- Email: [email protected]
Are Consistency and Individualization Mutually Exclusive in Erythropoiesis-Stimulating Agent Therapy?
Editorial Are Consistency and Individualization Mutually Exclusive in Erythropoiesis-Stimulating Agent Therapy? Related Article, p. 371
A
n essential foundation of continuous quality improvement is the concept that decreasing variability of process leads to improvement in outcomes. The primary purpose of algorithms and care paths is to achieve consistency of process. In treating patients with chronic kidney disease (CKD), there are 4 major factors that have driven the adoption of protocols and the delegation of management details to non-nephrologists such as nurses and pharmacists.1 First, the patient load has increased while the nephrology workforce had remained stable. Second, evidence-based medicine has been embraced and incorporated into these protocols. Third, accountability for outcomes has increased through public reporting and payment. Last, there is an emphasis on continuous quality improvement as a means for achieving improvement in processes and outcomes. In this issue of the American Journal of Kidney Diseases, Aspinall et al2 report that pharmacistmanaged erythropoiesis-stimulating agent (ESA) clinics for patients with non–dialysis-dependent CKD increase the percentage of patients in the target hemoglobin level range of 10-12 g/dL and decrease ESA dose requirements compared with “usual care” administered by a physician. This was a multicenter observational study in 16 Veterans Affairs medical centers involving more than 500 patients. Of the patients in pharmacist-managed ESA clinics, 71.1% had hemoglobin values in the target range versus 56.9% for usualcare sites and 51.7% for usual-care patients at ESA clinic sites. The average monthly dose of darbepoetin was 163 g in pharmacist-managed ESA clinic patients versus 240 g at usual-care sites and 258 g for usual-care patients at ESA clinic sites. For erythropoietin, the respective average 30-day doses were 44,890, 47,181, and 57,436 units. Of note, ESA dose titrations for patients with hemoglobin levels outside the target range occurred approximately twice as often in patients being managed by pharmacists versus those managed by physicians. This study was conducted in 2009, a time when the US Food and Drug Administration (FDA) prescribing information for ESAs recomAddress correspondence to Jay B. Wish, MD, Division of Nephrology, University Hospitals Case Medical Center, 11100 Euclid Ave, Cleveland, OH 44106. E-mail: [email protected] © 2012 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2012.06.007 340
mended a target hemoglobin level of 10-12 g/dL for patients with CKD receiving these agents. A number of previous studies have shown the success of pharmacists in managing patients with CKD with anemia using programs in which pharmacists were responsible for obtaining laboratory tests, adjusting ESA doses, recommending iron therapy, and educating patients—this is the largest such study to date. In their non–dialysis-dependent CKD population, Aspinall et al2 confirm previous observations in patients receiving dialysis that the development of a sound erythropoietin dose titration protocol implemented by nonphysicians (generally “anemia management nurses” in the dialysis unit) can decrease intraand interpatient hemoglobin level variability, achieving a hemoglobin standard deviation of ⬃1.0 g/dL, with ⬃70% of patients within a target hemoglobin range of 10-12 g/dL.3 Because implementation of such protocols by nonphysicians without prescriptive authority is the path of least resistance, the protocols are applied consistently. When physicians with prescriptive authority are involved in ESA dose titration, deviation from the protocol is common because such physicians think the patient is an “exception.” Thus, inconsistent processes lead to inconsistent outcomes, and hemoglobin level variability increases. Substituting pharmacists for anemia management nurses and non–dialysisdependent CKD for end-stage renal disease treated by dialysis, this study demonstrates the same principle. When the study by Aspinall et al2 was conducted, decreasing hemoglobin level variability (that is, achieving consistency) and maximizing the percentage of patients within a “one-size-fits-all” target hemoglobin range of 10-12 g/dL was the desired outcome. However, in 2011, the FDA recommended removing the hemoglobin target range of 10-12 g/dL for ESA therapy in patients with CKD and recommended initiating ESA therapy (on an “individualized” basis) only when hemoglobin level is ⬍10 g/dL. The FDA further suggested that ESA therapy be decreased or discontinued when hemoglobin level is ⬎10 g/dL in patients with non–dialysis-dependent CKD and when hemoglobin level is ⬎11 g/dL in patients treated with dialysis. In both groups, the ESA dose should be the minimal amount to avoid transfusions.4 These days, standardization (uniform protocol implementation) is out and individualization of therapy is in. Is this change compatible with delegation of an anemia management protocol to nonphysicians such as pharmacists and nurses? Aspinall et al2 maintain that it is and they recommend that the pharmacist and Am J Kidney Dis. 2012;60(3):340-342
Editorial
physician work together to determine the lowest acceptable hemoglobin level for each patient to minimize the symptoms of anemia and avoid transfusions.2 To date, it does not appear as if avoidance of transfusions, the only benefit of ESA therapy acknowledged by the FDA for dialysis patients, is being maintained in the post-2011 era. In yet-to-be published data from the US Renal Data System, the transfusion rate for dialysis patients has increased significantly since the beginning of 2011.5 As reported at the 2012 National Kidney Foundation Spring Clinical Meetings, in each of the first 9 months of 2011, the share of dialysis patients covered by Medicare who received blood transfusions increased by 9%-22% over the corresponding months in 2010. In September 2012, there were 10,041 transfusions for dialysis patients compared with 8,259 for the same month in 2010. On the contrary, there was virtually no change in transfusion rates in 2009-2010. Can individualization of anemia management be operationalized successfully in the real world? Ironically, I wrote an editorial for AJKD 1 year ago posing what may appear to be the opposite question: “Hemoglobin Variability as a Predictor of Mortality: What’s a Practitioner to Do?”3 Although consistency is the opposite of variability, it is not the opposite of individualization (whose counterpoint is standardization). The question then is whether individualized therapy for anemia can be applied consistently. Kliger et al6 argue that it can if patient-reported outcomes are used to set ESA treatment in those with CKD-associated anemia. They suggest that anemia treatment aim to improve the aspects of patients’ quality of life that are affected most by anemia rather than try to get all patients to achieve the same target hemoglobin level. Individual
patients could use their own perceptions of quality of life to prioritize the benefits and risks of ESA treatment. This technique would help physicians and patients weigh the importance of avoiding transfusion and allow them to develop a personal hemoglobin level target range that could be incorporated into an ESA dose-titration algorithm consistently applied by a nonphysician. Such an approach achieves both consistency and individualization. Of course, operating multiple concurrent ESA dose-titration protocols within a facility will increase interpatient hemoglobin level variability but decrease intrapatient hemoglobin level variability. Of the 2, intrapatient hemoglobin level variability seems to be the greater predictor of adverse outcomes.3 The widespread application of physician-ordered, pilot-tested, validated, nonphysician-implemented ESA dose-titration protocols has been associated with a progressive decrease in the hemoglobin level standard deviation in dialysis patients in the United States, from 1.48 in 2006 to 1.35 in 2009 according to monthly claims data.7 The Elab project collects laboratory data from all dialysis facilities or their laboratories during the fourth quarter of every year. One hemoglobin value is collected for each month in the quarter and the 3 values are averaged; thus, hemoglobin level standard deviations in the Elab project will be less than those in claims, which represent single monthly hemoglobin values. Figure 1 shows hemoglobin data from Elab with hemoglobin level distribution curves from 2006 through 2010.8 Despite changes in clinical practice guidelines for anemia management, FDA guidance regarding hemoglobin level targets for patients receiving ESAs, and Centers for Medicare & Medicaid Services reimbursement policy for ESAs, the hemoglobin level distribution curve shifted to the
45% Mean +/- SD Hemoglobin (g/dL)
40%
Oct - Dec 2006 Oct - Dec 2007 Oct - Dec 2008 Oct - Dec 2009 Oct - Dec 2010
Percent of Paents
35% 30%
12.04 +/- 1.21 11.86 +/- 1.15 11.68 +/- 1.06 11.59 +/- 1.03 11.46 +/- 1.00
Q4 2006
25%
Q4 2007
20%
Q4 2008 Q4 2009
15%
Q4 2010
10% Figure 1. Hemoglobin level distribution in hemodialysis patients, 2006-2010. Data from each patient represent the average of 3 monthly values from the fourth quarter (Q4) of each year. Abbreviation: SD, standard deviation. Reproduced with permission from Renal Network of the Upper Midwest, Inc.8 Am J Kidney Dis. 2012;60(3):340-342
5% 0% 7
8
9
10
11
12
13
14
15
16
17
Mean Hemoglobin (g/dL)
341
Jay B. Wish
left between 2008 and 2010 but did not change its shape or standard deviation. This finding implies that dialysis providers responded to the evolving anemia treatment landscape by adjusting the ESA dosetitration triggers in their anemia management protocols, but did not change the penetration of those nonphysician-administered protocols in their facilities. Accordingly, it seems feasible for dialysis providers to maintain a library of ESA dose-titration protocols with customized hemoglobin level targets that could be individualized to address the risk versus benefit of ESA therapy for each patient. The National Institute for Clinical Health and Excellence (NICE) of the United Kingdom released its guideline for anemia management for patients with CKD in 2011; they continue to recommend a hemoglobin level target of 10-12 g/dL for adult patients treated with ESAs.9 The NICE guideline also includes an anemia management algorithm to assist in the uniform application of its recommendations. The upcoming KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for anemia in CKD, which supersedes previous KDOQI (Kidney Disease Outcomes Quality Initiative) anemia guidelines, will recommend individualizing the decision of whether to initiate ESA therapy in patients with non–dialysisdependent CKD based on the risks related to ESA therapy and each patient’s rate of hemoglobin level decline, previous response to iron therapy, risk of needing a transfusion, and presence of symptoms attributable to anemia. For adult patients with CKD treated with dialysis, KDIGO suggests that ESA therapy be used to prevent the patient’s hemoglobin level from decreasing to ⬍9 g/dL by starting ESA therapy when hemoglobin level is 9-10 g/dL. KDIGO notes that individualizing therapy is reasonable because some patients may have improvements in quality of life at higher hemoglobin concentrations and ESA therapy may be started at a hemoglobin level ⬎10 g/dL. In general, KDIGO suggests that ESAs not be used to maintain hemoglobin levels at ⬎11.5 g/dL. In summary, the goal of individualizing anemia management can still be achieved by the consistent application of ESA dose-titration protocols by nonphysicians. The floor and ceiling target hemoglobin levels for each patient can be individualized by the physician based on patient-specific factors, including comorbid
342
conditions, symptoms of anemia, level of physical activity, and importance of avoiding transfusion. Then a patient-specific protocol can be implemented by a nonphysician for ESA dose titration to minimize intrapatient hemoglobin level variability by keeping the process consistent (ie, keeping the physician from deviating from the protocol). The increase in transfusions in dialysis patients in the United States during 2011 is troubling, but the full reconciliation of consistency and individualization with regard to anemia management has yet to occur. Jay B. Wish, MD University Hospitals Case Medical Center Cleveland, Ohio
ACKNOWLEDGEMENTS Financial Disclosure: Dr Wish is a consultant and on the speakers bureaus for Affymax (peginesatide) and AMAG (ferumoxytol).
REFERENCES 1. Wish JB, Blondin J. Algorithms and care paths for quality improvement. In: Owen WF, Pereira BJG, Sayegh MH, eds. Dialysis and Transplantation. A Companion to Brenner & Rector’s The Kidney. Philadelphia, PA: WB Saunders Co; 2000. 2. Aspinall SL, Cunningham FE, Zhao X, et al. Impact of pharmacist-managed erythropoiesis-stimulating agents clinics for patients with non–dialysis-dependent CKD. Am J Kidney Dis. 2012;60:371-379. 3. Wish JB. Hemoglobin variability as a predictor of mortality: what’s a practitioner to do? Am J Kidney Dis. 2011;57:190-193. 4. Amgen. PROCRIT (epoetin alfa) [prescribing information]. Thousand Oaks, CA: Amgen; 2011. http://www.procrit.com/sites/ default/files/pdf/ProcritBooklet.pdf. Accessed May 20, 2012. 5. Sack K. Unintended consequence for dialysis patients as drug rule changes. New York Times. http://www.nytimes.com/2012/ 05/11/health/policy/dialysis-rule-changes-followed-by-transfusionincreases.html?_r⫽1 . Accessed May 20, 2012. 6. Kliger AS, Fishbane S, Finkelstein FO. Erythropoietic stimulating agents and quality of a patient’s life: individualizing anemia treatment. Clin J Am Soc Nephrol. 2012;7:354-357. 7. Spiegel DM, Khan I, Krishnan M, Mayne TJ. Changes in hemoglobin level distribution in US dialysis patients from June 2006 to November 2008. Am J Kidney Dis. 2010;55:113-120. 8. Renal Network of the Upper Midwest, Inc. Elab project: national 2010 and trends. http://www.esrdnet11.org/Elab/elab_ national_2010_and_trends_report.pdf. Accessed June 5, 2012. 9. National Institute for Health and Clinical Excellence. Anemia management for people with chronic kidney disease. Issue date February 2011. http://www.nice.org.uk/nicemedia/live/13329/ 52853/52853.pdf. Accessed May 20, 2012.
Am J Kidney Dis. 2012;60(3):340-342
A
n essential foundation of continuous quality improvement is the concept that decreasing variability of process leads to improvement in outcomes. The primary purpose of algorithms and care paths is to achieve consistency of process. In treating patients with chronic kidney disease (CKD), there are 4 major factors that have driven the adoption of protocols and the delegation of management details to non-nephrologists such as nurses and pharmacists.1 First, the patient load has increased while the nephrology workforce had remained stable. Second, evidence-based medicine has been embraced and incorporated into these protocols. Third, accountability for outcomes has increased through public reporting and payment. Last, there is an emphasis on continuous quality improvement as a means for achieving improvement in processes and outcomes. In this issue of the American Journal of Kidney Diseases, Aspinall et al2 report that pharmacistmanaged erythropoiesis-stimulating agent (ESA) clinics for patients with non–dialysis-dependent CKD increase the percentage of patients in the target hemoglobin level range of 10-12 g/dL and decrease ESA dose requirements compared with “usual care” administered by a physician. This was a multicenter observational study in 16 Veterans Affairs medical centers involving more than 500 patients. Of the patients in pharmacist-managed ESA clinics, 71.1% had hemoglobin values in the target range versus 56.9% for usualcare sites and 51.7% for usual-care patients at ESA clinic sites. The average monthly dose of darbepoetin was 163 g in pharmacist-managed ESA clinic patients versus 240 g at usual-care sites and 258 g for usual-care patients at ESA clinic sites. For erythropoietin, the respective average 30-day doses were 44,890, 47,181, and 57,436 units. Of note, ESA dose titrations for patients with hemoglobin levels outside the target range occurred approximately twice as often in patients being managed by pharmacists versus those managed by physicians. This study was conducted in 2009, a time when the US Food and Drug Administration (FDA) prescribing information for ESAs recomAddress correspondence to Jay B. Wish, MD, Division of Nephrology, University Hospitals Case Medical Center, 11100 Euclid Ave, Cleveland, OH 44106. E-mail: [email protected] © 2012 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2012.06.007 340
mended a target hemoglobin level of 10-12 g/dL for patients with CKD receiving these agents. A number of previous studies have shown the success of pharmacists in managing patients with CKD with anemia using programs in which pharmacists were responsible for obtaining laboratory tests, adjusting ESA doses, recommending iron therapy, and educating patients—this is the largest such study to date. In their non–dialysis-dependent CKD population, Aspinall et al2 confirm previous observations in patients receiving dialysis that the development of a sound erythropoietin dose titration protocol implemented by nonphysicians (generally “anemia management nurses” in the dialysis unit) can decrease intraand interpatient hemoglobin level variability, achieving a hemoglobin standard deviation of ⬃1.0 g/dL, with ⬃70% of patients within a target hemoglobin range of 10-12 g/dL.3 Because implementation of such protocols by nonphysicians without prescriptive authority is the path of least resistance, the protocols are applied consistently. When physicians with prescriptive authority are involved in ESA dose titration, deviation from the protocol is common because such physicians think the patient is an “exception.” Thus, inconsistent processes lead to inconsistent outcomes, and hemoglobin level variability increases. Substituting pharmacists for anemia management nurses and non–dialysisdependent CKD for end-stage renal disease treated by dialysis, this study demonstrates the same principle. When the study by Aspinall et al2 was conducted, decreasing hemoglobin level variability (that is, achieving consistency) and maximizing the percentage of patients within a “one-size-fits-all” target hemoglobin range of 10-12 g/dL was the desired outcome. However, in 2011, the FDA recommended removing the hemoglobin target range of 10-12 g/dL for ESA therapy in patients with CKD and recommended initiating ESA therapy (on an “individualized” basis) only when hemoglobin level is ⬍10 g/dL. The FDA further suggested that ESA therapy be decreased or discontinued when hemoglobin level is ⬎10 g/dL in patients with non–dialysis-dependent CKD and when hemoglobin level is ⬎11 g/dL in patients treated with dialysis. In both groups, the ESA dose should be the minimal amount to avoid transfusions.4 These days, standardization (uniform protocol implementation) is out and individualization of therapy is in. Is this change compatible with delegation of an anemia management protocol to nonphysicians such as pharmacists and nurses? Aspinall et al2 maintain that it is and they recommend that the pharmacist and Am J Kidney Dis. 2012;60(3):340-342
Editorial
physician work together to determine the lowest acceptable hemoglobin level for each patient to minimize the symptoms of anemia and avoid transfusions.2 To date, it does not appear as if avoidance of transfusions, the only benefit of ESA therapy acknowledged by the FDA for dialysis patients, is being maintained in the post-2011 era. In yet-to-be published data from the US Renal Data System, the transfusion rate for dialysis patients has increased significantly since the beginning of 2011.5 As reported at the 2012 National Kidney Foundation Spring Clinical Meetings, in each of the first 9 months of 2011, the share of dialysis patients covered by Medicare who received blood transfusions increased by 9%-22% over the corresponding months in 2010. In September 2012, there were 10,041 transfusions for dialysis patients compared with 8,259 for the same month in 2010. On the contrary, there was virtually no change in transfusion rates in 2009-2010. Can individualization of anemia management be operationalized successfully in the real world? Ironically, I wrote an editorial for AJKD 1 year ago posing what may appear to be the opposite question: “Hemoglobin Variability as a Predictor of Mortality: What’s a Practitioner to Do?”3 Although consistency is the opposite of variability, it is not the opposite of individualization (whose counterpoint is standardization). The question then is whether individualized therapy for anemia can be applied consistently. Kliger et al6 argue that it can if patient-reported outcomes are used to set ESA treatment in those with CKD-associated anemia. They suggest that anemia treatment aim to improve the aspects of patients’ quality of life that are affected most by anemia rather than try to get all patients to achieve the same target hemoglobin level. Individual
patients could use their own perceptions of quality of life to prioritize the benefits and risks of ESA treatment. This technique would help physicians and patients weigh the importance of avoiding transfusion and allow them to develop a personal hemoglobin level target range that could be incorporated into an ESA dose-titration algorithm consistently applied by a nonphysician. Such an approach achieves both consistency and individualization. Of course, operating multiple concurrent ESA dose-titration protocols within a facility will increase interpatient hemoglobin level variability but decrease intrapatient hemoglobin level variability. Of the 2, intrapatient hemoglobin level variability seems to be the greater predictor of adverse outcomes.3 The widespread application of physician-ordered, pilot-tested, validated, nonphysician-implemented ESA dose-titration protocols has been associated with a progressive decrease in the hemoglobin level standard deviation in dialysis patients in the United States, from 1.48 in 2006 to 1.35 in 2009 according to monthly claims data.7 The Elab project collects laboratory data from all dialysis facilities or their laboratories during the fourth quarter of every year. One hemoglobin value is collected for each month in the quarter and the 3 values are averaged; thus, hemoglobin level standard deviations in the Elab project will be less than those in claims, which represent single monthly hemoglobin values. Figure 1 shows hemoglobin data from Elab with hemoglobin level distribution curves from 2006 through 2010.8 Despite changes in clinical practice guidelines for anemia management, FDA guidance regarding hemoglobin level targets for patients receiving ESAs, and Centers for Medicare & Medicaid Services reimbursement policy for ESAs, the hemoglobin level distribution curve shifted to the
45% Mean +/- SD Hemoglobin (g/dL)
40%
Oct - Dec 2006 Oct - Dec 2007 Oct - Dec 2008 Oct - Dec 2009 Oct - Dec 2010
Percent of Paents
35% 30%
12.04 +/- 1.21 11.86 +/- 1.15 11.68 +/- 1.06 11.59 +/- 1.03 11.46 +/- 1.00
Q4 2006
25%
Q4 2007
20%
Q4 2008 Q4 2009
15%
Q4 2010
10% Figure 1. Hemoglobin level distribution in hemodialysis patients, 2006-2010. Data from each patient represent the average of 3 monthly values from the fourth quarter (Q4) of each year. Abbreviation: SD, standard deviation. Reproduced with permission from Renal Network of the Upper Midwest, Inc.8 Am J Kidney Dis. 2012;60(3):340-342
5% 0% 7
8
9
10
11
12
13
14
15
16
17
Mean Hemoglobin (g/dL)
341
Jay B. Wish
left between 2008 and 2010 but did not change its shape or standard deviation. This finding implies that dialysis providers responded to the evolving anemia treatment landscape by adjusting the ESA dosetitration triggers in their anemia management protocols, but did not change the penetration of those nonphysician-administered protocols in their facilities. Accordingly, it seems feasible for dialysis providers to maintain a library of ESA dose-titration protocols with customized hemoglobin level targets that could be individualized to address the risk versus benefit of ESA therapy for each patient. The National Institute for Clinical Health and Excellence (NICE) of the United Kingdom released its guideline for anemia management for patients with CKD in 2011; they continue to recommend a hemoglobin level target of 10-12 g/dL for adult patients treated with ESAs.9 The NICE guideline also includes an anemia management algorithm to assist in the uniform application of its recommendations. The upcoming KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for anemia in CKD, which supersedes previous KDOQI (Kidney Disease Outcomes Quality Initiative) anemia guidelines, will recommend individualizing the decision of whether to initiate ESA therapy in patients with non–dialysisdependent CKD based on the risks related to ESA therapy and each patient’s rate of hemoglobin level decline, previous response to iron therapy, risk of needing a transfusion, and presence of symptoms attributable to anemia. For adult patients with CKD treated with dialysis, KDIGO suggests that ESA therapy be used to prevent the patient’s hemoglobin level from decreasing to ⬍9 g/dL by starting ESA therapy when hemoglobin level is 9-10 g/dL. KDIGO notes that individualizing therapy is reasonable because some patients may have improvements in quality of life at higher hemoglobin concentrations and ESA therapy may be started at a hemoglobin level ⬎10 g/dL. In general, KDIGO suggests that ESAs not be used to maintain hemoglobin levels at ⬎11.5 g/dL. In summary, the goal of individualizing anemia management can still be achieved by the consistent application of ESA dose-titration protocols by nonphysicians. The floor and ceiling target hemoglobin levels for each patient can be individualized by the physician based on patient-specific factors, including comorbid
342
conditions, symptoms of anemia, level of physical activity, and importance of avoiding transfusion. Then a patient-specific protocol can be implemented by a nonphysician for ESA dose titration to minimize intrapatient hemoglobin level variability by keeping the process consistent (ie, keeping the physician from deviating from the protocol). The increase in transfusions in dialysis patients in the United States during 2011 is troubling, but the full reconciliation of consistency and individualization with regard to anemia management has yet to occur. Jay B. Wish, MD University Hospitals Case Medical Center Cleveland, Ohio
ACKNOWLEDGEMENTS Financial Disclosure: Dr Wish is a consultant and on the speakers bureaus for Affymax (peginesatide) and AMAG (ferumoxytol).
REFERENCES 1. Wish JB, Blondin J. Algorithms and care paths for quality improvement. In: Owen WF, Pereira BJG, Sayegh MH, eds. Dialysis and Transplantation. A Companion to Brenner & Rector’s The Kidney. Philadelphia, PA: WB Saunders Co; 2000. 2. Aspinall SL, Cunningham FE, Zhao X, et al. Impact of pharmacist-managed erythropoiesis-stimulating agents clinics for patients with non–dialysis-dependent CKD. Am J Kidney Dis. 2012;60:371-379. 3. Wish JB. Hemoglobin variability as a predictor of mortality: what’s a practitioner to do? Am J Kidney Dis. 2011;57:190-193. 4. Amgen. PROCRIT (epoetin alfa) [prescribing information]. Thousand Oaks, CA: Amgen; 2011. http://www.procrit.com/sites/ default/files/pdf/ProcritBooklet.pdf. Accessed May 20, 2012. 5. Sack K. Unintended consequence for dialysis patients as drug rule changes. New York Times. http://www.nytimes.com/2012/ 05/11/health/policy/dialysis-rule-changes-followed-by-transfusionincreases.html?_r⫽1 . Accessed May 20, 2012. 6. Kliger AS, Fishbane S, Finkelstein FO. Erythropoietic stimulating agents and quality of a patient’s life: individualizing anemia treatment. Clin J Am Soc Nephrol. 2012;7:354-357. 7. Spiegel DM, Khan I, Krishnan M, Mayne TJ. Changes in hemoglobin level distribution in US dialysis patients from June 2006 to November 2008. Am J Kidney Dis. 2010;55:113-120. 8. Renal Network of the Upper Midwest, Inc. Elab project: national 2010 and trends. http://www.esrdnet11.org/Elab/elab_ national_2010_and_trends_report.pdf. Accessed June 5, 2012. 9. National Institute for Health and Clinical Excellence. Anemia management for people with chronic kidney disease. Issue date February 2011. http://www.nice.org.uk/nicemedia/live/13329/ 52853/52853.pdf. Accessed May 20, 2012.
Am J Kidney Dis. 2012;60(3):340-342