Influence of safety warnings on ESA prescribing among dialysis patients using an interrupted time series

Abstract

Background: In March, 2007, a black box warning was issued by the Food and Drug Administration (FDA) to use the lowest possible erythropoiesis-stimulating agents (ESA) doses for treatment of anemia associated with renal disease. The goal is to determine if a change in ESA use was observed following the warning among US dialysis patients.

Methods: ESA therapy was examined from September 2004 through August 2009 (thirty months before and after the FDA black box warning) among adult Medicare hemodialysis patients. An interrupted time series model assessed the impact of the warnings.

Results: The FDA black box warning did not appear to influence ESA prescribing among the overall dialysis population. However, significant declines in ESA therapy after the FDA warnings were observed for selected populations. Patients with a hematocrit≥36% had a declining month-to-month trend before (-164 units/week, p=<0.0001) and after the warnings (-80 units/week, p=.001), and a large drop in ESA level immediately after the black box (-4,744 units/week, p=<.0001). Not-for-profit facilities had a declining month-to-month trend before the warnings (-90 units/week, p=.009) and a large drop in ESA dose immediately afterwards (-2,487 units/week, p=0.015). In contrast, for-profit facilities did not have a significant change in ESA prescribing.

Conclusions: ESA therapy had been both profitable for providers and controversial regarding benefits for nearly two decades. The extent to which a FDA black box warning highlighting important safety concerns influenced use of ESA therapy among nephrologists and dialysis providers was unknown. Our study found no evidence of changes in ESA prescribing for the overall dialysis population resulting from a FDA black box warning.

Figure 1

ESA units/week per month for the US hemodialysis population from September 2004 to August 2009.

Figure 2

ESA units/week per month for the US hemodialysis population from September 2004 to August 2009 by hematocrit level. Given the different dosing levels based on hematocrit level, we used a different scale for the Y axis for each hematocrit category, although each covered a range of ~10,000 ESA units.

Figure 3

ESA units/week per month for the US hemodialysis population from September 2004 to August 2009 by facility organizational status. The straight solid line is for the trend derived from the interrupted time series regression model, the cross (+) is the observed value and the diamond (♦) is the predicted value based on the interrupted time series model. The model parameters for all figures are presented in Table 3.