Abstract
Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003–2012). Epoetin and darbepoetin use were primary outcomes. Segmented linear regression was used to estimate changes in ESA use levels and trends, clinical appropriateness, and adverse events (VTEs) among chemotherapy-treated cancer patients. To estimate changes in level of drug prescription rate after policy actions, model-specific indicator variables as covariates based on specific actions were included. ESA use fell by 95% and 90% from 2005, for epoetin and darbepoetin, from 22% and 11%, respectively, to 1% and 1%, respectively, among cancer patients with CIA, respectively (p<0.01). Following REMS in 2010, mean hematocrit levels at ESA initiation decreased from 30% to 21% (p<0.01). Black box warnings preceded decreased ESA use among VA cancer patients with CIA. REMS was followed by reduced hematocrit levels at ESA initiation. Our findings contrast with privately- insured and Medicaid insured cancer patient data on chemotherapy-induced anemia where ESA use decreased to 3% to 7% by 2010–2012. By 2012, the era of ESA administration to VA to cancer patients had ended but the warnings remain relevant and significant. In 2019, oncology/hematology national guidelines (ASCO/ASH) recommend that cancer patients with chemotherapy-induced anemia should receive ESAs or red blood cell transfusions after risk-benefit evaluation.
Highlights
Prescription drugs treat diseases and improve patients’ quality of life
Tarlov et al and our study identifies the beginning of marked decrease in Erythropoisis stimulating agent (ESA) use for chemotherapy-induced anemia beginning in 2005, following publications of poorer survival and high venous thromboembolism rates among ESA-treated cancer patients [57]
ESA use fell in the Veterans Administration (VA) system from 2005, even prior to the 2007 Food and Drug Administration (FDA) boxed warnings for epoetin and darbepoetin, a finding that was initially reported by Tarlov et al when evaluating VA use of ESAs between 2002 and 2009 [57]
Summary
Prescription drugs treat diseases and improve patients’ quality of life. no drug is completely safe [1,2]. Food and Drug Administration (FDA) balances risks and benefits by mandating manufacturer disclosure via warnings on product labels. Since 2007, FDA started requiring manufacturers to implement safety efforts, including consent via Risk Evaluation and Monitoring Strategies (REMS) [3,4,5,6,7]. A meta-analysis that public health advisories often led to decreased drug use and fleeting increases in drug monitoring [8]. Public health advisories impact incident, but not prevalent use [9,10]. Boxed warnings are associated with utilization reductions, but substitution between classes occurs [11,12,13,14,15,16,17]. Empirical evidence shows that boxed warnings have mixed results in leading to lower drug utilization. There is a need to identify factors associated with “rapid and sustained responses to risk communications.” [8]
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