Effects of the US Food and Drug Administration Boxed Warning of Erythropoietin-Stimulating Agents on Utilization and Adverse Outcome
A partir des données des registres américains des cancers et de la base Medicare, cette étude analyse l'impact, sur l'utilisation de ces médicaments et sur la survenue d'événements indésirables, des avertissements imposés par la "Food and Drug Administration" sur les boîtes d'agents stimulant l'érythropoïétine utilisés pour traiter une anémie induite par une chimiothérapie
Purpose : In March 2007, a US Food and Drug Administration boxed warning was issued for erythropoietin-stimulating agents (ESAs) regarding serious adverse events, such as venous thromboembolism (VTE). We evaluated the US Food and Drug Administration’s boxed warning of ESAs used to treat chemotherapy-induced anemia because evidence on the effectiveness of boxed warnings remains inconclusive. Patients and Methods : Using 2004 to 2009 SEER-Medicare data, we exploited a natural experiment to examine the effects of ESA boxed warnings on utilization and risk of VTE. The intervention group included Medicare fee-for-services patients diagnosed with colorectal, breast, or lung cancers targeted by this warning and undergoing chemotherapy; the control group included patients with myelodysplastic syndromes not targeted by this warning. The period from January 2004 to September 2006 was used as the prewarning period; the period from April 2007 to September 2009 was used as the postwarning period. The two binary dependent variables included ESA use and hospitalized VTE. Linear probability models with a difference-in-differences specification were used for estimation. Results : Our sample consisted of 45,319 unique patients between 2004 and 2009. The trends in ESA use remained similar between the intervention and control groups before the warning, but started declining sharply in the intervention group only after the warning. The trends in hospitalized VTE were relatively stable. Regressions showed that the ESA boxed warning was associated with a 20.2-percentage-point reduction (P < .001) in the likelihood of ESAs being used to treat cancers targeted by the warning, but not significantly associated with the likelihood of hospitalized VTE. Conclusion : Our study showed that the warning was effective in reducing ESA utilization. Future studies should examine other regulatory drug safety actions, such as the Risk Evaluation and Mitigation Strategy initiative, whose effectiveness remains unknown.