Intervention Nonadherence in the TrACER (S1415CD) Study: A Pragmatic Randomized Trial of a Standardized Order Entry for CSF Prescribing.

Purpose: We conducted a pragmatic, cluster-randomized trial to test whether a guideline-based standing order entry (SOE) improves use of primary prophylactic CSF (PP-CSF) prescribing for patients receiving myelosuppressive chemotherapy. We investigated variability in adherence to the intervention.

Methods: We conducted a cluster-randomized trial among 32 oncology clinics from the NCI Community Oncology Research Program. Clinics were randomized 3:1 to a guideline-based PP-CSF SOE or usual care. Among SOE sites, automated orders for PP-CSF were included for regimens at high risk for febrile neutropenia (FN) and an alert not to use PP-CSF for low FN risk. A secondary 1:1 randomization was done among intervention sites to either SOE to prescribe or an alert to not prescribe PP-CSF for patients receiving intermediate risk-regimens. Providers were allowed to override the SOE.

Results: Overall, PP-CSF use among patients receiving high FN risk treatment was high and not different between arms; however, rates of PP-CSF use varied widely by site, ranging from 48.6% to 100%. Among those receiving low FN risk regimens, PP-CSF use was low and not different between arms; however, PP-CSF use ranged from 0% to 19.4% across sites. In the intermediate-risk substudy, PP-CSF was five-fold higher among sites randomized to SOE; however, there was considerable variability in adherence to intervention assignment: PP-CSF use ranged from 0% to 75% among sites randomized to SOE. Despite an alert to not prescribe, PP-CSF prescribing ranged from 0% to 33%.

Conclusion: In this randomized pragmatic trial aimed at improving PP-CSF prescribing, there was substantial variability in site adherence to the intervention assignment. Although the ability to opt out of the intervention is a feature of pragmatic trials, planning to estimate nonadherence is critical to ensure adequate power.