Development of Interoperable Computable Phenotype Algorithms for Adverse Events of Special Interest to Be Used for Biologics Safety Surveillance: Validation Study

Abstract

Background Adverse events associated with vaccination have been evaluated by epidemiological studies and more recently have gained additional attention with the emergency use authorization of several COVID-19 vaccines. As part of its responsibility to conduct postmarket surveillance, the US Food and Drug Administration continues to monitor several adverse events of special interest (AESIs) to ensure vaccine safety, including for COVID-19. Objective This study is part of the Biologics Effectiveness and Safety Initiative, which aims to improve the Food and Drug Administration’s postmarket surveillance capabilities while minimizing public burden. This study aimed to enhance active surveillance efforts through a rules-based, computable phenotype algorithm to identify 5 AESIs being monitored by the Center for Disease Control and Prevention for COVID-19 or other vaccines: anaphylaxis, Guillain-Barré syndrome, myocarditis/pericarditis, thrombosis with thrombocytopenia syndrome, and febrile seizure. This study examined whether these phenotypes have sufficiently high positive predictive value (PPV) to ensure that the cases selected for surveillance are reasonably likely to be a postbiologic adverse event. This allows patient privacy, and security concerns for the data sharing of patients who had nonadverse events can be properly accounted for when evaluating the cost-benefit aspect of our approach. Methods AESI phenotype algorithms were developed to apply to electronic health record data at health provider organizations across the country by querying for standard and interoperable codes. The codes queried in the rules represent symptoms, diagnoses, or treatments of the AESI sourced from published case definitions and input from clinicians. To validate the performance of the algorithms, we applied them to electronic health record data from a US academic health system and provided a sample of cases for clinicians to evaluate. Performance was assessed using PPV. Results With a PPV of 93.3%, our anaphylaxis algorithm performed the best. The PPVs for our febrile seizure, myocarditis/pericarditis, thrombocytopenia syndrome, and Guillain-Barré syndrome algorithms were 89%, 83.5%, 70.2%, and 47.2%, respectively. Conclusions Given our algorithm design and performance, our results support continued research into using interoperable algorithms for widespread AESI postmarket detection.