ABSTRACT
INTRODUCTION: The US FDA receives more than 2 million postmarket reports each year. Safety Evaluators (SEs) review these reports, as well as external information, to identify potential safety signals. With the increasing number of reports and the size of external information, more efficient solutions for data integration and decision making are needed. OBJECTIVES: The aim of this study was to develop an interactive decision support application for drug safety surveillance that integrates and visualizes information from postmarket reports, product labels, and biomedical literature. METHODS: We conducted multiple meetings with a group of seven SEs at the FDA to collect the requirements for the Information Visualization Platform (InfoViP). Using infographic design principles, we implemented the InfoViP prototype version as a modern web application using the integrated information collected from the FDA Adverse Event Reporting System, the DailyMed repository, and PubMed. The same group of SEs evaluated the InfoViP prototype functionalities using a simple evaluation form and provided input for potential enhancements. RESULTS: The SEs described their workflows and overall expectations around the automation of time-consuming tasks, including the access to the visualization of external information. We developed a set of wireframes, shared them with the SEs, and finalized the InfoViP design. The InfoViP prototype architecture relied on a javascript and a python-based framework, as well as an existing tool for the processing of free-text information in all sources. This natural language processing tool supported multiple functionalities, especially the construction of time plots for individual postmarket reports and groups of reports. Overall, we received positive comments from the SEs during the InfoViP prototype evaluation and addressed their suggestions in the final version. CONCLUSIONS: The InfoViP system uses context-driven interactive visualizations and informatics tools to assist FDA SEs in synthesizing data from multiple sources for their case series analyses.
Subject(s)
Decision Support Techniques , Geographic Information Systems , Image Processing, Computer-Assisted , Product Surveillance, Postmarketing , Humans , Natural Language Processing , United States , United States Food and Drug AdministrationABSTRACT
Although current quetiapine labeling recommends that its dosage should be lowered 6-fold when coadministered with strong cytochrome P450 (CYP)3A inhibitors, a reported case of coma in a patient receiving quetiapine with lopinavir and ritonavir prompted the reevaluation of labeling recommendations for the dosing of quetiapine when coadministered with human immunodeficiency virus (HIV) protease inhibitors. Literature and database (FDA Adverse Event Reporting System and United States Symphony Health Solutions' Integrated Dataverse Database) searches allowed us to identify cases of coma and related adverse events involving the coadministration of quetiapine and HIV protease inhibitors and to estimate the frequency of concomitant use. Literature review and physiologically based pharmacokinetic modeling allowed us to estimate the potential for CYP3A inhibition to contribute to adverse events related to HIV protease inhibitor-quetiapine coadministration. We identified excess sedation following coadministration of quetiapine and an HIV protease inhibitor in 3 reports without obvious confounders. In prescription claims data, 0.4% of quetiapine patients were dispensed a concurrent ritonavir prescription. The quetiapine dose was not reduced on ritonavir initiation in 90% of therapy episodes. Available data indicate to us that all HIV protease inhibitors combined with ritonavir are likely to be strong CYP3A inhibitors. We predicted that ritonavir would increase quetiapine exposure comparable to the strong CYP3A inhibitor ketoconazole. The current dosing recommendations for use of quetiapine with strong CYP3A inhibitors (ie, 6-fold lower quetiapine dose) are appropriate and should be followed when quetiapine is coadministered with HIV protease inhibitors.
Subject(s)
HIV Protease Inhibitors/administration & dosage , Models, Biological , Quetiapine Fumarate/administration & dosage , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Antipsychotic Agents/pharmacokinetics , Cytochrome P-450 CYP3A Inhibitors/administration & dosage , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Cytochrome P-450 CYP3A Inhibitors/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Drug Labeling , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/pharmacology , Humans , Quetiapine Fumarate/adverse effects , Quetiapine Fumarate/pharmacokineticsABSTRACT
We reviewed Food and Drug Administration postmarketing reports of central nervous system (CNS) anticholinergic effects in association with oxybutynin. Taking domestic usage by age group into account, there is a disproportionately higher number of CNS adverse event cases reported in pediatric patients as compared with adult patients. CNS stimulation was prominent in the pediatric cases.
