Results Summary
What was the research about?
Some patients with cancer who receive chemotherapy get a serious health condition called febrile neutropenia, or FN. FN puts patients at risk for illness and death. Patients may be at high or low risk of FN, depending on the type of chemotherapy they receive. National guidelines say that doctors should prescribe a medicine called colony-stimulating factor, or CSF, for patients at high risk, but not for patients at low risk.
In this study, the research team wanted to help doctors at community cancer centers prescribe CSF based on guidelines. The team tested whether alerts in the patients’ health records increased doctors’ prescribing CSF for patients at high risk and not for patients at low risk. The team also looked at how many patients got FN.
What were the results?
For patients at high risk and low risk of FN, clinics with and without the alert didn’t differ in how doctors prescribed CSF or how many patients got FN after six months.
Who was in the study?
This study included 2,898 adult patients with breast, lung, or colorectal cancer. All were receiving their first cycle of chemotherapy at one of 32 community cancer clinics. Among patients, 79 percent were White, 12 percent were Black, 3 percent were Asian, and 2 percent were of another race; 13 percent were Hispanic. The average age was 58, and 77 percent were women.
What did the research team do?
The research team assigned the clinics by chance to the alert system or usual care. In the alert system, doctors received an alert to prescribe CSF for patients at high risk. For patients at low risk, they received an alert not to prescribe CSF. In usual care, doctors did not receive an alert and ordered CSF as they usually would.
At the end of the patients’ first chemotherapy treatment cycle and again six months later, the research team looked at data from patients’ health records.
Patients, doctors, pharmacists, and others gave input on the design of the study.
What were the limits of the study?
The study included patients with breast, lung, or colorectal cancer. Results may differ for people with other types of cancer.
Future research could look at other ways to reduce FN among patients with cancer.
How can people use the results?
Health systems can use these results when considering how to support doctors in following national guidelines for prescribing CSF.
Professional Abstract
Objective
To compare the effectiveness of a standing order for prescribing primary prophylactic colony-stimulating factors (PP-CSF) versus usual care on improving adherence to clinical practice prescription guidelines and rates of febrile neutropenia (FN) in patients receiving chemotherapy
Study Design
| Design Element | Description |
|---|---|
| Study Design | Pragmatic, prospective, cluster randomized trial |
| Population | 2,898 adult patients with breast, colorectal, or non-small cell lung cancer receiving their first cycle of chemotherapy associated with high or low risk for FN |
| Interventions/ Comparators |
|
| Outcomes |
Adherence to clinical practice PP-CSF prescription guidelines; incidence of FN within 6 months |
| Timeframe | Up to 6-month follow-up for study outcomes |
This pragmatic cluster randomized trial compared the effectiveness of a standing order entry intervention with usual care on adherence to clinical practice guidelines for PP-CSF prescription and patient rates of FN.
Researchers randomly assigned 32 community oncology practices to provide the standing order entry intervention or usual care.
- Standing order entry. When doctors ordered high-risk chemotherapy, the electronic medical records order system alerted doctors that PP-CSF was recommended for the patient. When doctors ordered low-risk chemotherapy, the system alerted doctors not to prescribe PP-CSF. Doctors could override the orders.
- Usual care. Doctors decided if they would prescribe PP-CSF for high- and low-risk chemotherapy as they usually would.
The study included 2,898 adult patients receiving chemotherapy for breast, colorectal, or non-small cell lung cancer. Of these patients, 79% were White, 12% were Black, 3% were Asian, and 2% were of another race; 13% were Hispanic. The average age was 58, and 77% were female.
Researchers reviewed electronic medical records at the end of the first chemotherapy treatment cycle to assess guideline adherence and FN incidence rates within six months.
Patients, clinicians, pharmacists, and clinical practice guideline group representatives provided input on study design, participant recruitment, and sharing results.
Results
Among high-risk and low-risk chemotherapy regimens, sites with and without a standing order did not differ significantly on PP-CSF prescriptions. For high-risk regimens, doctors prescribed PP-CSF for 89% of patients at sites with a standing order compared with 96% at sites providing usual care. For low-risk regimens, doctors prescribed PP-CSF for 6.8% of patients at sites with a standing order compared with 5.5% of patients at sites providing usual care.
FN rates did not differ significantly between sites with and without a standing order. FN rates were 6% or lower for both high- and low-risk regimens, which was less than anticipated.
Limitations
The study included patients with breast, lung, or colorectal cancer. Results may differ for people with other types of cancer.
Conclusions and Relevance
In this study, guideline-informed standing orders did not increase PP-CSF use in high-risk patients, nor did it decrease use in low-risk patients. These findings suggest that order entry systems may not affect CSF prescribing in community settings.
Future Research Needs
Future studies could continue to examine ways to reduce FN among patients with cancer.
Final Research Report
This project's final research report is expected to be available by May 2023.
Journal Citations
Results of This Project
Related Journal Citations
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- The reviewers pointed to the finding that passive automated alerts for physicians to prescribe primary prophylactic colony-stimulating factors (PP-CSF) decreased such prescribing for patients with intermediate risk for febrile neutropenia. They urged the researchers to consider this a positive finding given that trial outcomes did not indicate PP-CSF reduced risk for febrile neutropenia among cancer patients with intermediate risk. The researchers added language to the report’s discussion section about the possibility that in cases where there is clinical uncertainty about the usefulness of a particular treatment, automated alerts may be particularly helpful to prompt clinicians to follow clinical protocols.
- The reviewers noted that the use of PP-CSF presents a high financial cost and asked that the researchers address this cost in relation to their study findings. The researchers added language regarding the high cost of PP-CSF to the background and discussion sections of their report. In the discussion the researchers specifically considered potential cost savings of only using PP-CSF when empirical evidence demonstrated its clinical benefit.
- The reviewers asked whether the high baseline PP-CSF prescribing rates could have been affected by insurance coverage and specifically whether prior authorization for insurance coverage was necessary before the drug could be used. The researchers stated they did not track preauthorization requirements but they would assume that preauthorization was necessary given the high cost of the PP-CSF drug. The researchers agreed that high adherence to PP-CSF prescribing recommendations at baseline might have been affected by insurance companies’ growing stringency regarding requirements for preauthorization.