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IIR 08-354 – HSR&D Study

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IIR 08-354
Clinical Guidelines for ESA Use in Cancer: Impacts on Clinical Practice
Denise M. Hynes PhD MPH BSN
Edward Hines Jr. VA Hospital, Hines, IL
Hines, IL
Funding Period: April 2009 - March 2012

BACKGROUND/RATIONALE:
The use of erythropoiesis-stimulating agents (ESAs) has proven effective in reducing the need for blood transfusions to manage anemia in cancer patients. However, studies indicating an association between ESA use and higher rates of thrombotic vascular events, tumor promotion, and reduced survival have raised concerns about the use of ESAs. Since late 2006, product labeling regarding ESA usage has been updated to incorporate this emerging information. In March 2007, the FDA added a "black box warning" to ESA product labeling to advise that these products should be given to cancer patients only to maintain a hemoglobin (Hb) level sufficient to avoid transfusion.

Although new information about effects of ESAs in cancer care, changes in clinical guidelines from three professional organizations, and a major healthcare change in coverage by the Centers for Medicare & Medicaid Services have been broadly disseminated, few published works have addressed the impact of these changes on treatment. Recent evidence suggests wide variation in the use of ESAs in cancer but information about factors associated with prescription and use of ESAs is lacking.

OBJECTIVE(S):
The objective of this study was to contribute new information about patterns of ESA use and associated adverse events in a general oncology population: veterans treated for cancer in the VHA, where approximately 40,000 patients are diagnosed with cancer annually.

Specific research aims were to examine among veterans with cancer, the: (1) impact of changes in clinical guidelines for anemia management in cancer on practice patterns and healthcare costs over time; (2) associations between ESA use and adverse events (death or a thromboembolic event) and the factors that contribute to the occurrence of adverse events.

METHODS:
For this retrospective cohort study, subjects were identified from VA cancer registry records. There were 257,498 patients who had an incident and invasive cancer diagnosis between 1/1/2002 and 12/31/2009 and were active VA healthcare users. Data sources included national VA cancer registry data (Patient Care Services), national workload and clinical data (National Data Systems), electronic health record data (nationally via VistAWeb), pharmacy data (Pharmacy Benefits Management), Health Economic Resource Center (HERC) average cost data files, and Medicare claims data through the VA Information Resource Center (VIReC).

We have undertaken four major analyses: (1) Trends in Anemia Management Before and After the Guidelines, (2) Severity of Anemia that Triggers ESA Treatment, (3) Costs of Anemia Treatment relative to Other Aspects of Cancer Care, and (4) Adverse Events due to ESA Treatment, including pulmonary embolism, deep vein thrombosis, and stroke. We defined the period before the guideline changes (PRE) (2002-2006) and after (POST) (2007-2009).

FINDINGS/RESULTS:
1) Trends in Anemia Management: Among 17,014 and 4,225 lung and colon cancer patients treated between 2002 and 2008, ESA use was lower in the POST period compared to the PRE period (lung: 21% vs. 36%, colon: 12% vs. 20%). Those who were treated in the POST period had 65% (lung OR 0.35, 95% CI: 0.30-0.42) and 53% (colon OR 0.47, 95% CL: 0.36-0.63) reduced odds of ESA treatment compared to those treated before. Declines in predicted probabilities of ESA use began in 2006.

2) Severity of Anemia that Triggers ESA Treatment: Among 7,700 patients who had been prescribed an ESA within 12 months of diagnosis, had received chemotherapy, and had complete Hb data, 24% of patients were treated in the POST period and the average triggering Hb level was 0.66 g/dL lower in the POST period compared to the PRE period (95% CI: -0.76 to -0.56). The decline in the hemoglobin level that triggered treatment with ESA began in 2006.

3) Costs of Anemia Treatment: Among 13,985 lung (9,894 from the PRE and 4,091 from the POST periods) and 3,227 colon (2,278 from the PRE and 949 from the POST periods) cancer patients, preliminary results show that the mean total costs of health care are significantly lower for both lung and colon cancer patients in the PRE compared to the POST period. This difference may be due to increases in outpatient costs and requires further exploration.

4) Risk of Thromboembolic Events Associated with ESAs: Among 35,246 lung and 10,762 colon cancer patients, 13.1% and 12.8% experienced a pulmonary embolism, deep vein thrombosis, or stroke, respectively. Among these cancer patients followed until they experienced any of three thromboembolic events or until the end of their study period, ESA exposure was associated with an increased risk in both the lung (adjusted HR 1.18, 95% CI: 1.02-1.36) and colon (adjusted HR 1.71, 95% CI: 1.29-2.26) cancer groups.

IMPACT:
The fact that declines in use of ESAs and Hb levels triggering their use have been found in both VA and private-sector settings suggests that the VA is not singular in its trend despite having a unique organizational structure, population and financial incentives. Potential cost implications of shifts in ESA use for the VA, which spent over $3.8 billion on pharmaceuticals in FY2009, are enormous. A recent analysis identified ESAs as among the highest cost pharmaceuticals dispensed in the VA, so increases and decreases in use may have large budgetary impacts.

PUBLICATIONS:

Journal Articles

  1. Stroupe KT, Tarlov E, Weichle TW, Zhang QL, Michaelis LC, Ozer H, Durazo-Arvizu R, Hynes DM. Costs of care for lung and colon cancer patients receiving chemotherapy following FDA policy changes. Supportive Care in Cancer : Official Journal of The Multinational Association of Supportive Care in Cancer. 2014 Dec 1; 22(12):3153-63.
  2. Stroupe KT, Tarlov E, Lee TA, Weichle TW, Zhang QL, Michaelis LC, Ozer H, Durazo-Arvizu R, Browning MM, Hynes DM. Hemoglobin levels triggering erythropoiesis-stimulating agent therapy in patients with cancer: the shift after United States Food and Drug Administration policy changes. Pharmacotherapy. 2012 Nov 1; 32(11):988-97.
  3. Tarlov E, Stroupe KT, Lee TA, Weichle TW, Zhang QL, Michaelis LC, Ozer H, Browning MM, Hynes DM. Trends in anemia management in lung and colon cancer patients in the US Department of Veterans Affairs, 2002-2008. Supportive Care in Cancer : Official Journal of The Multinational Association of Supportive Care in Cancer. 2012 Aug 1; 20(8):1649-57.
Conference Presentations

  1. Stroupe KT, Tarlov E, Lee TA, Weichle TW, Zhang Q, Michaelis LC, Ozer H, Browning M, Hynes DM. Trends in Anemia Treatment in Cancer, 2002 - 2009. Paper presented at: VA HSR&D National Meeting; 2012 Jul 18; National Harbor, MD.
  2. Tarlov E, Stroupe KT, Lee TA, Zhang Q, Weichle TW, Ozer H, Michaelis L, Hynes DM. Health Policy Changes, Information Dissemination, and Shifts in Anemia Treatment in Lung and Colon Cancer, 2002-2008. Poster session presented at: AcademyHealth Annual Research Meeting; 2011 Jun 12; Seattle, WA.
  3. Tarlov E, Stroupe KT, Lee TA, Zhang Q, Weichle TW, Browning M, Hynes DM. Erythropoietin Use in VA Cancer Care: Shifts in the Treatment of Lung and Colon Cancer, 2002- 2008. Poster session presented at: Gerontological Society of America Annual Scientific Meeting; 2010 Nov 20; New Orleans, LA.


DRA: Health Systems, Cancer
DRE: none
Keywords: Cost, Cost-Effectiveness, Guideline Development and Implementation, Practice Patterns/Trends, Adverse Event Monitoring, Adverse events, Cancer
MeSH Terms: none

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