Sequential analysis for post-marketing drug safety surveillance using routinely collected electronic healthcare data:...

Routinely collected electronic healthcare data have created new opportunities for active, near real-time post-marketing drug safety surveillance. Sequential analysis offers a natural framework for periodic signal detection as data accrue and may facilitate earlier identification of emerging safety concerns. However, its application in drug safety surveillance has not been comprehensively characterized.

To systematically identify and characterize empirical applications and methodological developments of sequential analysis for safety signal detection in post-marketing drug surveillance using electronic healthcare data and to summarize key methodological approaches and evidence gaps in the literature.

Eligible studies included empirical observational studies that applied sequential analyses to periodically monitor prespecified drug-outcome pairs, and methodological studies that proposed or evaluated sequential approaches for post-marketing surveillance.

Six databases (PubMed, EMBASE, the Cochrane Library, CNKI, WanFang, and VIP) were searched from inception to 21 July 2025.

This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Two reviewers independently screened studies and extracted data using a standardized form. Findings were mapped to predefined analytical dimensions and synthesized narratively.

Forty-six studies were included, comprising 20 empirical observational studies and 26 methodological studies. All empirical studies were conducted in high-income countries, predominantly the United States, and 80% were pilot or feasibility assessments. Electronic health/medical records and administrative claims were the primary data sources. Considerable methodological heterogeneity was observed in study designs, analytical frequency, and sequential approaches. Two broad paradigms were identified: sequential testing and sequential risk estimation. Methodological studies were largely motivated by challenges inherent to observational settings, particularly confounding control.

Despite growing interest and methodological development, the application of sequential analysis in post-marketing drug safety surveillance remains limited. Future work should prioritize stronger approaches to confounding, clearer implementation standards, and better integration of sequential monitoring into routine pharmacovigilance practice.