Considerations for practical use of tree-based scan statistics for signal detection using electronic healthcare data: a case study with insulin glargine.

Background: Hypothesis-free signal detection (HFSD) methods such as tree-based scan statistics (TBSS) applied to longitudinal electronic healthcare data (EHD) are increasingly used in safety monitoring. However, challenges may arise in interpreting HFSD results alongside results from disproportionality analysis of spontaneous reporting.

Research design and methods: Using the anti-diabetes drug insulin glargine (Lantus®) we apply two different tree-based scan designs using TreeScan™ software on retrospective EHD and compare the results to one another as well as to results from a disproportionality analysis using SRD.

Results: The self-controlled tree temporal scan method produced the larger number of alerts relative to propensity-score matched approach; however, far fewer alerts were observed when analyses were limited to EHD in inpatient/emergency room settings only. Very few reference adverse events were observed using TBSS methods on EHD relative to disproportionality methods in SRD.

Conclusion: Differences in detected alerts between TBSS methods and between TBSS and disproportionality analysis of SRD are likely attributable to differences in data, comparator, and study design. Our results suggest that HFDS methods like TBSS applied to EHD may complement more traditional approaches such as disproportionality analysis of SRD to provide a more complete picture of product safety in the post-approval setting.