Triple challenges - Small sample size in both exposure and control groups to scan rare maternal outcomes in a signal identification approach: A simulation study.

View Abstract

There is a dearth of safety data on maternal outcomes after perinatal medication exposure. Data-mining for unexpected adverse event occurrence in existing datasets is a potentially useful approach. One method, the Poisson tree-based scan statistic (TBSS), assumes that the expected outcome counts, based on incidence of outcomes in the control group, are estimated without error. This assumption may be difficult to satisfy with a small control group. Our simulation study evaluated the effect of imprecise incidence proportions from the control group on TBSS' ability to identify maternal outcomes in pregnancy research. We simulated base case analyses with "true" expected incidence proportions and compared these to imprecise incidence proportions derived from sparse control samples. We varied parameters impacting Type I error and statistical power (exposure group size, outcome's incidence proportion, and effect size). We found that imprecise incidence proportions generated by a small control group resulted in inaccurate alerting, inflation of Type I error, and removal of very rare outcomes for TBSS analysis due to "zero" background counts. Ideally, the control size should be at least several times larger than the exposure size to limit the number of false positive alerts and retain statistical power for true alerts.

Investigators
Abbreviation
Am J Epidemiol
Publication Date
2024-06-24
Pubmed ID
38918039
Medium
Print-Electronic
Full Title
Triple challenges - Small sample size in both exposure and control groups to scan rare maternal outcomes in a signal identification approach: A simulation study.
Authors
Thai TN, Winterstein AG, Suarez EA, He J, Zhao Y, Zhang D, Stojanovic D, Liedtka J, Anderson A, Hernández-Muñoz JJ, Munoz M, Liu W, Dashevsky I, Messenger-Jones E, Siranosian E, Maro JC