We appreciate the concerns raised by Weycker and Barron regarding our study of the effects of sargramostim, filgrastim, and pegfilgrastim on hospitalization risks associated with chemotherapy-induced neutropenia,1 but believe that their criticisms do not call into question the study's conclusions.

We agree that the risk of febrile neutropenia (FN) varies across multiple chemotherapy cycles, so we focused our study design on the use of colony-stimulating factors (CSFs) during the first few chemotherapy cycles, thereby capturing the period with the highest incident risk of FN. Our methodology also took into account the use of CSFs for treatment versus prophylaxis because the adjusted hospitalization incidence rates controlled for the occurrence of a neutropenia diagnosis on the date of CSF initiation, reflecting CSF use for treatment rather than prophylaxis. The results found that pegfilgrastim indeed appears to be used more frequently for prophylaxis than sargramostim and filgrastim, and this potential confounding factor was accounted for in the regression model. Moreover, it is unlikely from a clinical perspective that sargramostim and filgrastim would be used differentially for treatment versus prophylaxis, thereby reducing the likelihood of biased estimates.

With regard to the duration of follow-up across the CSFs, Weycker and Baron appear to imply that the longer observation period penalizes pegfilgrastim (ie, assigns a higher incidence rate of hospitalization to pegfilgrastim). We believe that the longer therapeutic duration of pegfilgrastim compared with sargramostim and filgrastim necessitates a longer observation period and chose 19 days as the average real-life interval between pegfilgrastim administrations. Moreover, the use of patient-years of observation as the denominator for the incidence rate accounts for the longer therapeutic duration.

The matched cohort design was challenged because it excludes the majority of filgrastim and pegfilgrastim patients. Although there are many ways to control for potential confounders, matched cohorts are a well-established research design.2, 3 Indeed, when considering all, rather than matched pairs of CSF patients in the claims data, we found that filgrastim and pegfilgrastim patients tend to be younger (unpublished data). Matching thus reduced the likelihood of confounding due to differences in the age and gender distribution and permitted a better comparison. We agree that further study of this important topic is warranted, but we believe that our analysis and methodology appropriately considered real-world practice and experience.


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  • 1
    Heaney ML, Toy EL, Vekeman F, et al. Comparison of hospitalization risk and associated costs among patients receiving sargramostim, filgrastim, and pegfilgrastim for chemotherapy-induced neutropenia. Cancer. 2009; 115: 4839-4848.
  • 2
    Mann CJ. Observational research methods. Research design II: cohort, cross sectional, and case-control studies. Emerg Med J. 2003; 20: 54-60.
  • 3
    Olson CM, Cummings P, Rivara FP. Association of first- and second-generation air bags with front occupant death in car crashes: a matched cohort study. Am J Epidemiol. 2006; 164: 161-169.

Mark L. Heaney MD, PhD*, Edmond L. Toy PhD†, Francis Vekeman MA‡, * Department of Medicine Memorial Sloan-Kettering Cancer Center New York, New York, † Analysis Group, Inc Lakewood, Colorado, ‡ Analysis Group, Inc Montreal, Quebec, Canada.