Monitoring of Erythropoietin Stimulating Agents for Beneficiaries with End Stage Renal Disease

I applaud a rational process to for managing Hb /anemia in CKD/ESRD patients. Hb/Hct can change sporadically or as part of a trend. To minimize off /on changes in EPO/ESA dose in response to isolated solitary values above or below a given threshold, trends on Hb are needed and dose changes made in response to these.

A three month period should be sufficient to determine a trend since most dialysis snit will obtain 3-6 Hb values in that time period. If the increase in HB > 13 is part of a clear trend over time, then even the first excursion should lead to a change of 20-25% in ESA dose. Certainly by the second such excursion above 13, a dose change should be made. There is no excuse for not making a change and allowing 3 consecutive months with HB > 13 to occur and suggests that the algorithm being used is inadequate/improper or someone has fallen asleep at the wheel. I agree that in the latter event a more draconian reduction in dosage should be mandated on the caretaker.

My experience has been that in some cases, the Hb over 13 will persist in some patients even though monthly decreases of 20-25% are made and it is the 3rd through 5th dose de crease which produces a decrease but than a rapid descent through the target to a Hb below 11 g/dl. I would recommend that in the properly managed patients in whom there has been a clear intent to reduce dose of ESA each month for Hb > 13 in previous months, that in the 3rd month a 50% reduction not be mandated but that the caretaker be allowed to continue to reduce dose but at a slower pace so he does not produce a rapid fall in Hb. What is important is that the dose be reduced at a rate and to an absolute amount that produced a correction to a Hb of 11-12.5 slowly

I also applaud the reduction in total monthly dosage from 500K to 400K. Frankly I favor a limit on the maximum per dialysis dose of 20,000 Units epoetin in a 70 Kg ?standardd? man. Blood volume and red blood cell volume are not weight proportional because fat tissue has a lower capillary density. Thus even in the largest obese individuals, the dose should not exceed 30,000 per treatment which is very close to the ceiling proposed. High dosage invariablu means resistance. The cause for resistance should be searched for rather than blindly escalating ESA dose.

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CMS has recently proposed limiting the amount of Erythropoiesis Stimulating Agent (ESA) administered in the dialysis centers to End Stage Renal Disease (ESRD) patients to 400,000 units of Epogen or 1200 mcg of Aranesp per month. While anemia in large majority of ESRD patients is due to lack of naturally occurring erythropoietin which responds well to moderate doses of ESA, some patients who have anemia complicated by other co-morbid problems may require large doses of ESA.

We reviewed our own usage of ESA in the month of July 2007. The month of July 2007 had 26 possible dialysis days with equal number of dialysis opportunity days for Monday-Wednesday-Friday (MWF) and Tuesday-Thursday-Saturday (TTS) groups. Of the 976 patients who received at least one dose of ESA, 19 (1.9%) received over 400,000 units of Epogen. 14 of the 19 patients were ethnic minorities (5 African Americans, 8 Hispanics and 1 Asian American), ages ranged from 32 to 93, 11 were male. 11 (58%) of the 19 had Hgb levels > 10 gm/dl. Co-morbid conditions were as follows: 5 patients had morbid obesity (BMI > 35); 5 patients had severe secondary hyperparathyroidism despite vitamin D and calcimimetic drugs and patients were either unsuitable for surgery or refused surgery; 4 had cancer; 2 had AIDS and 2 had other blood disorders. 14 patients had received intravenous (IV) iron therapy. Of the 5 patients who did not receive IV iron treatment, 2 had documented allergies to IV iron and were being treated with oral iron supplements, and 3 had substantially elevated ferritin levels. 15 patients were on Medicare, 2 on Medicaid and the remaining 2 had commercial insurance. The average monthly dose of Epogen for all patients at our centers was 80,200 (~6200 units per treatment) units and 112 mcg of Aranesp per month.

Atlantic Dialysis Management Services manages 9 nephrologist-owned dialysis centers in the New York area. We have noticed a 11% reduction in ESA usage in the second quarter of 2007 compared to the first quarter. We attribute this reduction to the Black Box warning issued by the FDA. If we had “capped” the ESA usage at 400,000 units of Epogen per patient, we would have saved $86,000 annually but 11 of the 19 patients may not have had the full benefit of the drug.

I believe that the ceiling proposed by CMS is arbitrary and discriminatory. Our experience indicates that fewer than 2% of ESRD patients receiving ESA need more than 400,000 units of Epogen per month. We have achieved acceptable Hgb levels in nearly 60% of these patients who have not responded to lower doses of ESA. Less than 1% of patients on ESA failed to achieve acceptable Hgb levels despite unrestricted use Epogen above 400,000 units per month and all of these patients had significant, often non-reversible, co-morbid conditions contributing to hyporesponsiveness to ESAs.

CMS policy does not take into consideration that some patients will be dialyzed 14 times in month instead of the usual 13. In those months some additional patients might be pushed above the 400,000 unit per month ceiling.

CMS policy discriminates against ESRD patients who receive their ESA administered to them in the dialysis center only. Such restrictions do not apply in other circumstances such as physician offices and oncology practices. In its recent memo regarding usage of ESA for non-renal disease indications (accessed at https://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?id=203 on 8/15/2007), CMS initially proposed a monthly maximum dosage for ESA. However, upon review of public comments and the FDA label, CMS decided against an arbitrary maximum monthly dosage, noting that the FDA labeled use is for weight based dosing. Many ESRD patients who go above the ceiling have medical diseases as co-morbid problems in addition to ESRD that would have allowed them to receive higher doses, if only they did not have ESRD.

I would like to suggest that CMS either eliminate the maximum dose ceiling entirely, as was done with non-renal diseases, or review these small number of claims above the ceiling manually to justify medical necessity. If our experience can be applied to entire ESRD population, this might involve manual review for approximately 7000 patients in the country.

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CMS has recently proposed limiting the amount of Erythropoiesis Stimulating Agent (ESA) administered in the dialysis centers to End Stage Renal Disease (ESRD) patients to 400,000 units of Epogen or 1200 mcg of Aranesp per month. While anemia in large majority of ESRD patients is due to lack of naturally occurring erythropoietin which responds well to moderate doses of ESA, some patients who have anemia complicated by other co-morbid problems may require large doses of ESA.

We reviewed our own usage of ESA in the month of July 2007. The month of July 2007 had 26 possible dialysis days with equal number of dialysis opportunity days for Monday-Wednesday-Friday (MWF) and Tuesday-Thursday-Saturday (TTS) groups. Of the 976 patients who received at least one dose of ESA, 19 (1.9%) received over 400,000 units of Epogen. 14 of the 19 patients were ethnic minorities (5 African Americans, 8 Hispanics and 1 Asian American), ages ranged from 32 to 93, 11 were male. 11 (58%) of the 19 had Hgb levels > 10 gm/dl. Co-morbid conditions were as follows: 5 patients had morbid obesity (BMI > 35); 5 patients had severe secondary hyperparathyroidism despite vitamin D and calcimimetic drugs and patients were either unsuitable for surgery or refused surgery; 4 had cancer; 2 had AIDS and 2 had other blood disorders. 14 patients had received intravenous (IV) iron therapy. Of the 5 patients who did not receive IV iron treatment, 2 had documented allergies to IV iron and were being treated with oral iron supplements, and 3 had substantially elevated ferritin levels. 15 patients were on Medicare, 2 on Medicaid and the remaining 2 had commercial insurance. The average monthly dose of Epogen for all patients at our centers was 80,200 (~6200 units per treatment) units and 112 mcg of Aranesp per month.

Atlantic Dialysis Management Services manages 9 nephrologist-owned dialysis centers in the New York area. We have noticed a 11% reduction in ESA usage in the second quarter of 2007 compared to the first quarter. We attribute this reduction to the Black Box warning issued by the FDA. If we had “capped” the ESA usage at 400,000 units of Epogen per patient, we would have saved $86,000 annually but 11 of the 19 patients may not have had the full benefit of the drug.

CMS policy does not take into consideration that some patients will be dialyzed 14 times in month instead of the usual 13. In those months some additional patients might be pushed above the 400,000 unit per month ceiling.

CMS policy discriminates against ESRD patients who receive their ESA administered to them in the dialysis center only. Such restrictions do not apply in other circumstances such as physician offices and oncology practices. In its recent memo regarding usage of ESA for non-renal disease indications (accessed at https://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?id=203 on 8/15/2007), CMS initially proposed a monthly maximum dosage for ESA. However, upon review of public comments and the FDA label, CMS decided against an arbitrary maximum monthly dosage, noting that the FDA labeled use is for weight based dosing. Many ESRD patients who go above the ceiling have medical diseases as co-morbid problems in addition to ESRD that would have allowed them to receive higher doses, if only they did not have ESRD.

I would like to suggest that CMS either eliminate the maximum dose ceiling entirely, as was done with non-renal diseases, or review these small number of claims above the ceiling manually to justify medical necessity. If our experience can be applied to entire ESRD population, this might involve manual review for approximately 7000 patients in the country.

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CMS has recently proposed limiting the amount of Erythropoiesis Stimulating Agent (ESA) administered in the dialysis centers to End Stage Renal Disease (ESRD) patients to 400,000 units of Epogen or 1200 mcg of Aranesp per month. While anemia in large majority of ESRD patients is due to lack of naturally occurring erythropoietin which responds well to moderate doses of ESA, some patients who have anemia complicated by other co-morbid problems may require large doses of ESA.

We reviewed our own usage of ESA in the month of July 2007. The month of July 2007 had 26 possible dialysis days with equal number of dialysis opportunity days for Monday-Wednesday-Friday (MWF) and Tuesday-Thursday-Saturday (TTS) groups. Of the 976 patients who received at least one dose of ESA, 19 (1.9%) received over 400,000 units of Epogen. 14 of the 19 patients were ethnic minorities (5 African Americans, 8 Hispanics and 1 Asian American), ages ranged from 32 to 93, 11 were male. 11 (58%) of the 19 had Hgb levels > 10 gm/dl. Co-morbid conditions were as follows: 5 patients had morbid obesity (BMI > 35); 5 patients had severe secondary hyperparathyroidism despite vitamin D and calcimimetic drugs and patients were either unsuitable for surgery or refused surgery; 4 had cancer; 2 had AIDS and 2 had other blood disorders. 14 patients had received intravenous (IV) iron therapy. Of the 5 patients who did not receive IV iron treatment, 2 had documented allergies to IV iron and were being treated with oral iron supplements, and 3 had substantially elevated ferritin levels. 15 patients were on Medicare, 2 on Medicaid and the remaining 2 had commercial insurance. The average monthly dose of Epogen for all patients at our centers was 80,200 (~6200 units per treatment) units and 112 mcg of Aranesp per month.

Atlantic Dialysis Management Services manages 9 nephrologist-owned dialysis centers in the New York area. We have noticed a 11% reduction in ESA usage in the second quarter of 2007 compared to the first quarter. We attribute this reduction to the Black Box warning issued by the FDA. If we had "capped" the ESA usage at 400,000 units of Epogen per patient, we would have saved $86,000 annually but 11 of the 19 patients may not have had the full benefit of the drug.

I believe that the ceiling proposed by CMS is arbitrary and discriminatory. Our experience indicates that fewer than 2% of ESRD patients receiving ESA need more than 400,000 units of Epogen per month. We have achieved acceptable Hgb levels in nearly 60% of these patients who have not responded to lower doses of ESA. Less than 1% of patients on ESA failed to achieve acceptable Hgb levels despite unrestricted use Epogen above 400,000 units per month and all of these patients had significant, often non-reversible, co-morbid conditions contributing to hyporesponsiveness to ESAs.

CMS policy does not take into consideration that some patients will be dialyzed 14 times in month instead of the usual 13. In those months some additional patients might be pushed above the 400,000 unit per month ceiling.

CMS policy discriminates against ESRD patients who receive their ESA administered to them in the dialysis center only. Such restrictions do not apply in other circumstances such as physician offices and oncology practices. In its recent memo regarding usage of ESA for non-renal disease indications (accessed at https://www.cms.hhs.gov/mcd/viewdecisionmemo.asp? id=203 on 8/15/2007), CMS initially proposed a monthly maximum dosage for ESA. However, upon review of public comments and the FDA label, CMS decided against an arbitrary maximum monthly dosage, noting that the FDA labeled use is for weight based dosing. Many ESRD patients who go above the ceiling have medical diseases as co-morbid problems in addition to ESRD that would have allowed them to receive higher doses, if only they did not have ESRD.

I would like to suggest that CMS either eliminate the maximum dose ceiling entirely, as was done with non-renal diseases, or review these small number of claims above the ceiling manually to justify medical necessity. If our experience can be applied to entire ESRD population, this might involve manual review for approximately 7000 patients in the country.

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Please, please, advise on the proper (per CMS, of course) way to handle contingencies that occur in the management of kidney failure anemias, and consider covering the management of contingencies as a routine when policies change or new policies are released. This will make the policy clear to all rather than leaving it to carriers to pull a policy or clarification from their somewhere after the fact.

For examples, what should be done with the ESA dosing if an acute blood loss occurs during the time the hemoglobin has been more that 13 for a) 1-3 months; or b) >3 months? Do we just say give blood transfusions until the review period ends (still costly with, the added risk of blood bourne diseases), or can we do the medically correct action and raise the ESA dose until the hemoglobin recovers into the target range, and receive appropriate reimbursement for the increased dose? Do the doses given in the hospitalized patient count toward the monthly maximum dose, and if so, who is responsible for tracking the dosing (since some hospital stays might be out of the area or the data not available in a timely manner to the outpatient unit)? What to do if a transfusion leads to a hemoglobin >13 (the transfusion meaning the hemoglobin was well below the goal at some point on whatever baseline ESA dose, and when the correct dosing change would be an increase rather than a decrease? I would be glad to map out all of the problems encountered in our day to day dealings with ESA policies if CMS is interested.

Thanks RGC

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I am concerned about the lowering of the ceiling on Aranesp to 1200 units/month & EPO to 400,000 units/month. While few patients require doses above these, those that do are extremely complex and vulnerable. I find these patients at high risk for multiple transfusions, and I am focused on addressing their medical as well as quality of life issues. I work to coordinate care closely with other specialties to focus on the individual patient. Arbitrary ceilings limit my ability to individualize care and to practice good medicine for the individual patient. I believe the ceilings should be removed, or a process for medical justification for exceptions should be put in place.

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August 17, 2007

Dr. Steve Phurrough
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
Department of Health and Human Services
7500 Security Boulevard
Mail Stop C1-0906
Baltimore, MD 21244

Re: Proposed Coverage Policy on “Monitoring ofErythropoietin Stimulating Agents forBeneficiaries with End Stage Renal Disease

Dear Dr. Phurrough,

As America’s largest dialysis patient organization, DaVita Patient Citizens (DPC) is proud to represent over 20,000 pre-dialysis and dialysis patients and their families. On a wide variety of issues, we seek to ensure that the patients’ point of view is heard and considered by policy makers so that continued progress may be made in the quality of care and life for patients with kidney disease. DPC is pleased to have the opportunity to provide comment on the Centers for Medicare and Medicaid Services’ (CMS) changes to its policy entitled “Monitoring of Erythropoietin Stimulating Agents for Beneficiaries with End Stage Renal Disease.”

50% Reduction of Erythropoietin

On July 20, 2007, CMS announced that they would again modify their erythropoiesis stimulating agent (ESA) Monitoring Policy (EMP). According to CMS’ own release, “CMS is adding a provision that will reduce by 50 percent the reported ESA dosage used by the dialysis facility for which payment will be made if the facility reports that the beneficiary’s hemoglobin has exceeded 13 g/dL for three consecutive billing cycles” DPC is concerned that CMS’ proposed policy will adversely affect those individuals the policy is designed to protect, the dialysis patients.

As you are aware, anemia is a serious, life-threatening problem affecting almost all dialysis patients. It causes us fatigue, weakness and increased risk of hospitalization and death. With the introduction and appropriate dosing of ESAs, we no longer require blood transfusions, we require less medical attention and hospitalization, and we are better able to lead productive, quality lives. We applaud CMS for working with patients and the kidney care community to create an EMP that is beneficial to both CMS and the community. However payment structures can often adversely impact patient care. DPC feels there should not be any barriers to patients like us receiving the treatments and medications as prescribed by our doctors.

DPC recognizes CMS’ commitment to “promote efficient and appropriate use of medical interventions, protect beneficiaries, and enable providers to furnish high quality care.” However, we also recognize that each dialysis patient is unique—with different ethnic/racial backgrounds and co-morbidities. Similarly, each dialysis patient reacts different to the administration of EPOGEN® and thus EPOGEN® reductions. As a result, DPC is concerned with a policy that would reduce by 50% the amount of EPOGEN® administered in the second month (third billing cycle) if the hematocrit level exceeds 39. A two month period to return a patient is to the targeted hematocrit level is not adequate and does not provide for the nephrologist to treat the patient as he/she feels fits. Since each patient will respond differently to reductions in EPOGEN®, we feel that nephrologist should have the flexibility to gradually reduce amount of EPOGEN® administered and to return the patient back to the targeted level.

Reduction of Medically Unbelievable rate to 400,000

CMS has similarly announced a reduction in the medically unbelievable threshold from 500,000 to 400,000 IU’s per month. As stated previously, all dialysis patients are different. DPC is concerned that reducing the threshold to 400,000 IU’s per month could disproportionately impact minority patients and further exacerbate the patients’ anemia. The current 500,000 IU’s per month allows nephrologists to continue to treat those most anemic patients as they feel is necessary. DPC would like CMS to maintain the existing dosage ceiling of 500,000 IU’s. If CMS finalizes the policy at 400,000 IU’s per month, we are requesting that you include a means for appeal for those patients that do require higher dosages.

DPC is committed to working with CMS to produce the best policy that allows for the stewardship of limited financial resources and also allow nephrologists to continue to treat their patients as they feel fit. The decisions made by CMS directly affect us and our membership on a daily basis. DPC would like to offer to be a resource to CMS as it continues to evaluate changes to the EMP. However, we would prefer that patients have an opportunity to provide their voice and opinions before policies are finalized. Please feel free to contact DPC if we can be of further assistance.

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It is right and optimal that CMS NOT force a stop of ESA therapies when a kidney patient''s hemoglobin rises above 12.0.

It is very difficult to maintain a target Hemoglobin 11-12 with precise EPO titrations without occasionally having Hemoglobin rise above 12.0. Stopping EPO at that point in time is contrary to proper pharmacologic use of a therapeutic hormone. Consider the metabolic chaos we would witness were we to act in that manner with thyroid hormone replacement - stopping thyroid hormone when the measured T4 is at target or slightly above - the proper intervention is to reduce the hormone replacement dose.

Then, we often will have a patient with Hemoglobin above 13 and we will titrate the EPO dose downward appropriately. However, an occasional patient will exhibit an abrupt drop in his/her Hemoglobin level to values less than 11 within 4-6 weeks. Our measured response is to raise the EPO dose.

The formula proposed would probably penalize this action, as it is likely that the total monthly dose would exceed a prior month''s dose. This requires a policy adjustment to accomodate the usual and customary - and now standard of care dose titrations for ESA as a patient''s hemoglobin value DECLINES. The policy, as written, appears to address and be concerned about ESA dose titrations as a patient''s hemoglobin is INCREASING. ESA dose titrations as a patient''s hemoglobin declines are commonly and customarily an increase in dose. The goal is to maintain a patient''s hemoglobin above 11.

Please recall the intense AAKP and NKF lobby and appeal in 1996 and 1997 - led by patients - to permit Epo dosing that would maintain Hgb in the 11-12.5 range. This was their cry for consideration of their health maintenance and reasonable quality of life - which dips in synchrony with Hemoglobin declines.

Thank you.

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I object to limiting the reimbursable Aranesp dose to 1200mcg per month. I have a number of patients who require more than this in order to manage their anemia to the target hemoglobin levels (obese patients in particular). The statement that doses higher than 1200 mcg per month are "typographical errors" is patently false with respect to my practice. This decision also creates an incentive to manage anemia with blood transfusions which 1) is riskier for patients and 2) takes us back to the days of dialysis before the advent of ESA's, and 3) is also expensive

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I am concerned that this policy will not address the needs of some patients who require higher doses of ESA's to achieve a target hemoglobin between 11 and 12. With the decrease in the maximum allowed monthly dosing, an opportunity to appeal should be allowed in order to ensure that those patients who require higher dosing are able to receive it without a penalty of reduced payment to the facility. Allowing the FI's to conduct a medical review of such claims, and paying the claims when appropriate, would be the fair and just approach.

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While it is essential to refine and revise the monitoring of ESA in ESRD it is the small part of a major problem related to the effects of the influence of the pharmaceutical industry on the clinician and clinical practice. UNBIASED education to meet the goals set and accepted must be accomplished. Additionally, wherever possible IV iron supplementation must be maintained at adequate levels to ensure the smallest dose of ESA necessary for healthy red blood cells and appropriate Hemoglobin levels.

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