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Letter from ANNA to the Centers for Medicare and Medicaid Services regarding proposed policy for monitoring of Erythropoietin for Beneficiaries with End Stage Renal Disease.

October 6, 2004

Sean R. Tunis, MD, MSc

Director, OCSQ

Chief Medical Officer

Centers for Medicare & Medicaid Services

7500 Security Boulevard, S3-02-01

Baltimore, MD 21244-1850

Dear Dr. Tunis,

The American Nephrology Nurses’ Association (ANNA) is a professional nursing organization representing 11,000 nurses nationwide who are involved in the care of individuals suffering from chronic kidney disease. As such, ANNA is the largest organization of nephrology professionals in the country. The vast majority of our members practice in outpatient dialysis facilities. ANNA is also a member of the Kidney Care Partners (KCP) and this letter should be considered as an addition to their comments in response to this draft policy, not in conflict.

ANNA is committed to the provision of high quality care to people with chronic kidney disease (CKD), including CKD Stage 5 on dialysis or end stage renal disease (ESRD). In responding to policy changes such as those specified in the current Centers for Medicare & Medicaid Services (CMS) draft policy for monitoring of erythropoietin (EPO) for beneficiaries with ESRD, we are reminded of the highest priority that guides everyone involved in healthcare: First, do no harm. We are certain that CMS does not intend to implement a policy that would diminish clinical outcomes from their current level. If a revised policy does not support improvement, it should, at a minimum, maintain quality at current levels. With this in mind, we offer the following comments and recommendations.

ANNA is most pleased that this draft policy acknowledges:

  • Patients with hemoglobin levels within the recommended target range have better outcomes than those below the target level.
  • There is considerable natural variability in individual patient hemoglobin levels making it difficult to consistently maintain hemoglobin within a narrow range.
  • Stopping and starting EPO therapy can lead to dramatic dips in hemoglobin levels that may require high doses of EPO to regain the target level again.

Nephrology nurses know that anemia management requires vigilant and continuous monitoring of hemoglobin, iron indices, as well as EPO and iron administration. Nephrology nurses collaborate with physicians to design and carry out anemia therapy protocols. These protocols are designed to provide consistent ongoing management and to help reduce variation in practice. Nephrology nurses are identified to serve as anemia nurse managers in most dialysis facilities across the country. The purpose of this role is to assure appropriate patient assessment, initiate EPO and iron therapy, and to provide the continuous evaluation of patient response to that therapy. Nephrology nurses play a critical role in ongoing quality improvement programs specific to the achievement and maintenance of patients in the desired hemoglobin range as specified by the K/DOQI clinical practice guidelines for anemia in chronic kidney disease.

Anemia management, however, is a complex clinical challenge. Patient responses to this therapy do not necessarily fit into the mold required of a protocol. As patients become malnourished, are hospitalized, develop hyperparathyroidism, lapse into depression, develop an infection, or experience a failed vascular access, the desired hemoglobin level becomes less attainable, requiring an increase in management intensity. This intensity may require several EPO dose changes and additional iron support. Hemoglobins will fluctuate beyond the normal variability seen in more “stable” patients.

Added to this complexity, is the frustration experienced by nephrology nurses who find that considerable time is being spent not necessarily managing a patient to the best clinical outcome, but to a reimbursement policy. While ANNA agrees that we must be fiscally responsible and good stewards of the public trust, and recognizing that the draft policy was most likely intended to ensure appropriate payment for the drug, in fact the policy significantly influences the clinical practice of anemia management.

The draft policy states,

Claims with hemoglobin levels between 13.0 and 13.9 g/dL should be reviewed if the patient has received a monthly dose of EPO greater than 40,000 IU. And,

Claims with hemoglobin levels 14.0 g/dL or greater should be reviewed if the patient has received a monthly dose of EPO greater than 20,000 IU.

Dose limitations. While ANNA’s focus is on the achievement of high quality clinical outcomes, CMS is specifically concerned about the utilization of EPO and its subsequent payment. What is not clear is the rationale to support the actual dose levels stated in the draft policy. Evidence exists to support the individualization of the EPO dose.

  1. The U. S. Food and Drug Administration (FDA) approved package insert for Epogen® states, “The maintenance dose must be individualized for each patient on dialysis. In the U.S. phase 3 multicenter clinical trial in patients on hemodialysis, the median maintenance dose was 75 u/kg TIW, with a range from 12.5 to 525 u/kg.”
  2. National Kidney Foundation (NKF) K/DOQI anemia clinical practice guidelines describe the wide variability in dose response to Epoetin. “An individual patient may respond to as little as 75 u/kg per week.” But the guidelines also point out that 96% of patients will respond to Epoetin at 450 u/kg per week within 4 – 6 months provided that there are adequate iron stores.
  3. In the CMS issued 2003 Annual Report ESRD Clinical Performance Measures the mean weekly Epo dose was 263.7 u/kg with a standard deviation of + 235.2 u/kg. In that report, Figure 38 demonstrates that the mean EPO dose for patients with hemoglobin 12 – 12.9 g/dL is approximately 215 u/kg/week. It also indicates that there is little difference in this mean dose for those patients with hemoglobin 13 – 13.9 g/dL.

Clearly, the dose ceilings put forth by this draft policy will force physicians and nurses to decrease current EPO doses well below therapeutic levels. This can be predicted to lower hemoglobin levels. As is well described in the scientific literature, when the hemoglobin falls, the patient will experience a diminished quality of life and their hospitalization frequency and length of stay will increase. ANNA will not support a policy that results in a diminished therapeutic benefit.

Hemoglobin monitoring. Recognizing that a review of hemoglobin levels is critical to policy implementation, we support efforts that are based on evidence; specifically, a monitoring process that provides an adequate review of actual practice. It is our understanding that the current claims form does not have the capability to provide a comprehensive picture of anemia management. Thus reimbursement decisions are made based on a single point in time hemoglobin and a monthly EPO dose. In fact, this offers an extremely limited perspective and does not support the use of well-tested anemia management practices. Evidence supporting the monitoring and evaluation of dose response exists.

  1. NKF K/DOQI anemia clinical practice guidelines support hemoglobin monitoring every 2 to 4 weeks (maintenance phase). The guidelines very clearly state, “The dose response range is wide, however. Weekly testing of Hgb is recommended following initiation and/or an Epogen dose adjustment to detect changes in Hgb. Less frequent testing could miss the very rapid erythropoietic response or the poor response and prevent an earlier dose adjustment.”
  2. The FDA approved package insert for Epogen states, “ Because of the length of time required for erythropoiesis – several days for erythroid progenitors to mature and be released into the circulation – a clinically significant increase is usually not observed in less than 2 weeks and may require up to six weeks in some patients.”
  3. Again, the FDA approved Epogen package insert states, “Dose adjustment should not be made more frequently than once a month, unless clinically indicated (emphasis added). After any dose adjustment, the hematocrit should be determined twice weekly for at least 2 to 6 weeks.”
  4. Lacson, etal point out in their 2003 AJKD article (41(1), 111- 124) that hemoglobin varies from one time period to another. The analysis of a large patient population demonstrated that patient movement in and out of hemoglobin categories is extremely frequent.

It is clear that the draft policy permits or withholds reimbursement based on only one point in time hemoglobin when in fact, there may be others during the month used by physicians and nurses to make dose adjustments. The policy must allow for dose titration and adequate time for a thorough evaluation of the patient’s dose response.

In summary, ANNA is unable to support a policy that reduces the therapeutic benefit and leaves patients with diminished health outcomes. As nephrology nurses work to implement evidence-based practices specific to anemia management, we would support a policy that reflects the complexity of anemia and its treatment with Epoetin; i.e., recognition of appropriate dose adjustments related specifically to the hemoglobin level. We would be pleased to work with CMS on a policy that supports the intense monitoring and dose titration required to assure patient achievement and maintenance of clinical outcomes within the desired hemoglobin range.

Additionally, we would like to reiterate our serious concern with Section 207.5 of the Medicare Renal Dialysis Facility Manual. This section restricts reimbursement of EPO therapy for new dialysis patients who do not have a history of prior EPO use until their hemoglobin level falls below 10 g/dL. Our members see incident dialysis patients with hemoglobin levels below 10 g/dL, as well as many others who present with hemoglobin levels between 10 and 11 g/dL without a history of EPO therapy. Current policy requires nurses and physicians to wait until the patient’s hemoglobin level falls below 10 g/dL before EPO can be initiated, knowing full well the associated risks to the patient. In our letter to your office (dated January 13, 2004), ANNA requested your attention to this policy as it presents a significant health risk to those patients initiating dialysis.

ANNA appreciates your review of our concerns and is willing to work with CMS to develop a policy(s) that will support evidence-based anemia management for patients with ESRD.

Sincerely,

Lesley Dinwiddie, MSN, RN, FNP, CNN

President

American Nephrology Nurses’ Association