Medication history-wide association studies for pharmacovigilance of pregnant patients

ABSTRACT:

Background

Systematic exclusion of pregnant people from interventional clinical trials has created a public health emergency for millions of patients through a dearth of robust safety data for common drugs.

Methods

We harnessed an enterprise collection of 2.8 M electronic health records (EHRs) from routine care, leveraging data linkages between mothers and their babies to detect drug safety signals in this population at full scale. Our mixed-methods signal detection approach stimulates new hypotheses for post-marketing surveillance agnostically of both drugs and diseases—by identifying 1,054 drugs historically prescribed to pregnant patients; developing a quantitative, medication history-wide association study; and integrating a qualitative evidence synthesis platform using expert clinician review for integration of biomedical specificity—to test the effects of maternal exposure to diverse drugs on the incidence of neurodevelopmental defects in their children.

Results

We replicated known teratogenic risks and existing knowledge on drug structure-related teratogenicity; we also highlight 5 common drug classes for which we believe this work warrants updated assessment of their safety.

Conclusion

Here, we present roots of an agile framework to guide enhanced medication regulations, as well as the ontological and analytical limitations that currently restrict the integration of real-world data into drug safety management during pregnancy. This research is not a replacement for inclusion of pregnant people in prospective clinical studies, but it presents a tractable team science approach to evaluating the utility of EHRs for new regulatory review programs—towards improving the delicate equipoise of accuracy and ethics in assessing drug safety in pregnancy. Plain language summary The exclusion of pregnant people during clinical drug development limits our understanding of drug safety in pregnancy. However, given that many approved medications are prescribed during pregnancy, we studied large sets of data from patient electronic medical records, including mother-baby pairs, to develop these drug safety insights. From 2.8 M medical records, we identified 1,054 drugs prescribed to pregnant patients. Combining computerized analysis with expert clinical review, we confirmed signals previously associated with neurodevelopmental defects in children born to drug-exposed mothers. We subsequently identified 5 commonly prescribed drug classes for which we believe this work warrants updated assessment of their safety. Our approach is not a replacement for inclusion of pregnant people in clinical trials but presents a new application of existing medical record data to improve the assessment of drug safety in pregnancy. Challa et al. used 2.8 million electronic health records for proactive pharmacovigilance program development, by rapidly generating and validating hypotheses between medication use during pregnancy and neonatal neurodevelopmental defects. They identify five drug classes for which deeper safety signal evaluation may improve product marketing.

SUBMITTER: Challa A 

PROVIDER: S-EPMC9481638 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature