On-label and off-label prescribing patterns of erythropoiesis-stimulating agents in inpatient hospital settings in the US during the period of major regulatory changes

BackgroundA number of policy and labeling interventions aimed at reducing inappropriate prescribing of erythropoiesis-stimulating agents (ESAs) were implemented in the U.S. between 2006 and 2010. These interventions included the addition of an FDA Black Box Warning to ESA labeling, the implementation of a Risk Evaluation and Mitigation Strategy program, and the adoption of payment restrictions by the Centers for Medicare and Medicaid Services (CMS). The impact of these safety interventions on different types of ESA prescribing (on-label, off-label; evidence-based, not evidence-based) has not been investigated in a single study.ObjectivesThe objective of this study was to explore the prescribing patterns of ESAs for on- and off-label indications in the U.S. hospital inpatients during the period of major policy and labeling changes.MethodsA retrospective analysis of ESAs utilization patterns was conducted using Cerner Health Facts® database from January 1, 2005 to June 30, 2011. The study population consisted of adult patients admitted to hospitals during the study period who received at least one ESAs order. Indications for ESA use were assigned based on ICD-9 CM diagnosis codes, procedure codes, and medication records. ESA use was then classified based on FDA-approval and the strength of scientific evidence supporting its use. Indication categories included (1) on-label use (ONS); (2) off-label use, supported (OFS); and (3) off-label use, unsupported (OFU). Descriptive statistics were used to examine ESA use by patient, hospital, and physician characteristics and over time.ResultsESAs were most frequently prescribed for ONS (48.7%), followed by OFU (42.7%) and OFS indications (8.6%). Of all off-label use, 83.2% were for unsupported indications. Between 2005 and 2010, the percent of inpatient visits with ESA use decreased for supported indications, both on-label (−63.2%) and off-label (−78.2%), but increased for unsupported indications (80%). OFU use surpassed ONS use as the most common type of ESA use in 2009.ConclusionsTotal and ONS ESA use decreased markedly, while OFU ESA use continued to increase during the period of major policy and labeling changes.