Reply to Comparison of hospitalization risk and associated costs among patients receiving sargramostim, filgrastim, and pegfilgrastim for chemotherapy‐induced neutropenia
Bibliographic record
Abstract
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pairs of CSF patients in the claims data, we found that filgrastim and pegfilgrastim patients tend to be younger (unpublished data).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. 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.067 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.014 | 0.013 |
| Insufficient payload (model declined to judge) | 0.007 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".