Study of serious adverse drug reactions using FDA-approved drug labeling and MedDRA

Abstract

BackgroundAdverse Drug Reactions (ADRs) are of great public health concern. FDA-approved drug labeling summarizes ADRs of a drug product mainly in three sections, i.e., Boxed Warning (BW), Warnings and Precautions (WP), and Adverse Reactions (AR), where the severity of ADRs are intended to decrease in the order of BW > WP > AR. Several reported studies have extracted ADRs from labeling documents, but most, if not all, did not discriminate the severity of the ADRs by the different labeling sections. Such a practice could overstate or underestimate the impact of certain ADRs to the public health. In this study, we applied the Medical Dictionary for Regulatory Activities (MedDRA) to drug labeling and systematically analyzed and compared the ADRs from the three labeling sections with a specific emphasis on analyzing serious ADRs presented in BW, which is of most drug safety concern.ResultsThis study investigated New Drug Application (NDA) labeling documents for 1164 single-ingredient drugs using Oracle Text search to extract MedDRA terms. We found that only a small portion of MedDRA Preferred Terms (PTs), 3819 out of 21,920 or 17.42%, were observed in a whole set of documents. In detail, 466/3819 (12.0%) PTs were in BW, 2023/3819 (53.0%) were in WP, and 2961/3819 (77.5%) were in AR sections. We also found a higher overlap of top 20 occurring BW PTs with WP sections compared to AR sections. Within the MedDRA System Organ Class levels, serious ADRs (sADRs) from BW were prevalent in Nervous System disorders and Vascular disorders. A Hierarchical Cluster Analysis (HCA) revealed that drugs within the same therapeutic category shared the same ADR patterns in BW (e.g., nervous system drug class is highly associated with drug abuse terms such as dependence, substance abuse, and respiratory depression).ConclusionsThis study demonstrated that combining MedDRA standard terminologies with data mining techniques facilitated computer-aided ADR analysis of drug labeling. We also highlighted the importance of labeling sections that differ in seriousness and application in drug safety. Using sADRs primarily related to BW sections, we illustrated a prototype approach for computer-aided ADR monitoring and studies which can be applied to other public health documents.Electronic supplementary materialThe online version of this article (10.1186/s12859-019-2628-5) contains supplementary material, which is available to authorized users.

Quantifying the severity of adverse drug reactions using social media

“…We downloaded counts for the number of appearances of ADRs in the Boxed Warning section of drug labels from the supplement of Wu et al[24]. ADRs that appear on a drug label, based on their appearance in SIDER, that were not included in the list provided by Wu et al were considered to not have appeared in a Boxed Warning section [18].…”

Role of Pharmacogenetics in Adverse Drug Reactions: An Update towards Personalized Medicine

“…According to the Federal Drug Administration (FDA), ADR is "Any noxious, unintended and undesired effect of a drug, which occurs at doses used in humans for prophylaxis, diagnosis or therapy. This excludes therapeutic failures, intentional and accidental poisoning and drug abuse" (Wu et al, 2019). Besides, "adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related" (Sakaeda et al, 2013).…”

PRN Medicines Optimization and Nurse Education

“…Nevertheless, one third of all medication errors occur during medication administration [ 4 ]. Data from the European region show that the median percentages of hospital admissions due to ADRs and patients experiencing ADRs during hospitalization are 3.5% and 10.1%, respectively [ 9 ], and more serious ADRs often remain under-reported [ 10 , 11 ]. In healthcare systems, medication errors cause avoidable costs of between approximately €4.5 and 21.8 billion annually [ 12 ], and are important reasons for hospital admissions and mortality [ 13 ].…”