Erythopoiesis Stimulating Agents (ESA) in Anemia Related to Kidney Disease

CMS has called this meeting of the panel to review the available evidence on the use of erythropoiesis stimulating agents (ESAs) to manage anemia in patients who have chronic kidney disease (CKD). Medicare currently does not have a national coverage determination for the use of ESAs for anemia in patients who have CKD. ESAs are synthetic analogs of the hormone erythropoietin.

Anemia is prevalent in patients with kidney disease and is more common as CKD progressively worsens. Recombinant genetic technologies are used to produce the ESAs that are commonly used to treat anemia in CKD patients. ESAs raise hemoglobin and hematocrit levels in anemic patients who have CKD, including both those on dialysis and those who do not require dialysis.

ESAs were introduced in 1989 and initially administered usually only to patients at risk for blood transfusions. During the subsequent 20 years, ESA use increased, resulting in the common practice of administering ESAs to CKD patients who have anemia, but not necessarily only to those who are at risk for transfusion. Currently, over 95% of end stage renal disease (ESRD) patients receive ESAs. It is unclear how many pre-ESRD CKD patients receive ESAs for anemia.

In the fall of 2006 through winter 2007, a succession of published reports highlighted the dangers, including increased mortality, associated with the use of ESAs. These were in addition to other danger signals seen since the introductions of ESAs in 1989. These findings, based on the results of clinical trials, were followed by a series of changes including boxed warnings in the FDA approved labeling for ESAs and a “Dear Doctor Letter” regarding concerns about the safety of ESAs.

February 19, 2010

March 18, 2010

March 25, 2010

April 13, 2010

August 3, 2010

Clifford Goodman, PhD, Chair
Saty Satya-Murti, MD, Vice Chair
Louis Jacques, MD, Director, Coverage and Analysis Group
Maria Ellis, Executive Secretary

7:30 - 8:00 AM  

8:00 - 8:15 AM

8:15 - 8:40 AM  

8:40 - 9:05 AM  

9:05 - 9:15 AM  

9:15 - 10:00 AM

10:00 - 10:15 AM  

10:15 - 11:25 AM

Public attendees, who have contacted the executive secretary prior to the meeting, will address the panel and present information relevant to the agenda. Speakers are asked to state whether or not they have any financial involvement with manufacturers of any products being discussed or with their competitors and who funded their travel to this meeting.

11:25 - 11:35 AM

Public Attendees who wish to address the panel will be given that opportunity

11:35 - 12:00 PM

12:00 - 1:00 PM  

1:00 - 2:00 PM    

2:00 - 3:00 PM

The Chairperson will ask each panel member to state his or her position on the voting questions

3:00 - 4:00 PM   

4:00 - 4:30 PM     

Download Meeting Minutes [PDF, 139KB].

1. How confident are you that there is sufficient evidence to determine whether using a medical intervention (e.g., blood transfusion, iron therapy, or ESAs) to maintain or raise the hemoglobin or hematocrit levels of anemic CKD patients affects each of the health outcomes below?
   1. Exercise (activity) tolerance
   2. Vascular events (stroke, myocardial infarction, congestive heart failure)
   3. Patient perceived quality of life
   4. Survival

2. For any health outcome listed in Question 1 for which the panel indicates at least intermediate confidence (mean score ≥ 2.5) in the sufficiency of evidence, how confident are you that maintaining or raising hemoglobin or hematocrit levels of anemic CKD patients improves each such health outcome?

3. a. For any health outcome addressed in Question 2 for which the panel indicates at least intermediate confidence (mean score ≥ 2.5), how confident are you that there is sufficient evidence to determine whether the use of ESAs to maintain or raise hemoglobin or hematocrit levels of CKD patients improves each such health outcome?

2. For any health outcome addressed in Question 3.a. for which the panel indicates at least intermediate confidence (mean score ≥ 2.5), how confident are you that the use of ESAs to maintain or raise hemoglobin or hematocrit levels of CKD patients improves each such health outcome?

4. a. How confident are you that there is sufficient evidence to determine whether the use of ESAs to maintain or raise the hemoglobin or hematocrit levels of anemic CKD patients worsens any health outcome listed in Question 1?

2. For any health outcome addressed in Question 4.a. for which the panel indicates at least intermediate confidence (mean score ≥ 2.5), how confident are you that the use of ESAs to maintain or raise hemoglobin or hematocrit levels of CKD patients worsens each such health outcome?

5. Please discuss any impact of the following factors on the conclusions reached above.
   1. Whether the CKD patient is undergoing chronic dialysis or is in pre-dialysis status.

   2. Whether the CKD patient has pretreatment baseline hemoglobin levels:
      1. < 7 g/dL
      2. ≥7g/dL to < 9 g/dL
      3. ≥9 g/dL to <12g/dL
      4. ≥ 12 g/dL

   3. Whether an appropriate target hemoglobin or hematocrit has been set for the CKD patient

   4. Whether the ESA dosing strategy has been implemented to minimize the rapidity of hemoglobin or hematocrit rise and/or oscillations in their levels

   5. Whether the CKD patient has demonstrated a blunted or “non-response” to interventions to raise hemoglobin or hematocrit

   6. Whether the CKD patient has been evaluated to determine the etiology (cause) of the anemia

   7. Whether the CKD patient demonstrates cardiac, cerebral or other vascular comorbidities

   8. Other

6. What clinical trials designs would be most desirable to fill in any identified evidence gaps?

Download scoresheet [PDF, 94KB]