October 6, 2004 Sean Tunis, M.D., M.Sc. Chief Medical Officer Director, Office of Clinical Standards and Quality Coverage and Analysis Group ATTN: EPO Public Comments, S3-02-01 Centers for Medicare and Medicaid Services 7500 Security Boulevard Baltimore, Maryland 21244-1850 Re: EPO Public Comments, S3-02-01 Dear Dr. Tunis: Kidney Care Partners (KCP) is pleased to have the opportunity to provide the Centers for Medicare and Medicaid Services (CMS) with comments about the Draft Policy for the Monitoring of Erythropoietin for Beneficiaries with End Stage Renal Disease (Draft Policy). KCP is an alliance of members of the kidney care community that works with renal patient advocates, dialysis care professionals, providers, and suppliers to improve the quality of care of individuals with irreversible kidney failure, known as End Stage Renal Disease (ESRD). The goal of the Draft Policy appears to be based more on cost than on care. We believe this is inappropriate and not in the best interest of Medicare beneficiaries. Although KCP members understand that CMS is concerned about the cost of EPO to the Medicare program, we question the appropriateness of controlling cost through restricting patient access by limiting their doses to a drug that has such a positive impact on patients’ quality of life and health status. EPO used in the ESRD context is the only drug singled out for specific monitoring. Its use in oncology is left to the professional judgment of physicians, as is the use of almost all other drugs. The Draft Policy treats ESRD patients unfairly because patients with diseases other than ESRD do not have their drug doses controlled by CMS, but instead can rely upon the judgment of their physicians to provide them with the appropriate doses. Rather than focus on claims review and limitations on payment for patients who are experiencing positive clinical outcomes, we encourage CMS to shift its attention to addressing the problems of patients with hemoglobin levels less than 12.0 g/dL. These patients are often hospitalized more frequently and have additional complications related to their anemia. Improving the quality of care these patients receive and finding ways to increase their hemoglobin could result in dramatic savings to the Medicare program by decreasing their hospital stays and decreasing or eliminating the other health problems they experience due to low hemoglobin levels. One way CMS could accomplish this goal is to permit providers and physicians to initiate EPO therapy when patients’ hemoglobin levels are less than 12.0 g/dL. If patients receive EPO before they reach such devastatingly low hemoglobin levels, their overall health improves and less EPO is required to raise the hemoglobin levels into the desired range. Medicare should focus on obtaining the best possible treatments for all its beneficiaries. Shifting attention to this serious problem would bring agency policy in line with statements from the Congress that called for ensuring that all patients have hemoglobin levels within the K/DOQI range. To summarize, KCP is concerned that: The Immediate Implementation of the Draft Policy Would Be Precipitous and Inappropriately Hasty; The Proposed Dose Thresholds Do Not Account for the Medical Complexities Involved in Administering and Monitoring EPO; The Draft Policy Establishes the Wrong Monitoring Point in Treatment; and As Proposed, the Draft Policy Is Administratively Burdensome. In Section VI, we suggest a solution to these problems as well as an interim measure that would allow for immediate implementation if the steps necessary for the more appropriate solution cannot be accomplished in the short-term. I. Erythropoietin (EPO) Improves Patient Care and Quality of Life Before discussing the Draft Policy, KCP believes it is important to stress why the issue of EPO dosing is so critical to the renal community, and most especially to patients. No treatment has revolutionized care for ESRD patients to the same degree that EPO has. It is truly a miracle drug. Because of the deficiency of erythropoietin production by their diseased kidneys, ESRD patients suffer from severe chronic anemia, which impedes their rehabilitation and significantly affects their quality of life. Before EPO, patients received frequent blood transfusions. Since the introduction of EPO in 1989, the need for these transfusions has been virtually eliminated, saving hundreds of thousands of units of blood each year, reducing the exposure of ESRD patients to blood-borne diseases, and avoiding transfusion-induced antibodies that prevent successful transplants. Most importantly, quality-of-life studies document that no other treatment intervention (except for transplantation) enhances patients’ quality of life to the same degree as EPO. Patients report significant increases in energy and activity levels, as well as in their overall health status. Several studies have also indicated that higher hemoglobin levels decrease both hospitalizations and deaths in this patient population. Simply put, EPO improves patients’ quality of care and their quality of life. Any policy that impacts EPO dosing cannot ignore the importance of this drug to patients. A misstep in policy could have a dramatic negative effect on the more than 300,000 Americans with kidney failure. II. The Immediate Implementation of the Draft Policy Would Be Precipitous and Inappropriately Hasty As a threshold matter, we strongly urge CMS to delay implementation of the Draft Policy. This is the appropriate course of action for several reasons. First, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) establishes a new reimbursement policy for all separately billed ESRD drugs, including EPO. These changes are likely to affect the reimbursement of EPO. Given that a major purpose of the Draft Policy is to rein in the cost of EPO to Medicare, it simply does not make sense to implement a new monitoring policy when the amount Medicare pays for EPO is changing. Second, the National Kidney Foundation is revising the K/DOQI Guidelines, which will result in new clinical practice guidelines for administering the drug. Thus, before considering and implementing a new EPO monitoring policy, CMS should review the results of the MMA implementation, as well as the revised K/DOQI Guidelines on Anemia of Chronic Kidney Disease. III. The Proposed Dose Thresholds Do Not Account for the Medical Complexities Involved in Administering and Monitoring EPO Although KCP members appreciate CMS’s efforts to simplify the monitoring policy and the decision to propose a higher hemoglobin/hematocrit level for triggering review, the proposed dose thresholds of 40,000 IU for hemoglobin levels between 13.0 g/dL and 13.9 g/dL and 20,000 IU for hemoglobin levels equal or greater than 14.0 g/dL would disrupt patient care dramatically. A. An Absolute Dosing Policy Would Harm Patients and Contradicts Accepted Practice Guidelines The administration and monitoring of EPO is an extremely complex process because of the substantial intra-patient variability in hemoglobin levels. The dose-response range among all patients is wide. Patients’ comorbidities also significantly affect the dose-response. As the Kidney Epidemiology and Cost Center at the University of Michigan recently reported, current data from the United States Renal Data System (USRDS) indicates that patients with the most severe comorbidities require more EPO to achieve their target hemoglobin levels. These variations mean that providing appropriate care to patients so they reach the K/DOQI target hemoglobin levels may result in some individual measurements that exceed 13.0 g/dL. An absolute dosing policy threatens patient care by placing them on an EPO dose and hemoglobin roller coaster. The Draft Policy’s focus on absolute dosing creates strong incentives for providers to discontinue the administration of EPO abruptly so patients’ hemoglobin levels remain within the dose thresholds. Such a sudden reduction in EPO therapy will lead to steep reductions in patient hemoglobin levels, which could fall below the recommended target ranges. As CMS has recognized, lower hemoglobin levels decrease patients’ overall health status, as well as their energy and activity levels, and is an indication of suboptimal care. An absolute dosing policy also contradicts practice guidelines. The K/DOQI Guidelines recommend that providers should treat increases in hemoglobin levels above the target range by reducing the weekly dose of EPO by 25 percent. This titrating downward approach is also consistent with the Food and Drug Administration (FDA)-approved package indication for EPOGEN that calls for a gradual reduction of the dose. These guidelines focus on gradually reducing doses because rapid reductions compromise patient care. Given the difficulty of predicting the dose-response and of sustaining stable hemoglobin levels, it is inappropriate to implement a monitoring policy that focuses on absolute doses rather than dose adjustments. B. The Proposed Threshold Levels Do Not Correspond with Current Clinical Data KCP members are also concerned that the dosing levels stated in the Draft Policy do not reflect the actual dosing levels associated with current medical data. The Draft Policy calls for a claim review if a patient’s hemoglobin level is between 13.0 g/dL and 13.9 g/dL and he/she received a monthly dose of EPO greater than 40,000 IU or if the level is equal to or greater than 14.0 g/dL and he/she received a monthly dose of EPO greater than 20,000 IU. Based upon surveys conducted by KCP members using their own data, the mean dose for these patients is actually 76,000 IU and 77,000 IU, respectively. The 2003 Annual Report of the ESRD Clinical Performance Measures (CPM) Project found similar dosing levels. These figures are very different from those in the Draft Policy, yet CMS offers no scientific data or explanation as to why the 40,000 IU and 20,000 IU numbers are more appropriate than current practice. KCP strongly urges CMS to review these levels and increase them to make them more consistent with current clinical data. IV. The Draft Policy Establishes the Wrong Monitoring Point in Treatment Another serious flaw with the Draft Policy is that it relies upon the wrong point in treatment for measuring patient’s hemoglobin levels. Under the Draft Policy, Fiscal Intermediaries (FIs) would monitor hemoglobin levels by relying on a single claim form with the last hemoglobin measurement of the claim period and the total monthly EPO dose consistent with current regulatory reporting requirements. EPO doses for individual patients fluctuate throughout a month because each patient’s dose-response differs and may change over time. For example, a patient may have a hemoglobin level within the target range for most of the month, but have a measure at the end of the month that is greater than 13.0 g/dL. The higher levels at the end of the month may be the result of a physician-prescribed dosing change to maintain the target. In some cases, a patient may end the month with higher levels absent any dosing changes. It is critical for the agency to recognize that EPO dose adjustments are made in response to the previous hemoglobin measure, not in anticipation of future levels. The fluctuation in hemoglobin levels is due primarily to intra-patient hemoglobin variability. A methodology based on the last measure and previous EPO doses provides the wrong snapshot of a patient’s status. CMS should modify the policy to ensure that the hemoglobin evaluation is based on comparison measures during consecutive months rather than solely based on the last measure of the claim period. As described below, this could be accomplished with a small change to the claims form. In that way, providers and physicians can modify EPO doses appropriately. V. As Proposed, the Draft Policy Is Administratively Burdensome If implemented, the Draft Policy would divert resources from patient care to deal with the administrative burdens associated with the policy itself. First, it would result in a high number of false high hemoglobin claims that would divert limited resources to the review process. Second, dialysis facilities will have a difficult time implementing the policy because it fails to recognize that the dialysis facilities that are bound by the policy do not control the EPO prescribing patterns of physicians. The use of absolute dosing measures in the Draft Policy would mean that more claims trigger review than ever before. As mentioned previously, a large proportion of ESRD patients who have a hemoglobin level of less than 13.0 g/dL during most of the month on a stable dose may have a high hemoglobin level at the end of the month because of their physiological response to the drug and intra-patient variability. The hemoglobin measure reported on the claims form comes from the last measurement of the month. This means that the FIs would have to evaluate whether a claim should be reviewed based on these anomalous measurements. Although the review process would lead to the appropriate conclusion (namely, that the claims are appropriate), a great deal of time, effort, and money would have to be expended to reach this conclusion. The same conclusion could be reached without the expenditure of valuable resources if a different methodology were in place. In addition to draining resources from a sector of the health care industry that is already making do with less, fear of these false high hemoglobin claims will deter providers from administering the prescribed, medically necessary level of EPO to their patients. Because providers will not want to be subject to numerous claims reviews, they may try to keep patients’ hemoglobin levels lower, as was the case when CMS implemented a previous EPO policy in the mid-1990s. The number of patients with hemoglobin levels greater than 10.3 g/dL fell during the time CMS enforced the policy. Lower hemoglobin levels reduce a patient’s overall health status, which is not desirable. The incentive to underutilize EPO also places dialysis facilities in a legal conundrum. Physicians, not facilities, write the prescriptions that determine each patient’s EPO doses. Facilities may not change these prescribed doses without risking being accused of “practicing medicine,” which they are forbidden to do under state laws. Facilities should not be placed in the position of second guessing physicians and interfering with their best medical judgment. Doing so would also violate the prohibition of federal interference with the practice of medicine. If the facility provides the prescribed dose and that dose is outside of the CMS policy, the facility risks not receiving payment for the drug. Unless a beneficiary has signed an Advance Beneficiary Notice (something most have not done), the facility may be viewed as providing free care, which would violate federal and state fraud and abuse laws. This is a Catch-22 situation in which the facilities find themselves always the losers. Finally, if CMS maintains its current withholding practice, a high number of false high hemoglobin claims will destabilize the industry. CMS’s current practice is to withhold reimbursement pending review of a claim. With the high number of claims likely to be subject to review under the draft policy, facilities are likely to encounter serious financial hardship while treatment reimbursement is also withheld as the EPO-portion of the claims are reviewed. Therefore, reviews should occur post-payment only. VI. Recommended Policy Revisions To resolve the problems noted above, KCP suggests that CMS delay implementation of the Draft Policy. Alternatively, we suggest that CMS modify the Draft Policy so that review is triggered only when an appropriate downward titration does not occur or medical justification is not presented. CMS could accomplish this by modifying the claims form to establish a two-month review process. If CMS were to delay the implementation of the Draft Policy, in the interim CMS should ensure the stability of payments in the ESRD program by reissuing the current monitoring policy. Although KCP members do not believe the current policy uses either the correct hemoglobin/hematocrit level for triggering review or dose thresholds, we recognize the need to have a nationwide policy in place to ensure that providers are not subject to countless reviews because of confusion on the part of FIs. By far the most appropriate approach would be to establish a two-month rolling review of patients’ hemoglobin levels and their EPO dosing. CMS could modify the claims form, which it is already in the process of doing for the case-mix adjustment, so it contains clinical data regarding these two measures from two consecutive months. With this information, CMS could compare the current and previous months’ data. The comparison would allow CMS to establish the following review protocol: No Review: If the prior month hemoglobin value was 13.0 g/dL or greater at any dose level and the current month’s hemoglobin level remains at 13.0 g/dL or greater, but the dose is reduced by the appropriate amount, there should be no review because the provider is appropriately reducing the patient’s dose in accordance with the Epogen package insert and the K/DOQI Guidelines. No Review: If the prior month value was less than 13.0 g/dL at any dose level and the current month’s level is 13.0 g/dL or above or less than 13.0 g/dL (at any dose) there should be no review because although the hemoglobin level is above the target range, the provider has not had sufficient time to gradually decrease the dose to respond to the increase in the hemoglobin level. Review: If the prior month value was 13.0 g/dL or greater and the patient received 100,000 units or more and the current month’s level is 13.0 g/dL or above and there has been no reduction in the EPO dose, there should be a review to determine whether it is medically appropriate. In absence of a reduced dose, the reimbursement rate should be cut by the appropriate percentage to correspond to what would have been the appropriate reduction rather than to set the rate at an arbitrarily low level that does not correspond with clinical data. Alternatively if CMS concludes that modification to the claims form or use of a modifier is not feasible, CMS could trigger a review of claims when a patient’s hemoglobin is 13.0 g/dL or greater and the monthly total of EPO doses exceeds the mean dose plus one standard deviation (or approximately 100,000 units) for all U.S. facilities for the prior twelve months. Based upon the survey of their own data, KCP members suggest that for the first year the mean dose would be 77,000 IU (plus one standard deviation). Given that this approach would require revising the dosing level on an annual basis, we strongly urge CMS to use this only as a temporary measure until it can adopt a two-month comparison methodology. Any review, including reviews under this alternative approach, should be conducted post-payment to ensure the stability of the industry. VII. Conclusion KCP members sincerely appreciate your review of our concerns and look forward to working with the agency on this issue. Please do not hesitate to contact Kathy Means at 202-457-6328 if you have questions regarding these comments. Sincerely, Kathleen E. Means President Kidney Care Partners Attachments  A list of Kidney Care Partners coalition members is included in Attachment A. Joseph W. Eschbach, et al., “Recombinant Human Erythropoietin in Anemic Patients with End-Stage Renal Disease,” 111 Annals of Internal Medicine 992 (1989). National Kidney Foundation (NKF), K/DOQI Guidelines, Guideline 15. Id., Guideline 16. These values represent dosage of less than 85 units/Kg, which is well within reasonable dosing schedules. In addition, these mean values have correspondingly large standard deviation. CMS, 2003 Annual Report ESRD Clinical Performance Measures Project, www.cms.hhs.gov/esrd/1.asp#9, (2003). “Nothing in this title shall be construed to authorize any Federal officer or employee to exercise any supervision or control over the practice of medicine or the manner in which medical services are provided…” 42 U.S.C. § 1395. The current data would include the patient’s last measured hemoglobin level and the cumulative monthly EPO dose. The previous month’s data would include the previous month’s reported hemoglobin and the cumulative monthly EPO dose. Attachment A Kidney Care Partners Coalition Members Abbott Laboratories Aksys, Ltd. American Kidney Fund American Nephrology Nurses Association American Regent, Inc. Amgen Baxter Healthcare Corporation Bone Care International California Dialysis Council Centers for Dialysis Care DaVita, Inc. Fresenius Medical Care North America Gambro Healthcare/USA Genzyme Medical Education Institute National Kidney Foundation National Renal Administrators Association Northwest Kidney Centers Physicians Dialysis, Inc. Renal Care Group Renal Physicians Association Renal Support Network Satellite Health Care Sigma-Tau Pharmaceuticals, Inc. Watson Pharma, Inc.