Effects of a Guideline-Informed Clinical Decision Support System Intervention to Improve Colony-Stimulating Factor Prescribing: A Cluster Randomized Clinical Trial

Abstract

Importance: Colony-stimulating factors are prescribed to patients undergoing chemotherapy to reduce the risk of febrile neutropenia. Research suggests that 55% to 95% of colony-stimulating factor prescribing is inconsistent with national guidelines.

Objective: To examine whether a guideline-based standing order for primary prophylactic colony-stimulating factors improves use and reduces the incidence of febrile neutropenia.

Design, setting, and participants: This cluster randomized clinical trial, the Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER), involved 32 community oncology clinics in the US. Participants were adult patients with breast, colorectal, or non-small cell lung cancer initiating cancer therapy and enrolled between January 2016 and April 2020. Data analysis was performed from July to October 2021.

Interventions: Sites were randomized 3:1 to implementation of a guideline-based primary prophylactic colony-stimulating factor standing order system or usual care. Automated orders were added for high-risk regimens, and an alert not to prescribe was included for low-risk regimens. Risk was based on National Comprehensive Cancer Network guidelines.

Main outcomes and measures: The primary outcome was to find an increase in colony-stimulating factor use among high-risk patients from 40% to 75%, a reduction in use among low-risk patients from 17% to 7%, and a 50% reduction in febrile neutropenia rates in the intervention group. Mixed model logistic regression adjusted for correlation of outcomes within a clinic.

Results: A total of 2946 patients (median [IQR] age, 59.0 [50.0-67.0] years; 2233 women [77.0%]; 2292 White [79.1%]) were enrolled; 2287 were randomized to the intervention, and 659 were randomized to usual care. Colony-stimulating factor use for patients receiving high-risk regimens was high and not significantly different between groups (847 of 950 patients [89.2%] in the intervention group vs 296 of 309 patients [95.8%] in the usual care group). Among high-risk patients, febrile neutropenia rates for the intervention (58 of 947 patients [6.1%]) and usual care (13 of 308 patients [4.2%]) groups were not significantly different. The febrile neutropenia rate for patients receiving high-risk regimens not receiving colony-stimulating factors was 14.9% (17 of 114 patients). Among the 585 patients receiving low-risk regimens, colony-stimulating factor use was low and did not differ between groups (29 of 457 patients [6.3%] in the intervention group vs 7 of 128 patients [5.5%] in the usual care group). Febrile neutropenia rates did not differ between usual care (1 of 127 patients [0.8%]) and the intervention (7 of 452 patients [1.5%]) groups.

Conclusions and relevance: In this cluster randomized clinical trial, implementation of a guideline-informed standing order did not affect colony-stimulating factor use or febrile neutropenia rates in high-risk and low-risk patients. Overall, use was generally appropriate for the level of risk. Standing order interventions do not appear to be necessary or effective in the setting of prophylactic colony-stimulating factor prescribing.

Trial registration: ClinicalTrials.gov Identifier: NCT02728596.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Ramsey reported having consulting or advisory roles with Bayer Corporation, Bristol-Myers Squibb, AstraZeneca, Merck & Company Inc, Pfizer, Seattle Genetics, Biovica, and Genentech; receiving research funding from Bayer Corporation and Bristol-Myers Squibb; and receiving travel accommodations or expenses from Bayer Schering Pharma, Bristol-Myers Squibb, and Bayer. Dr Sullivan reports having research, consulting, or advisory roles with Bayer Corporation, Seattle Genetics, Incyte, and Novo Nordisk. Dr Lyman reported having educational programs or consulting roles with G1 Therapeutics, Partners Healthcare, BeyondSpring, Sandoz, Squibb, Merck, Jazz Pharm, Kallyope, TEVA, Seattle Genetics, and Samsung and receiving research funding from Amgen (to their institution). Dr Lyman reported receiving grants from Amgen (to their institution) and personal fees from Sandoz, G1 Therapeutics, Partners Healthcare, BeyondSpring, Squibb, Merck, Jazz, Samsung, Seattle Genetics, TEVA, and Fresenius outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Trial Participation Diagram

For the randomized sites, standing orders and system alerts recommended primary prophylactic colony-stimulating factor for all patients receiving chemotherapy regimens with a high risk of febrile neutropenia and no primary prophylactic colony-stimulating factor for patients receiving chemotherapy regimens with low risk of febrile neutropenia risk. Usual care had no modification to the existing chemotherapy order system at the site. Some patients who were lost to follow-up still had analyzable data that were submitted before they became lost to follow-up. These patients are included in the analysis section of the diagram. RT indicates radiation therapy. aOne additional site was allocated as a replacement for a previously randomized site that dropped out before receiving the intervention.

Figure 2.. Primary Prophylactic Colony-Stimulating Factor (PP-CSF) Use by Group and Febrile Neutropenia (FN) Risk Level

The bars indicate the percentage of patients using PP-CSF in each assigned treatment group by FN risk level. Error bars denote SEs. Differences in PP-CSF use between groups were not statistically significant after adjusting for covariates, in both the high-risk and low-risk groups.