At a December 6, 2006 hearing of the House Ways and Means Committee, then chairman Bill Thomas (R-CA), told Leslie Norwalk, acting commissioner of the CMS, "we have a payment policy that perhaps is killing people; and we are using $2 billion, the highest price paid in a relatively narrow area for the use of the drug through the payment policy, that may in fact be doing that."
Studies have shown that the massive off-label marketing of these drugs has definitely resulted in many deaths, but the question that remains is how many.
The drugs at issue include Aranesp, the brand name for darbepoetin, and Epogen and Procrit, the brand names for epoetin. Amgen manufactures all three drugs, but Ortho Biotech Products, a Johnson & Johnson subsidiary markets Procrit.
They are top money-makers for both companies. In 2006, ESA's combined had sales of nearly $10 billion, and Aranesp and Epogen accounted for $6.63 billion, or 48% of Amgen's total $14.3 billion revenue in 2006.
The drugs belong to a class known as Erythropoiesis Stimulating Agents (ESAs), which are man-made versions of a hormone normally produced in the kidneys to stimulate bone marrow cells to produce hemoglobin which is the main component of red blood cells.
The severity of anemia is determined by a patient's hematocrit, the proportion of red blood cells in whole blood, which should remain at between 33% and 36%, according to the FDA. The labeling for ESAs specifies that patients should have a hemoglobin level no higher than 12 grams per deciliter of blood.
ESAs are approved only to treat anemia and reduce the need for blood transfusions in patients with chronic kidney failure undergoing dialysis, patients with cancer who are receiving chemotherapy, patients scheduled for major surgery, and HIV patients with anemia due to zidovudine therapy.
However, they are being administered off-label to kidney patients who are not receiving dialysis, cancer patients who are not undergoing chemotherapy and in doses that result in higher levels of hemoglobin than are approved by the FDA as safe and effective.
On March 9, 2007, the FDA announced that all ESAs must carry black box warnings on their labels about the increased risk for serious side effects, including death, and advised doctors that they should use the lowest dose necessary to avoid the need for blood transfusions caused by anemia.
Several recent reports have shown that dialysis centers are administering higher doses of ESAs which has resulted in an increased rate of stroke, heart attack and death in dialysis patients. The dosage received by the typical dialysis patient in the US has nearly tripled since the early 1990s, according to the November 16, 2006, New York Times.
A paper presented at the annual conference of the American Society of Nephrology[,] reported that 37% of patients at Davita clinics, the second largest provider of dialysis in the US, had hemoglobin levels higher than 14 grams at least one time in a 9-month period.
Dialysis patients in the US are dying at a higher rate due to this drugging-for-profit scheme. In Europe, where lower doses of ESAs are given, the Times reports that, about 15% of dialysis patients die each year compared to 22% in the US.
Dialysis centers are also boosting profits by administering the drugs intravenously instead of by injection. According to the Boston Globe on October 24, 2006, clinics would use 30% less ESAs, at a potential savings of $375 million each year, if ESAs were injected because the method require a lower dose and they stay in the system longer.
Critics blame the over-use on the financial incentives in Medicare reimbursement policies. Medicare covers medical care for patients with End Stage Renal Disease, and between 1998 and 2003, spending for ESRD patients increased nearly 50%. About $64,000 a year is spent for each dialysis patient, according to US Renal Data System.
Medicare guarantees dialysis centers a 6% profit for administering ESAs, and in April 2006, the CMS drew fire from Capitol Hill when it adopted a policy allowing payment for the administration of ESAs until hematocrits reached 39%.
The Ways and Means Committee chairman, Rep Thomas, sent a letter chastising Mark McClellan, the CMS Administer at the time, asking why CMS had not developed a policy to deal with the out-of-control dosing of patients at a higher levels. "I cannot understand why CMS would knowingly contradict FDA findings," he wrote.
The CMS did not respond to the letter, so in November 2006, incoming chairman of the Committee, Rep Pete Stark (D-CA), and Rep Thomas sent a another letter to acting CMS Administrator Leslie Norwalk, describing the CMS policy as "a reimbursement incentive for providers to continue to increase doses" past the approved level.
Ms Norwalk did not respond to that letter either, but on December 6, 2006, Ms Norwalk and specific experts were called to testify at a Committee hearing due to "growing concern about unsafe and questionable treatment for Medicare's coverage for kidney failure, also known as End Stage Renal Disease," Rep Thomas said.
Through the current rules which endorse expanding reimbursement to allow hematocrit to be targeted to any level, Thomas said, CMS has implemented a policy harmful to its beneficiaries that will cost hundreds of millions of dollars in additional expenditures.
During the questioning of Ms Norwalk, it was revealed that the Monitoring Policy Group, created by the CMS, approved the higher hematocrit guidelines, and two-thirds of the members had financial ties to either Amgen, Johnson & Johnson or the dialysis clinics that profit by selling more of the drugs.
"Now what troubles me is that of the 24 members," Rep Stark told Ms Norwalk, "18 of them disclosed financial associations with Amgen or Johnson & Johnson."
It was also noted that the National Kidney Foundation guidelines had raised the hemoglobin limit to 13. However, a clue as to how that came about surfaced a few months later on March 21, 2007, when the New York Times reported that the president of the Foundation, Dr Allan Collins, was also the director of the Minneapolis-based Medical Research Foundation and in 2004, the year he was made president, Amgen underwrote more than $1.9 million worth of research and education programs led by Dr Collins, and paid him at least $25,800 in mostly consulting and speaking fees in 2005.
Dr Laura Pizzi, a professor at Jefferson Medical College, testified as lead author on a study in the November 2006, Dialysis and Transplantation journal, conducted to determine to what extent health care providers were adhering to clinical guidelines for patients receiving dialysis.
She said the study found significant overuse of the drugs, and although the researchers were not surprised to see that providers were not strictly adhering to the guidelines, they were surprised by the extent to which ESA use deviated from the recommendations.
When converting the increased use to dollar amounts based on Medicare reimbursement rates in 2005, Dr Pizzi said the population with a red blood cell count above industry guidelines had higher drug costs of $3,100 per patient each year.
"We estimate that CMS," she told the panel, "could have reduced expenditures for these drugs by 36 percent if dialysis facilities adhered to the guidelines."
If CMS spends $2 billion a year, she said, "it is reasonable to say that several hundred million dollars could have been saved if the providers followed the guidelines."
Dr Noshi Ishak, a kidney specialist who owns a dialysis clinic in Laconia, NH addressed the huge profits of administering ESA's intravenously instead of by injections.
He said he switched to administering the drugs by injection in 1998 and usage dropped by more than 20%, or equivalent "to $3,120 savings per patient per year for Medicare."
The FDA's Oncology Drugs Advisory Panel is scheduled to meet on May 10, 2007, to review the safety and effectiveness of ESAs, and lawmakers have ordered Amgen and J&J to cease all direct-to-consumer advertising and physician incentives until the FDA determines whether measures need to be taken to protect the public from these products.