Effectiveness of Interruptive Clinical Decision Support Alerts on Intravenous vs. Oral Acetaminophen Prescribing

Objective: Intravenous (IV) and oral (PO) acetaminophen have equivalent bioavailability and effectiveness, but IV formulations are significantly more expensive. Clinical decision support (CDS) tools can encourage cost-effective prescribing. We evaluated the effectiveness and acceptability of different CDS strategies on prescribing patterns of acetaminophen. Methods: We conducted a two-arm randomized controlled trial with a historical comparator at our academic medical center, including 23,676 acetaminophen orders for 13,139 adult inpatients between July 2023 and November 2024. In the pre-intervention period, providers received a single-click interruptive alert when ordering IV acetaminophen. In the post-period, providers were randomized to either a multi-click interruptive alert or no alert. The primary outcome was alert effectiveness; secondary outcomes included acceptability and durability. Results: The mean patient age was 57 years; 64% were female, 62% white, and 87% English-speaking. Most orders were placed for medicine (32%) primarily by residents (61%). Pre-intervention, 9.4% of orders were for IV acetaminophen, compared to 11.2% in the multi-click interruptive group and 12.1% in controls (p=0.153). Among 624 interruptive alerts followed by orders, 24.5% switched to PO. Interrupted time series analysis showed no significant change in IV order trends. Conclusions: Approximately one-quarter of multi-click alerts prompted a switch to PO acetaminophen, but overall effectiveness was no greater than the control or single-click alert. Findings suggest that increasing alert disruptiveness may add cognitive burden without meaningful gains in effectiveness. A multi-click interruptive alert did not significantly change IV acetaminophen prescribing. Effective CDS strategies may require minimally disruptive designs integrated with education. Keywords: Clinical Decision Support; Acetaminophen; Electronic Health Records and Systems; Drug Cost; Cognitive Workload