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Defense Date


Document Type


Degree Name

Doctor of Philosophy



First Advisor

Dr. David A. Holdford


The American Medical Association (AMA) has estimated that as many as 40 percent of all prescriptions are issued for off-label use. Off-label prescribing is considered to be clinically beneficial and rational in certain life-threatening situations. However, off-label use can pose risks to patients in terms of adverse drug events as well as contribute to rising pharmaceutical costs. The anti-anemic drugs erythropoietin and darbepoetin are costly, and there are significant off-label uses for these drugs some of which are not supported with clinical evidence, hence were selected as study drugs. Our study goals included quantification of the prevalence rate and appropriateness of off-label use of erythropoietin and darbepoetin across U.S. hospitals, and identification of possible predictors of off-label use from the domains of patient characteristics, physician specialty, hospital characteristics and drug characteristics. To address the research questions we performed a retrospective review of 464,834 discharged patients across 515 hospitals who have received erythropoietin and darbepoetin from the time periods between 2001and 2004. The data was supplied by Solucient®. The uses of the two drugs have been categorized using an evidence-based medicine framework that classifies them into: a) on-label use (approved by the FDA), b) off-label use supported (use not approved by FDA but there is strong clinical evidence supporting off-label use), and c) off-label use unsupported (lack of clinical evidence). A multinomial logistic regression model clustered by hospitals was conducted to determine predictors of off-label use. The results of this study revealed that more than half of the utilization of the two erythropoietic drugs is for off-label purposes, the majority of which is supported with evidence. Among the covariates, physician specialty, patient age group, race, drug coverage and length of hospital stay were significant (0.05 level) predictors of off-label use (supported and unsupported) relative to on-label. It is useful to understand the extent and appropriateness of off-label utilization in order to ensure safe and cost-effective use in patients. The availability of empirically derived knowledge on the national level could precipitate the promulgation of more meaningful post-marketing surveillance measures.


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Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

June 2008