Currently submitted to: JMIR Human Factors
Date Submitted: Nov 28, 2025
Open Peer Review Period: Dec 4, 2025 - Jan 29, 2026
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Exploring Alert Fatigue, Mitigation Strategies, and Enhancing Drug-Drug Interaction Alert Acceptance: A Systematic Review and Meta-Analysis
ABSTRACT
Background:
Clinical decision support systems aim to reduce adverse drug events, particularly those arising from drug-drug interactions. However, poor user acceptance—often linked to alert fatigue—limits their clinical effectiveness and reduces patient safety.
Objective:
This systematic review examined the effect of alert fatigue on clinician acceptance of drug-drug interaction alerts, explored strategies to mitigate alert fatigue, and assessed associated clinical consequences.
Methods:
Five electronic databases were searched for studies reporting original data on clinician responses to drug-drug interaction alerts from clinical decision support systems. A meta-analysis estimated the pooled override rate, with subgroup analyses to explore heterogeneity.
Results:
Of 44 included studies, 25 (57%) reported on alert acceptance/override patterns and 18 (41%) on strategies to reduce alert fatigue. Only five studies (12%) assessed clinical outcomes. The overall drug-drug interaction alert override rate was 79.8% (95% CI: 73.0–86.7%), with individual study rates ranging from 55.4% to 95.7%. Inappropriately overridden alerts ranged from 3.2% to over 90%. The most common override reasons, such as "Will monitor", provided limited insight into alert fatigue. Common mitigation strategies included tailoring databases according to severity or clinical relevance and contextualising alerts based on patient-specific and/or laboratory data.
Conclusions:
Despite high override rates, consistent measures for alert fatigue were lacking. Inappropriate overrides without clinical justification pose patient safety risks, highlighting the need for standardised metrics. To meaningfully compare studies, a standardised definition for alert fatigue is required. We suggest a methodological framework to assist future studies reporting on alert fatigue. Clinical Trial: The protocol for this review was registered at PROSPERO (CRD42024541597).
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