</P>
<P>Most doctors and patients agree the drugs are very helpful for patients when
used to correct severe anemia, which can be debilitating and even
life-threatening. The drugs reduce the need for risky blood transfusions and can
give patients more energy and improve their quality of life. </P>
<P>“We have transformed the lives of patients with chronic kidney disease,” said
Dr. Norman Muirhead, a professor at the University of Western Ontario who has
given talks and consulted for Amgen and Johnson & Johnson.</P>
<P>But there is little evidence that the drugs make much difference for patients
with moderate anemia, and federal statistics show that the increased use of the
drugs has not improved survival in dialysis patients. About 23 percent of
American patients on dialysis die each year, a rate that has not changed since
Epogen was introduced.</P>
<P>Anemia is measured by a patient’s level of hemoglobin, the molecule the body
uses to transport oxygen to its cells. Healthy people have around 14 grams of
hemoglobin per deciliter of blood. Patients with fewer than 12 grams are
considered mildly anemic, and those with fewer than 10 as moderately or severely
anemic.</P>
<P>The labels on the drugs, as currently approved by the F.D.A., encourage
doctors to aim for a hemoglobin level of 10 to 12. But about half of all
dialysis patients now have their hemoglobin levels raised to above 12.</P>
<P>Critics of the drugs say their increased use has been driven by profit.
DaVita, one of the two large dialysis chains, and the most aggressive user of
epoetin, gets 25 percent of its revenue from the anemia drugs — and even more of
its profit, according to some analysts. </P>
<P>Dr. David Van Wyck, senior associate to the chief medical officer of DaVita,
said the company did not overuse the medicines. </P>
<P>Doctors determine how much to use, Dr. Van Wyck said. “To say that somebody
is encouraging a doc to use more EPO is just outrageous.” </P>
<P>Although the safety debate has heated up only recently, the first sign that
the drugs might be dangerous came more than a decade ago. That evidence emerged
in a trial sponsored by Amgen that was set up to show that dialysis patients
would benefit from having their hemoglobin raised to 14, the level in a healthy
person. </P>
<P>But the trial, which was stopped in 1996, found that patients in that group
had more deaths and heart attacks than a group treated with a hemoglobin goal of
10. </P>
<P>That trial should have discouraged doctors from using too much epoetin and
encouraged Amgen to study the risks further, said Dr. Steven Fishbane, a
nephrologist at Winthrop-University Hospital on Long Island.</P>
<P>Instead, use of epoetin continued to soar. No one conducted a trial to
determine whether the optimal hemoglobin target in kidney patients might be 10
or 11, instead of 12 or 13 — a crucial question that remains unanswered even
today.</P>
<P>Dr. Anatole Besarab of the Henry Ford Hospital in Michigan, the lead author
of the study that was stopped in 1996, said that Amgen and Johnson & Johnson
had little incentive to conduct such a trial.</P>
<P>Dr. Robert M. Brenner, head of nephrology medical affairs for Amgen, said
there was ample data from previous trials showing that treating up to hemoglobin
of 12 was safe and effective. </P>
<P>Some hospitals and doctors have used epoetin more conservatively than the big
dialysis chains. </P>
<P>Dr. Ronald A. Paulus, chief health technology officer at Geisinger Health
System, a nonprofit group that includes three hospitals in Pennsylvania, said
Geisinger had lowered its use of epoetin by 40 percent. Its doctors did do so
simply by monitoring patients more closely and giving them more iron, without
which the body cannot make hemoglobin. </P>
<P>Dr. N. D. Vaziri, the chief of nephrology at the <A
title="More articles about the University of California."
href="http://topics.nytimes.com/top/reference/timestopics/organizations/u/university_of_california/index.html?inline=nyt-org">University
of California</A>, Irvine, said some clinics had been too aggressive about
giving extremely high doses of epoetin to people who did not initially respond
to lower levels. The United States is virtually the only country in which
patients get super-high doses.</P>
<P>“You create a toxicity situation,” said Dr. Vaziri, who has done studies in
animals showing how epoetin contributes to <A
title="Recent and archival health news about blood pressure."
href="http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/bloodpressure/index.html?inline=nyt-classifier">hypertension</A>
and blood clots. </P>
<P>In cancer patients, concerns were raised in 2003 by clinical trials meant to
show that raising hemoglobin to high levels would make chemotherapy or <A
title="Recent and archival health news about radiation."
href="http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/radiation/index.html?inline=nyt-classifier">radiation</A>
therapy more effective. Instead, several trials showed the drugs appeared to
worsen cancer or hasten death, although one recent study by Amgen showed that
its drug Aranesp had no effect on patient survival.</P>
<P>The conflicting studies are among the issues the F.D.A. advisory committee is
expected to discuss tomorrow. Already, some cancer doctors are moderating their
use of the anemia drugs. </P>
<P>Dr. Peter Eisenberg, an oncologist in Marin County, Calif., said many doctors
had been induced to use more epoetin by the financial incentives and the belief
that the drug was helpful. </P>
<P>“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.</P>
<P>“Now it’s much scarier than that,” he said. “We could really be doing harm.”
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