For-Profit Dialysis Centers Bigger Users of Epoietin Per Patient

April 17, 2007

BETHESDA, Md. -- Chains of for-profit dialysis centers use considerably more erythropoiesis-stimulating agents per patient than do non-profit or hospital-affiliated centers, regardless of anemia status, found investigators here.

BETHESDA, Md., April 17 -- Chains of for-profit dialysis centers bill Medicare for considerably more erythropoiesis-stimulating agents per patient than do non-profit or hospital-affiliated centers, regardless of anemia status, found investigators here.

Epoietin therapy for anemia in dialysis patients is the largest single drug expenditure under Medicare, and the higher use of epoietin (Epogen) and darbapoietin (Aranesp) in for-profit dialysis chains costs an additional ,700 per patient per year, according to Mae Thamer, Ph.D., from the Medical Technology and Practice Patterns Institute, here, and colleagues.

The differences in epoietin use between profit-driven standalone dialysis providers and other centers cannot be explained by patient characteristics such as severity of illness, or relative responsiveness to epoietin therapy, the authors wrote in the April 18 issue of Journal of the American Medical Association.

In an accompanying editorial, Daniel W. Coyne, M.D. of Washington University in St. Louis, asserted that "physicians need to challenge industries that appear to be using patients as profit centers based on bad science."

In March, the FDA warned that aggressive use of erythropoiesis-stimulating agents to raise hemoglobin to a target of 12 g/dL or higher was associated with "serious and life-threatening side-effects and/or death."

The agency ordered a black-box warning for the drugs that recommended the lowest possible dose to slowly raise the hemoglobin concentration to the lowest level that will avoid the need for a blood transfusion.

But as Dr. Thamer and colleagues wrote, "compared with other facility types, we found that large for-profit chains administered higher epoietin doses, used higher dose increases, and had higher achieved hematocrit levels, as well as a larger proportion of patients above the upper limit of hematocrit level."

At the time the study was conducted, the National Kidney Foundation and the FDA were recommending an upper limit of epoietin-induced hematocrit of 36%.

"Among the four largest for-profit dialysis chain facilities, all administered significantly more epoietin than the largest nonprofit chain," Dr. Coyne wrote in his editorial. "The heaviest administrator of epoietin [an unidentified chain] administered 5,845 units per week more epoietin for patients with hematocrit levels of 33% or higher, corresponding to an additional ,000 per year per patient, and an astounding 31,915 U/wk more epoietin for patients with hematocrit levels of less than 33%."

Dr. Coyne noted that nephrologists who refer patients to for-profit centers may not even be aware that their patients are getting such high doses of erythropoiesis-stimulating agents, because multipage standing orders for patients may include clauses that allow dose escalation for anemia.

"Nephrologists often turn over management to anemia managers (dialysis chain employees), who have a vested interest in maintaining hemoglobin level higher than 11 g/dL, not necessarily between 11 and 12 g/dL," Dr. Coyne wrote. "In addition, many nephrologists may have been convinced that it is in the interest of patients to always maintain hemoglobin levels higher than 11 g/dL, and that exceeding a hemoglobin level of 12 g/dL is acceptable (even desirable) based on observational data."

In November 2006, European investigators with the Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE) trial suggested that early complete correction of anemia with a recombinant erythropoietin in patients with chronic kidney disease does not reduce the risk of cardiovascular events.

In fact, aiming for a target hemoglobin of 13.5 g/dL may increase the risk for cardiovascular events compared with a target of 11.3 g/dL, without adding any apparent quality-of-life benefit, according to U.S. and Irish investigators in the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial. Results of the CREATE and CHOIR trials were published in the Nov. 16, 2006, issue of the New England Journal of Medicine.

In their study, Dr. Thamer and colleagues drew on data from the U.S. Renal Data System that were used to identify 159,522 adult Medicare-eligible, end-stage renat disease patients who were receiving in-center hemodialysis during November and December 2004.

They created regression models to estimate mean epoietin doses and dose adjustment by profit/not-for-profit status, chain, and affiliation status (e.g., hospital affiliated or standalone).

The main outcome measure was the weekly mean epoetin dose administered in December, and the adjustment in dose between November and December.

They found that the 106,116 patients treated in large for-profit dialysis chain facilities "were consistently administered the highest doses of epoetin regardless of anemia status."

As noted by Dr. Coyne, for-profit centers, compared with non-profit facilities, administered am average 3,306 U/week of epoetin.

"Among the six large chain facilities with a similar patient case-mix, the average dose of epoetin ranged from 17,832 U/wk at chain 5 (nonprofit facilities with a mean hematocrit level of 34.6%) to 24, 986 U/wk at chain 2 (for-profit facilities with a mean hematocrit level of 36.5%)," the investigators wrote.

They also found that for patients with hematocrit levels less than 30%, for-profit facilities, compared with non-profits, increase epoietin doses on average by nearly a factor of three, and by a factor of three for patients with hematocrit levels from 30% to 33%.

In addition, when patients were in hematocrit range (33% to 36%), non-profits decreased the epoietin dose slightly, while for-profits, on average, bumped it up further.

"Based on the available evidence from clinical trials, maintaining hemoglobin levels between 10.5 and 11.5 g/dL will reduce transfusion requirements in patients with chronic kidney disease who are receiving dialysis," Dr. Coyne wrote.

"This means rarely initiating an erythropoiesis-stimulating agent if hemoglobin level is above 10 g/dL, and changing the erythropoiesis-stimulating agent dose by approximately 25% monthly whenever the hemoglobin level is above or below this range in a patient treated with an erythropoiesis-stimulating agent," he continued. The erythropoiesis-stimulating agent dose should be reduced by approximately 50% or stopped when the hemoglobin level exceeds 12.5 g/dL. This management strategy is good for patients, and would be far less expensive for society."

Dr. Thamer and colleagues acknowledged that their study was limited by a lack of data on factors that might be relevant to epoietin responsiveness such as iron levels and nutritional status or the route of epoietin administration.